TY  - JOUR
AB  - Historically, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) was thought to be the key enzyme responsible for testicular testosterone production. In humans, loss-of-function mutations in HSD17B3 impair testosterone production during prenatal life leading to impaired development of androgen-dependent tissues in 46,XY individuals. However, male mice with HSD17B3 deficiency exhibit normal testicular testosterone concentrations, normal development of reproductive organs and are fertile, suggesting that mice express other hydroxysteroid dehydrogenase enzymes capable of testicular testosterone synthesis. This study aimed to investigate whether 17β-hydroxysteroid dehydrogenase type 12 (HSD17B12), which can convert androstenedione to testosterone in mice but not in humans, compensates for the lack of HSD17B3 in Hsd17b3 knockout (KO) mice. We used CRISPR/Cas9 to substitute the amino acid in mouse HSD17B12 that is responsible for its ability to convert androstenedione to testosterone with the amino acid of the human enzyme that prevents androstenedione being used as a substrate. When this Hsd17b12 mutation was introduced into Hsd17b3 KO mice, males exhibited normal reproductive tracts but reduced testicular testosterone production with a consequential reduction in seminal vesicle weight. This suggests HSD17B12 contributes toward testosterone production in the absence of HSD17B3, but other enzymes must also contribute. We therefore quantified other testicular hydroxysteroid dehydrogenases, finding that HSD17B7 mRNA and protein was markedly upregulated in Hsd17b3 KO testes. We confirmed that mouse, but not human, HSD17B7 can produce testosterone in vitro. We conclude that compared to humans, mice exhibit increased plasticity in testosterone production via hydroxysteroid dehydrogenase enzymes to support androgen action and male fertility.
AU  - Lawrence, B.M.*
AU  - O'Donnell, L.*
AU  - Gannon, A.L.*
AU  - Skerrett-Byrne, D.A.
AU  - Parameswaran, S.*
AU  - Abbott, I.*
AU  - Smith, S.*
AU  - Handelsman, D.J.*
AU  - Rebourcet, D.*
AU  - Smith, L.B.*
C1  - 74332
C2  - 57466
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Functional analysis of HSD17B3-deficient male mice reveals roles for HSD17B7 and HSD17B12 in testosterone biosynthesis.
JO  - Endocrinology
VL  - 166
IS  - 6
PB  - Endocrine Soc
PY  - 2025
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Thyroid hormone (TH) effects are mediated through TH receptors (TRs) TRα1, TRβ1, and TRβ2. The TRs bind to the DNA and regulate expression of TH target genes (canonical signaling). In addition, they mediate activation of signaling pathways (noncanonical signaling). Whether noncanonical TR action contributes to the spectrum of TH effects is largely unknown. Aim of this study was to attribute physiological effects to the TR isoforms and their canonical and noncanonical signaling. We conducted multi-parameter phenotyping in male and female TR knockout mice (TRαKO, TRβKO), mice with disrupted canonical signaling due to mutations in the TR DNA-binding domain (TRαGS, TRβGS) and their wild-type littermates. Perturbations in senses, especially hearing (mainly TRβ with a lesser impact of TRα), visual acuity, retinal thickness (TRα and TRβ) and in muscle metabolism (TRα) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization or increased anxiety related behavior were only observed in TRαKO, but not TRαGS mice. Noncanonical TRα action improved energy utilization and prevented hyperphagia observed in female TRαKO mice. In summary, by examining the phenotypes of TRα and TRβ knockout models alongside their DNA-binding-deficient mutants and wild-type counterparts, we could establish that the noncanonical actions of TRα and TRβ play a crucial role in modulating sensory, behavioral, and metabolic functions and, thus, contribute to the spectrum of physiological TH effects.
AU  - Hönes, G.S.*
AU  - Geist, D.*
AU  - Wenzek, C.*
AU  - Pfluger, P.T.
AU  - Müller, T.D.
AU  - Aguilar-Pimentel, J.A.
AU  - Amarie, O.V.
AU  - Becker, L.
AU  - Dragano, N.R.V.
AU  - Garrett, L.
AU  - Hölter, S.M.
AU  - Rathkolb, B.
AU  - Rozman, J.
AU  - Spielmann, N.
AU  - Treise, I.
AU  - Wolf, E.*
AU  - Wurst, W.
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Hrabě de Angelis, M.
AU  - Führer, D.*
AU  - Moeller, L.C.*
C1  - 70869
C2  - 55829
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Comparative phenotyping of mice reveals canonical and noncanonical physiological functions of TRα and TRβ.
JO  - Endocrinology
VL  - 165
IS  - 8
PB  - Endocrine Soc
PY  - 2024
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Thyroid hormone increases energy expenditure. Its action is mediated by TR, nuclear receptors present in peripheral tissues and in the central nervous system, particularly in hypothalamic neurons. Here, we address the importance of thyroid hormone signaling in neurons, in general for the regulation of energy expenditure. We generated mice devoid of functional TR in neurons using the Cre/LoxP system. In hypothalamus, which is the center for metabolic regulation, mutations were present in 20 to 42% of the neurons. Phenotyping was performed under physiological conditions that trigger adaptive thermogenesis: cold and high fat diet (HFD) feeding. Mutant mice displayed impaired thermogenic potential in brown and inguinal white adipose tissues and were more prone to diet-induced obesity. They showed a decreased energy expenditure on chow diet, and gain more weight on HFD. This higher sensitivity to obesity disappeared at thermoneutrality. Concomitantly, the AMPK pathway was activated in the ventromedial Hypothalamus (VMH) of the mutants as compared to the controls. In agreement sympathetic nervous system (SNS) output, visualized by tyrosine hydroxylase expression was lower in the brown adipose tissue (BAT) of the mutants. In contrast, absence of TR signaling in the mutants did not affect their ability to respond to cold exposure. This study provides the first genetic evidence that thyroid hormone signaling exerts a significant influence in neurons to stimulate energy expenditure in some physiological context of adaptive thermogenesis. TR function in neurons to limit weight gain in response to HFD and this effect is associated with a potentiation of SNS output.
