Molecular and cellular endocrinology
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Our understanding of Polycystic Ovary Syndrome (PCOS) has been hampered by varying diagnostic criteria, and ignorance of the etiology of the syndrome. PCOS women are uniquely insulin resistant and obesity