AU  - Rial-Pensado, E.*
AU  - Canaple, L.*
AU  - Guyot, R.*
AU  - Clemmensen, C.
AU  - Wiersema, J.*
AU  - Wu, S.*
AU  - Richard, S.*
AU  - Boelen, A.*
AU  - Müller, T.D.
AU  - López, M.*
AU  - Flamant, F.*
AU  - Gauthier, K.*
C1  - 67460
C2  - 54116
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Neuronal blockade of thyroid hormone signaling increases sensitivity to diet-induced obesity in adult male mice.
JO  - Endocrinology
VL  - 164
IS  - 4
PB  - Endocrine Soc
PY  - 2023
SN  - 0013-7227
ER  - 

TY  - BOOK
AB  - Multiple endocrine neoplasia (MEN) indicates a
       group of familial syndromes characterized by the simultaneous 
      occurrence of tumors in more than one endocrine organ. MEN patients 
      develop tumors of the pancreas, parathyroid, pituitary, adrenal, and 
      thyroid glands, together with various neuroendocrine tumors (NETs) of 
      the respiratory and gastrointestinal tracts. These syndromes are 
      inherited as autosomal dominant traits with high penetrance. There are 
      three recognized MEN syndromes: MEN type 1 (MEN1), MEN2, and MEN4. Each 
      of these syndromes has a specific tumor spectrum and is caused by 
      germline mutation of a different gene: MEN1 patients carry 
      loss-of-function mutations in the MEN1 tumor suppressor gene; MEN2 is associated with activating changes in the RET proto-oncogene; and MEN4 is caused by mutations in CDKN1B encoding the cell cycle inhibitor p27Kip1 (p27).MEN4 is the most recently discovered syndrome. CDKN1B
       was identified as susceptibility gene for multiple endocrine tumors 
      based on studies of a rat strain displaying a MEN1-like tumors spectrum 
      (MENX syndrome). MENX-affected rats were found to carry a spontaneous 
      germline inactivating mutation in Cdkn1b. To date only 19 patients with germline CDKN1B
       mutations have been reported in the literature. The most recurrent 
      MEN4-associated clinical manifestations are primary hyperparathyroidism 
      (1°HPT) and pituitary adenomas. MENX and MEN4 syndromes mostly resemble 
      MEN1; hence they were initially referred to as MEN1-like. This review 
      will focus on the phenotypic features and the genetics of MENX and MEN4 
      syndromes and will briefly address the role of CDKN1B in tumorigenesis.
AU  - Minaskan Karabid, N.
AU  - Pellegata, N.S.
C1  - 64451
C2  - 51854
SP  - 245-274
TI  - Multiple endocrine neoplasia-type 4 (MEN4) and other MEN1-like syndromes.
JO  - Endocrinology
PY  - 2021
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Type 1 diabetes mellitus (T1DM) is associated with impaired spermatogenesis, lower testosterone levels and epididymal weight. However, the underlying processes in the testis are unknown and remain to be elucidated. Therefore, the present study focused on the effects of T1DM on testicular function in a spontaneously diabetic rat model.BB/OKL rats after diabetes manifestation were divided into three groups: without insulin treatment, insulin treatment for a duration of 2 and of 6 weeks. Anthropometrical data, circulating levels of gonadotrophins, testosterone and inhibin B were measured. Intratesticular testosterone, oxidative stress, inflammation, and apoptosis were analyzed. Key enzymes of steroidogenesis were evaluated in the testis.Untreated diabetic rats had significantly lower serum FSH and LH levels. Serum and intratesticular testosterone levels significantly decreased in the untreated diabetic rat compared to healthy controls. Key markers of Leydig cell function were significantly downregulated on RNA level: Insl3 by 53% (p=0.006), Star by 51% (p=0.004), Cyp11A1 by 80% (p=0.003), 3Beta-Hsd2 by 61% (p=0.005) and Pbr by 52% (p=0.002). In the insulin-treated group only Cyp11A1 and 3Beta-Hsd2 transcripts were significantly lower. Interestingly the long-term insulin treated group showed significant upregulation of most steroidogenic enzymes without affecting testosterone levels. TNF-alpha and apoptosis were significantly increased in the long-term insulin treated rats. In conclusion T1DM, with a severe lack of insulin, has an adverse action on Leydig cell function. This is partially reversible with well compensated blood glucose control. Long-term T1DM adversely affects Leydig cell function due to the process of inflammation and apoptosis.
AU  - Wagner, I.V.*
AU  - Klöting, N.
AU  - Savchuk, I.*
AU  - Eifler, L.*
AU  - Kulle, A.*
AU  - Kralisch-Jäcklein, S.*
AU  - Dötsch, J.*
AU  - Hiort, O.*
AU  - Svechnikov, K.*
AU  - Söder, O.*
C1  - 61205
C2  - 50096
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Diabetes type 1 negatively influences Leydig cell function in rats which is partially reversible by insulin treatment.
JO  - Endocrinology
VL  - 162
IS  - 4
PB  - Endocrine Soc
PY  - 2021
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n =28) and without (n =30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T 4, T 3, and rT 3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T 4, T 3, and rT 3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T 4 was inversely associated with BDEs 99, 100, Σ PBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T 3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT 3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, Σ OTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.
AU  - Li, Z.M.
AU  - Hernandez-Moreno, D.
AU  - Main, K.M.*
AU  - Skakkebæk, N.E.*
AU  - Kiviranta, H.*
AU  - Toppari, J.*
AU  - Feldt-Rasmussen, U.*
AU  - Shen, H.*
AU  - Schramm, K.-W.
AU  - de Angelis, M.
C1  - 54038
C2  - 45224
SP  - 3473-3481
TI  - Association of in utero persistent organic pollutant exposure with placental thyroid hormones.
JO  - Endocrinology
VL  - 159
IS  - 10
PY  - 2018
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Endocrine Society. In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual’s nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect.
AU  - Ryan, K.K.*
AU  - Packard, A.E.B.*
AU  - Larson, K.R.*
AU  - Stout, J.*
AU  - Fourman, S.M.*
AU  - Thompson, A.M.K.*
AU  - Ludwick, K.*
AU  - Habegger, K.M.*
AU  - Stemmer, K.
AU  - Itoh, N.*
AU  - Perez-Tilve, D.*
AU  - Tschöp, M.H.
AU  - Seeley, R.J.*
AU  - Ulrich-Lai, Y.M.*
C1  - 52228
C2  - 43855
CY  - Cary
SP  - 400-413
TI  - Dietary manipulations that induce ketosis activate the HPA axis in male rats and mice: A potential role for fibroblast growth factor-21.
JO  - Endocrinology
VL  - 159
IS  - 1
PB  - Oxford Univ Press Inc
PY  - 2018
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - It is undeniably one of the greatest findings in biology that (with some very minor exceptions) every cell in the body possesses the whole genetic information needed to generate a complete individual. Today, this concept has been so thoroughly assimilated that we struggle to still see how surprising this finding actually was: all cellular phenotypes naturally occurring in one person are generated from genetic uniformity, and thus are per definition epigenetic. Transcriptional mechanisms are clearly critical for developing and protecting cell identities, because a mis-expression of few or even single genes can efficiently induce inappropriate cellular programmes. However, how transcriptional activities are molecularly controlled and which of the many known epigenomic features have causal roles remains unclear. Today, clarification of this issue is more pressing than ever because profiling efforts and epigenome-wide association studies (EWAS) continuously provide comprehensive datasets depicting epigenomic differences between tissues and disease states. In this commentary, we propagate the idea of a widespread follow-up use of epigenome editing technology in EWAS studies. This would enable them to address the questions of which features, where in the genome, and which circumstances are essential to shape development and trigger disease states.
AU  - Sun, N.
AU  - Wu, Y.
AU  - Nanba, K.*
AU  - Sbiera, S.*
AU  - Kircher, S.*
AU  - Kunzke, T.
AU  - Aichler, M.
AU  - Berezowska, S.*
AU  - Reibetanz, J.*
AU  - Rainey, W.E.*
AU  - Fassnacht, M.*
AU  - Walch, A.K.
AU  - Kroiss, M.*
C1  - 52854
C2  - 44285
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
SP  - 1511-1524
TI  - High resolution tissue mass spectrometry imaging reveals a refined functional anatomy of the human adult adrenal gland.
JO  - Endocrinology
VL  - 159
IS  - 3
PB  - Royal Soc
PY  - 2018
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - slet cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intra-islet vascularization and paracrine cell signaling are mostly based on rodent pancreas. We here assessed for the first time the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared pancreas tissue slices of fresh tissue obtained from non-diabetic patients undergoing partial pancreatectomy. In addition, we transplanted human donor islets into the anterior chamber of the mouse eye. Next, we performed three-dimensional in situ and in vivo imaging of islet cell and vessel architecture at cellular resolution and compared our findings to mouse and porcine islets. Our data reveal a significantly different vascular architecture with decreased vessel diameter, reduced vessel branching and shortened total vessel network in human compared to mouse islets. Together with the distinct cellular arrangement in human islets this limits beta-endothelial cell interactions, facilitates connection of alpha and beta cells and promotes the formation of independent beta cell clusters within islets. Furthermore, our results show that the endogenous vascular network of islets is significantly altered after transplantation in a donor-age related mechanism. Thus, our study provides new insight into vascular architecture and cellular arrangement of human islets with apparent consequences for intercellular islet signaling. Moreover, our findings suggest that human islet engraftment after transplantation can be improved by the use of alternative, less mature islet cell sources.
AU  - Cohrs, C.M.
AU  - Chen, C.
AU  - Jahn, S.
AU  - Stertmann, J.
AU  - Chmelova, H.
AU  - Weitz, J.*
AU  - Bähr, A.*
AU  - Klymiuk, N.*
AU  - Steffen, A.
AU  - Ludwig, B.
AU  - Kamvissi, V.*
AU  - Wolf, E.*
AU  - Bornstein, S.R.
AU  - Solimena, M.
AU  - Speier, S.
C1  - 50572
C2  - 42364
CY  - Washington
SP  - 1-13
TI  - Vessel network architecture of adult human islets promotes distinct cell-cell interactions in situ and is altered after transplantation.
JO  - Endocrinology
VL  - 158
IS  - 4
PB  - Endocrine Soc
PY  - 2017
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - The HSD17B12 gene belongs to the hydroxysteroid (17β) dehydrogenase superfamily, and it has been implicated in the conversion of estrone to estradiol as well as in the synthesis of arachidonic acid (AA). AA is a precursor of prostaglandins, which are involved in the regulation of female reproduction, prompting us to study the role of HSD17B12 enzyme in the ovarian function. We found a broad expression of HSD17B12 enzyme in both human and mouse ovaries. The enzyme was localized in the theca interna, corpus luteum, granulosa cells, oocytes and surface epithelium. Interestingly, haploinsufficiency of the HSD17B12 gene in female mice resulted in subfertility, indicating an important role for HSD17B12 enzyme in the ovarian function. In line with significantly increased length of the diestrus phase, the HSD17B(+/-) females gave birth less frequently than WT females, and the litter size of HSD17B12(+/-) females was significantly reduced. Interestingly, we observed meiotic spindle formation in immature follicles, suggesting defective meiotic arrest in HSD17B12(+/-) ovaries. The finding was further supported by transcriptome analysis showing differential expression of several genes related to the meiosis. In addition, polyovular follicles and oocytes trapped inside the corpus luteum were observed, indicating a failure in the oogenesis and ovulation, respectively. Intraovarian concentrations of steroid hormones were normal in HSD17B12(+/-) females, whereas the levels of AA and its metabolites (6-keto PGT1a, PGD2, PGE2, PGF2alfa and TXB2) were decreased. In conclusion, our study demonstrates that HSD17B12 enzyme plays an important role in female fertility through its role in AA metabolism.
AU  - Kemiläinen, H.*
AU  - Adam, M.*
AU  - Mäki-Jouppila, J.*
AU  - Damdimopoulou, P.*
AU  - Damdimopoulos, A.E.*
AU  - Kere, J.*
AU  - Hovatta, O.*
AU  - Laajala, T.D.*
AU  - Aittokallio, T.*
AU  - Adamski, J.
AU  - Ryberg, H.*
AU  - Ohlsson, C.*
AU  - Strauss, L.*
AU  - Poutanen, M.*
C1  - 49297
C2  - 41723
CY  - Washington
SP  - 3719-3730
TI  - The hydroxysteroid (17β) dehydrogenase family gene HSD17B12 is involved in the prostaglandin synthesis pathway, the ovarian function, and regulation of fertility.
JO  - Endocrinology
VL  - 157
IS  - 10
PB  - Endocrine Soc
PY  - 2016
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Pheochromocytomas (PCCs) are tumors arising from neural crest-derived chromaffin cells. There are currently few animal models of PCC that recapitulate the key features of human tumors. Since such models may be useful for investigations of molecular pathomechanisms and development of novel therapeutic interventions, we characterized a spontaneous animal model (MENX rats) that develops endogenous PCCs with complete penetrance. Urine was longitudinally collected from wild-type (wt) and MENX-affected (mutant) rats and outputs of catecholamines and their O-methylated metabolites determined by mass spectrometry. Adrenal catecholamine contents, cellular ultrastructure and expression of phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine, were also determined in wt and mutant rats. Blood pressure was longitudinally measured and end-organ pathology assessed. Compared to wt rats, mutant animals showed age-dependent increases in urinary outputs of norepinephrine (P=0.0079) and normetanephrine (P=0.0014) that correlated in time with development of tumor nodules, increases in blood pressure and development of hypertension-related end-organ pathology. Development of tumor nodules, which lacked expression of PNMT, occurred on a background of adrenal medullary morphological and biochemical changes occurring as early as 1 month of age and involving increased adrenal medullary concentrations of dense cored vesicles, tissue contents of both norepinephrine and epinephrine and urinary outputs of metanephrine, the metabolite of epinephrine. Taken together, MENX-affected rats share several biochemical and pathophysiological features with PCC patients. This model thus provides a suitable platform to study the pathogenesis of PCC for preclinical translational studies aimed at development of novel therapies for aggressive forms of human tumors.
AU  - Wiedemann, T.
AU  - Peitzsch, M.*
AU  - Qin, N.*
AU  - Neff, F.
AU  - Ehrhart-Bornstein, M.*
AU  - Eisenhofer, G.*
AU  - Pellegata, N.S.
C1  - 48730
C2  - 41293
CY  - Washington
SP  - 3157-3166
TI  - Morphology, biochemistry and pathophysiology of MENX-related pheochromocytoma recapitulate the clinical features.
JO  - Endocrinology
VL  - 157
IS  - 8
PB  - Endocrine Soc
PY  - 2016
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.
AU  - Reis, W.L.*
AU  - Yi, C.-X.
AU  - Gao, Y.
AU  - Tschöp, M.H.
AU  - Stern, J.E.*
C1  - 44017
C2  - 36699
CY  - Washington
SP  - 1303-1315
TI  - Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior.
JO  - Endocrinology
VL  - 156
IS  - 4
PB  - Endocrine Soc
PY  - 2015
SN  - 0013-7227
ER  - 

TY  - JOUR
AU  - Lee, M.S.
AU  - Pellegata, N.S.
C1  - 23725
C2  - 31258
SP  - 1387-1389
TI  - Folate receptor-mediated drug targeting: A possible strategy for nonfunctioning pituitary adenomas?
JO  - Endocrinology
VL  - 154
IS  - 4
PB  - Endocrine Society
PY  - 2013
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - The most effective treatment for obesity is bariatric surgery. However, there is increasing concern that bariatric surgery can cause nutrient deficiencies that translate into metabolic bone disease. Whether this is true for all surgery types is not yet clear. We therefore investigated the effects of 2 commonly applied bariatric surgeries (Roux-en-Y gastric bypass [RYGB] and vertical sleeve gastrectomy) on energy and bone metabolism in rats 60 days after surgery. Both surgeries resulted in similar reductions of body weight, body fat, and food intake. Glucose tolerance was improved to a similar extent after both surgeries and was accompanied by increased postprandial secretion of glucose-dependent insulinotropic peptide. Using microcomputed tomography, we found that, relative to sham-operated rats, bone volume was significantly reduced after RYGB but not vertical sleeve gastrectomy. RYGB rats also had markedly reduced lipid absorption from the intestine and significantly lower serum 25-hydroxyvitamin D and calcium levels. Importantly, dietary supplementation with calcium and vitamin D could not fully rescue the reduced bone volume after RYGB surgery. Both surgeries resulted in a significant increase in stomach pH, which may have worsened the malabsorption in RYGB rats. Our findings suggest that bone loss in RYGB rats is not exclusively driven by calcium and vitamin D malabsorption but also by additional factors that may not be rescuable by dietary supplementation. These data point toward important similarities and differences between bariatric procedures that should be considered in clinical settings as guidance for which procedure will be best for specific patient populations.
AU  - Stemmer, K.
AU  - Bielohuby, M.*
AU  - Grayson, B.E.*
AU  - Begg, D.P.*
AU  - Chambers, A.P.*
AU  - Neff, C.
AU  - Woods, S.C.*
AU  - Erben, R.G.*
AU  - Tschöp, M.H.
AU  - Bidlingmaier, M.*
AU  - Clemens, T.L.*
AU  - Seeley, R.J.*
C1  - 25151
C2  - 31832
SP  - 2015-2024
TI  - Roux-en-Y gastric bypass surgery but not vertical sleeve gastrectomy decreases bone mass in male rats.
JO  - Endocrinology
VL  - 154
IS  - 6
PB  - Endocrine Soc.
PY  - 2013
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Ghrelin is a gastrointestinal polypeptide that acts through the ghrelin receptor (GHSR) to promote food intake and increase adiposity. Activation of GHSR requires the presence of a fatty-acid (FA) side chain on amino acid residue serine 3 of the ghrelin molecule. However, little is known about the role that the type of FA used for acylation plays in the biological action of ghrelin. We therefore evaluated a series of differentially acylated peptides to determine whether alterations in length or stability of the FA side chain have an impact on the ability of ghrelin to activate GHSR in vitro or to differentially alter food intake, body weight, and body composition in vivo. Fatty acids principally available in the diet (such as palmitate C16) and therefore representing potential substrates for the ghrelin-activating enzyme ghrelin O-acyltransferase (GOAT) were used for dose-, time-, and administration/route-dependent effects of ghrelin on food intake, body weight, and body composition in rats and mice. Our data demonstrate that altering the length of the FA side chain of ghrelin results in the differential activation of GHSR. Additionally, we found that acylation of ghrelin with a long-chain FA (C16) delays the acute central stimulation of food intake. Lastly, we found that, depending on acylation length, systemic and central chronic actions of ghrelin on adiposity can be enhanced or reduced. Together our data suggest that modification of the FA side-chain length can be a novel approach to modulate the efficacy of pharmacologically administered ghrelin.
AU  - Heppner, K.M.*
AU  - Chaudhary, N.*
AU  - Müller, T.D.
AU  - Kirchner, H.*
AU  - Habegger, K.M.*
AU  - Ottaway, N.*
AU  - Smiley, D.L.*
AU  - DiMarchi, R.*
AU  - Hofmann, S.M.
AU  - Woods, S.C.*
AU  - Sivertsen, B.*
AU  - Holst, B.*
AU  - Pfluger, P.T.*
AU  - Perez-Tilve, D.*
AU  - Tschöp, M.H.
C1  - 10521
C2  - 30309
SP  - 4687-4695
TI  - Acylation type determines ghrelin's effects on energy homeostasis in rodents.
JO  - Endocrinology
VL  - 153
IS  - 10
PB  - Endocrine Society
PY  - 2012
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Dysregulation of fatty acid oxidation plays a pivotal role in the pathophysiology of obesity and insulin resistance. Medium- and short-chain-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (SCHAD) (gene name, hadh) catalyze the third reaction of the mitochondrial β-oxidation cascade, the oxidation of 3-hydroxyacyl-CoA to 3-ketoacyl-CoA, for medium- and short-chain fatty acids. We identified hadh as a putative obesity gene by comparison of two genome-wide scans, a quantitative trait locus analysis previously performed in the polygenic obese New Zealand obese mouse and an earlier described small interfering RNA-mediated mutagenesis in Caenorhabditis elegans. In the present study, we show that mice lacking SCHAD (hadh(-/-)) displayed a lower body weight and a reduced fat mass in comparison with hadh(+/+) mice under high-fat diet conditions, presumably due to an impaired fuel efficiency, the loss of acylcarnitines via the urine, and increased body temperature. Food intake, total energy expenditure, and locomotor activity were not altered in knockout mice. Hadh(-/-) mice exhibited normal fat tolerance at 20 C. However, during cold exposure, knockout mice were unable to clear triglycerides from the plasma and to maintain their normal body temperature, indicating that SCHAD plays an important role in adaptive thermogenesis. Blood glucose concentrations in the fasted and postprandial state were significantly lower in hadh(-/-) mice, whereas insulin levels were elevated. Accordingly, insulin secretion in response to glucose and glucose plus palmitate was elevated in isolated islets of knockout mice. Therefore, our data indicate that SCHAD is involved in thermogenesis, in the maintenance of body weight, and in the regulation of nutrient-stimulated insulin secretion.
AU  - Schulz, N.*
AU  - Himmelbauer, H.*
AU  - Rath, M.*
AU  - van Weeghel, M.*
AU  - Houten, S.*
AU  - Kulik, W.*
AU  - Suhre, K.
AU  - Scherneck, S.*
AU  - Vogel, H.*
AU  - Kluge, R.*
AU  - Wiedmer, P.*
AU  - Joost, H.G.*
AU  - Schürmann, A.*
C1  - 6812
C2  - 29307
SP  - 4641-4651
TI  - Role of medium- and short-chain L-3-hydroxyacyl-CoA dehydrogenase in the regulation of body weight and thermogenesis.
JO  - Endocrinology
VL  - 152
IS  - 12
PB  - Endocrine Soc.
PY  - 2011
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Primary aldosteronism is considered to be responsible for almost 10% of all cases of arterial hypertension. The genetic background of this common disease, however, has been elucidated only for the rare familial types, whereas in the large majority of sporadic cases, underlying mechanisms still remain unclear. In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism, a mutagenesis screen after treatment of mice with the alkylating agent N-ethyl-N-nitrosourea was established for the parameter aldosterone. As the detection method we used a time-resolved fluorescence immunoassay that allows the measurement of aldosterone in very small murine sample volumes. Based on this assay, we first determined the normal aldosterone values for wild-type C3HeB/FeJ mice under baseline conditions [92 ± 6 pg/ml for females (n = 69) and 173 ± 16 pg/ml for males (n = 55)]. Subsequently, aldosterone measurement was carried out in more than 2800 F(1) offspring of chemically mutagenized C3HeB/FeJ mice, and values were compared with aldosterone levels from untreated animals. Persistent hyperaldosteronism (defined as levels +3 sd above the mean of untreated animals) upon repeated measurements was present in seven female and two male F(1) offspring. Further breeding of these founders gave rise to F(2) pedigrees from which eight lines with different patterns of inheritance of hyperaldosteronism could be established. These animals will serve for detailed phenotypic and genetic characterization in the future. Taken together, our data demonstrate the feasibility of a phenotype-driven mutagenesis screen to detect and establish mutant mouse lines with a phenotype of chronic hyperaldosteronism.
AU  - Spyroglou, A.*
AU  - Wagner, S.
AU  - Gomez-Sanchez, C.*
AU  - Rathkolb, B.
AU  - Wolf, E.
AU  - Manolopoulou, J.*
AU  - Reincke, M.*
AU  - Bidlingmaier, M.*
AU  - Hrabě de Angelis, M.
AU  - Beuschlein, F.*
C1  - 4391
C2  - 28405
SP  - 326-331
TI  - Utilization of a mutagenesis screen to generate mouse models of hyperaldosteronism.
JO  - Endocrinology
VL  - 152
IS  - 1
PB  - Springfield, Ill.
PY  - 2011
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Multiple reports implicated the function of G protein-coupled receptor (GPR)-30 with nongenomic effects of estrogen, suggesting that GPR30 might be a G-protein coupled estrogen receptor. However, the findings are controversial and the expression pattern of GPR30 on a cell type level as well as its function in vivo remains unclear. Therefore, the objective of this study was to identify cell types that express Gpr30 in vivo by analyzing a mutant mouse model that harbors a lacZ reporter (Gpr30-lacZ) in the Gpr30 locus leading to a partial deletion of the Gpr30 coding sequence. Using this strategy, we identified the following cell types expressing Gpr30: 1) an endothelial cell subpopulation in small arterial vessels of multiple tissues, 2) smooth muscle cells and pericytes in the brain, 3) gastric chief cells in the stomach, 4) neuronal subpopulations in the cortex as well as the polymorph layer of the dentate gyrus, 5) cell populations in the intermediate and anterior lobe of the pituitary gland, and 6) in the medulla of the adrenal gland. In further experiments, we aimed to decipher the function of Gpr30 by analyzing the phenotype of Gpr30-lacZ mice. The body weight as well as fat mass was unchanged in Gpr30-lacZ mice, even if fed with a high-fat diet. Flow cytometric analysis revealed lower frequencies of T cells in both sexes of Gpr30-lacZ mice. Within the T-cell cluster, the amount of CD62L-expressing cells was clearly reduced, suggesting an impaired production of T cells in the thymus of Gpr30-lacZ mice.
AU  - Isensee, J.*
AU  - Meoli, L.*
AU  - Zazzu, V.*
AU  - Nabzdyk, C.*
AU  - Witt, H.*
AU  - Soewarto, D.*
AU  - Effertz, K.*
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Busch, D.*
AU  - Adler, T.
AU  - Hrabě de Angelis, M.
AU  - Irgang, M.*
AU  - Otto, C.*
AU  - Noppinger, P.R.*
C1  - 2084
C2  - 26214
SP  - 1722-1730
TI  - Expression pattern of G protein-coupled receptor 30 in LacZ reporter mice.
JO  - Endocrinology
VL  - 150
IS  - 4
PB  - Endocrine Soc
PY  - 2009
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Metabolomics is a powerful tool for identifying both known and new disease-related perturbations in metabolic pathways. In preclinical drug testing, it has a high potential for early identification of drug off-target effects. Recent advances in high-precision high-throughput mass spectrometry have brought the metabolomic field to a point where quantitative, targeted, metabolomic measurements with ready-to-use kits allow for the automated in-house screening for hundreds of different metabolites in large sets of biological samples. Today, the field of metabolomics is, arguably, at a point where transcriptomics was about 5 yr ago. This being so, the field has a strong need for adapted bioinformatics tools and methods. In this paper we describe a systematic analysis of a targeted quantitative characterization of more than 800 metabolites in blood plasma samples from healthy and diabetic mice under rosiglitazone treatment. We show that known and new metabolic phenotypes of diabetes and medication can be recovered in a statistically objective manner. We find that concentrations of methylglutaryl carnitine are oppositely impacted by rosiglitazone treatment of both healthy and diabetic mice. Analyzing ratios between metabolite concentrations dramatically reduces the noise in the data set, allowing for the discovery of new potential biomarkers of diabetes, such as the N-hydroxyacyloylsphingosyl-phosphocholines SM(OH)28:0 and SM(OH)26:0. Using a hierarchical clustering technique on partial eta(2) values, we identify functionally related groups of metabolites, indicating a diabetes-related shift from lysophosphatidylcholine to phosphatidylcholine levels. The bioinformatics data analysis approach introduced here can be readily generalized to other drug testing scenarios and other medical disorders.
AU  - Altmaier, E.
AU  - Ramsay, S.L.*
AU  - Graber, A.*
AU  - Mewes, H.-W.
AU  - Weinberger, K.M.*
AU  - Suhre, K.
C1  - 3638
C2  - 25532
SP  - 3478-3489
TI  - Bioinformatics analysis of targeted metabolomics - uncovering old and new tales of diabetic mice under medication.
JO  - Endocrinology
VL  - 149
IS  - 7
PB  - Endocrine Society
PY  - 2008
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - The EGF family comprises a network of ligands and receptors that regulate proper development and elicit diverse functions in physiology and pathology. Betacellulin (BTC) is a rather poorly characterized member of the EGF family whose in vivo effects have been linked mainly to endocrine pancreas, intestine, and mammary gland function. In vitro studies revealed that this growth factor is a potent mitogen for diverse cell types and suggested unique receptor-binding properties. Genetic ablation of BTC in mice yielded a mild phenotype, probably because of opportunistic compensation by other EGF receptor ligands. To study the biological capabilities of BTC in vivo, we generated transgenic mice overexpressing BTC ubiquitously, with highest expression levels in heart, lung, brain, and pancreas. Mice overexpressing BTC exhibit high early postnatal mortality, reduced body weight gain, and impaired longitudinal growth. In addition, a variety of pathological alterations were observed. Cataract and abnormally shaped retinal layers as well as bone alterations leading to a dome-shaped, round head form were hallmarks of BTC transgenic mice. The most important finding and the cause of reduced life expectancy of BTC transgenic mice were severe alterations of the lung. Pulmonary pathology was primarily characterized by alveolar hemorrhage, thickening of the alveolar septa, intraalveolar accumulation of hemosiderin-containing macrophages, and nodular pulmonary remodeling. Thus, our model uncovers multiple consequences of BTC overexpression in vivo. These transgenic mice provide a useful model for examining the effects of BTC excess on different organs.
AU  - Schneider, M.R.*
AU  - Dahlhoff, M.*
AU  - Herbach, N.*
AU  - Renner-Mueller, I.*
AU  - Dalke, C.
AU  - Puk, O.*
AU  - Graw, J.
AU  - Wanke, R.*
AU  - Wolf, E.*
C1  - 3705
C2  - 23220
SP  - 5237-5246
TI  - Betacellulin overexpression in transgenic mice causes disproportionate growth, pulmonary hemorrhage syndrome and complex eye pathology.
JO  - Endocrinology
VL  - 146
IS  - 12
PY  - 2005
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a-->g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice displaying a less pronounced phenotype. All genotypes are viable and fertile, and the mode of inheritance is in accordance with a semidominant Mendelian trait. Adult SMA1 mice accumulate excessive amounts of sc and visceral fat in the presence of elevated plasma ghrelin levels, possibly reflecting altered energy partitioning. Our results suggest impaired storage and/or secretion of pituitary GH in mutants, resulting in reduced pituitary GH and reduced GH-stimulated IGF-1 expression. Generation and identification of the SMA1 mouse exemplifies the power of the combination of random mouse mutagenesis with a highly detailed phenotype-analysis as a successful strategy for the detection and analysis of novel gene-function relationships.
AU  - Meyer, C.W.E.*
AU  - Korthaus, D.*
AU  - Jagla, W.*
AU  - Cornali, E.*
AU  - Grosse, J.*
AU  - Fuchs, H.
AU  - Klingenspor, M.*
AU  - Roemheld, S.*
AU  - Tschöp, M.H.*
AU  - Heldmaier, G.*
AU  - Hrabě de Angelis, M.
C1  - 5169
C2  - 22231
SP  - 2531-2541
TI  - A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia and obesity.
JO  - Endocrinology
VL  - 145
IS  - 5
PY  - 2004
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Recent investigations in mouse lines either deficient for the CRH receptor 1 (CRHR1) or 2 (CRHR2) suggest that the CRH neuronal system may comprise two separate pathways that can be coordinately and inversely activated in stress-induced hypothalamic-pituitary-adrenal (HPA) response and anxiety-like behavior. We generated mice deficient for both CRHR1 (Crhr1(-/-)) and CRHR2 (Crhr2(-/-)) to investigate the HPA system regulation in the absence of known functionally active CRH receptors under basal conditions and in response to different ethologically relevant stressors. To elucidate possible gene dose effects on the action of both CRH receptors, our analysis included heterozygous and homozygous CRHR1- or CRHR2-deficient mice, mutants lacking both CRH receptors, compound mutants with homozygous and heterozygous deficiency for either of the receptors, and their wild-type littermates. Both male and female Crhr1(-/-)Crhr2(-/-) mutants were viable, fertile, and indistinguishable in size from wild-type littermates. We show that the endocrine phenotype of mice lacking both CRHRs is dominated by the functional loss of CRHR1. CRHR2 does not compensate for CRHR1 deficiency, nor does the lack of CRHR2 exacerbate the CRHR1-dependent impairment of the HPA system function. Within the intraadrenal CRH/ACTH system, our data suggest different roles for CRHR1 and CRHR2 in fine-tuning of adrenocortical corticosterone release.
AU  - Preil, J.*
AU  - Müller, M.B.*
AU  - Gesing, A.*
AU  - Reul, J.M.H.M.
AU  - Sillaber, I.*
AU  - van Gaalen, M.M.*
AU  - Landgrebe, J.*
AU  - Holsboer, F.*
AU  - Stenzel-Poore, M.*
AU  - Wurst, W.
C1  - 843
C2  - 22823
SP  - 4946-4955
TI  - Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2.
JO  - Endocrinology
VL  - 142
IS  - 11
PY  - 2001
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - Deficiency of CRH receptor 1 (CRHR1) severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system and reduces anxiety-related behavior in mice. Intriguingly, in mice deficient for the CRHR1 (Crhr1-/-), basal plasma levels of ACTH are normal, suggesting the presence of compensatory mechanisms for pituitary ACTH secretion. We therefore studied the impact of the hypothalamic neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) on HPA system regulation in homozygous and heterozygous Crhr1 mutants under basal and different stress conditions. Basal plasma AVP concentrations were significantly elevated in Crhr1-/- mice. AVP messenger RNA expression was increased in the paraventricular nucleus of Crhr1-/- mutants together with a marked increase in AVP-like immunoreactivity in the median eminence. Administration of an AVP V1-receptor antagonist significantly decreased basal plasma ACTH levels in mutant mice. After continuous treatment with corticosterone, plasma AVP levels in homozygous Crhr1-/- mice were indistinguishable from those in wild-type littermates, thus providing evidence that glucocorticoid deficiency is the major driving force behind compensatory activation of the vasopressinergic system in Crhr1-/- mice. Neither plasma OXT levels under several different conditions nor OXT messenger RNA expression in the paraventricular nucleus were different between the genotypes. Taken together, our data reveal a selective compensatory activation of the hypothalamic vasopressinergic, but not the oxytocinergic system, to maintain basal ACTH secretion and HPA system activity in Crhr1-/- mutants.
AU  - Müller, M.B.*
AU  - Landgraf, R.*
AU  - Preil, J.*
AU  - Sillaber, I.*
AU  - Kresse, A.E.*
AU  - Keck, M.E.*
AU  - Zimmermann, S.*
AU  - Holsboer, F.*
AU  - Wurst, W.
C1  - 3803
C2  - 22818
SP  - 4262-4269
TI  - Selective activation of the hypothalamic vasopressinergic system in mice deficient for the corticotropin-releasing hormone receptor 1 is dependent on glucocorticoids.
JO  - Endocrinology
VL  - 141
IS  - 11
PY  - 2000
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - The 17β-hydroxysteroid dehydrogenase (17 βHSD) enzyme system governs important redox reactions at the C17 position of steroid hormones. Different 17 βHSD types (no. 1-4) have been identified to date in peripheral human tissues, such as placenta, testis, and breast. However, there is little information on their expression and activity in either normal or malignant prostate. In the present work, we have inspected pathways of 17 β-oxidation of either androgen or estrogen in human prostate cancer cells (LNCaP, DU145, and PC3) in relation to the expression of messenger RNAs (mRNAs) for 17 βHSD types 1-4. These cell systems feature distinct steroid receptor status and response to hormones. We report here that high expression levels of 17 βHSD4 were consistently observed in all three cell lines, whereas even greater amounts of 17 βHSD2 mRNA were detected solely in PC3 cells. Neither 17 βHSD1 nor 17 βHSD3 mRNAs could be detected in any cell line. From a metabolic standpoint, intact cell analysis showed a much lower extent of 17 β-oxidation of both androgen [testosterone (T)] and estrogen [estradiol (E2)] in LNCaP and DU145 cells compared to PC3 cells, where a greater precursor degradation and higher formation rates of oxidized derivatives (respectively, androstenedione and estrone) were observed. Using subcellular fractionation, we have been able to differentiate among 17 βHSD types 1-4 on the basis of their distinct substrate specificities and subcellular localization. This latter approach gave rise to equivalent results. PC3 cells, in fact, displayed a high level of microsomal activity with a low E2/T activity ratio and approximately equal apparent K(m) values for E2and T, suggesting the presence of 17 β3HSD2. Dehydrogenase specific activity with both E2and T was also detected, although at lower levels, in LNCaP and DU145 cells. No evidence for reductase activity could be obtained in either the soluble or microsomal fraction of any cell line. As comparable expression levels of 17 βHSD4 were seen in the three cell lines, 17 βHSD2 is a likely candidate to account for the predominant oxidative activity in PC3 cells, whereas 17 βHSD4 may account for the lower extent of E2oxidation seen in both LNCaP and DU145 cells. This is the first report on the expression of four different 17 βHSD types in human prostate cancer cells. It ought to be emphasized that for the first time, analysis of different 17 βHSD activities in either intact or fractionated cells harmonizes with the expression of relevant mRNAs species.
AU  - Castagnetta, L.A.M.*
AU  - Carruba, G.*
AU  - Traina, A.*
AU  - Granata, O.M.*
AU  - Markus, M.*
AU  - Pavone-Macaluso, M.*
AU  - Blomquist, C.H.*
AU  - Adamski, J.
C1  - 53847
C2  - 0
SP  - 4876-4882
TI  - Expression of different 17β-hydroxysteroid dehydrogenase types and their activities in human prostate cancer cells.
JO  - Endocrinology
VL  - 138
IS  - 11
PY  - 1997
SN  - 0013-7227
ER  - 

TY  - JOUR
AB  - In the present study we investigated pharmacological, biochemical, and immunological characteristics as well as the tissue distribution of the insulin-like growth factor-II/man nose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract, and compared the data with those from corresponding experiments for the IGF-I receptor. Competitive binding and affinity cross-linking studies with [125I]IGF-II, and [125I]IGF-I respectively, in rat jejunum yielded results analogous to those previously obtained for IGF-II/M6P and IGF-I receptors in intestinal epithelial membranes and other tissues. Furthermore, the IGF-II/M6P receptor antibody no. 3637 completely inhibited the association of [125I]IGF-II with receptor protein but nonimmune antibody did not, providing additional evidence for the presence of the IGF-II/M6P receptor in the rat gut. Also, analysis of the IGF-II/M6P receptor by immunoblotting using antiserum no. 3637 identified a specific band of mol wt 220.000 throughout the gastrointestinal tract with the highest content of immunoreactivity being present in colon and ileum.
AU  - Heinz-Erian, P.
AU  - Kessler, U.
AU  - Funk, B.
AU  - Gais, P.
AU  - Kiess, W.
C1  - 19474
C2  - 12569
SP  - 1769-1778
TI  - Identification and in Situ Localization of the Insulin-like Growth Factor-II/mannose-6-phosphate ( IGF-II/M6P) Receptor in the Rat Gastrointestinal Tract: Comparison with the IGF-I Receptor.
JO  - Endocrinology
VL  - 129
PY  - 1991
SN  - 0013-7227
ER  - 

TY  - JOUR
AU  - Kollmer, W.E.
AU  - Schramel, P.
AU  - Iyengar, G.V.
C1  - 41677
C2  - 35510
SP  - 115-120
TI  - Veränderungen der Konzentrationen von Na, Rb, Ca, Cu, Zn, Mo, Fe und Co in Blut und Uterus der Ratte während einer Östrogenbehandlung.
JO  - Endocrinology
VL  - 64
IS  - 1
PY  - 1974
SN  - 0013-7227
ER  -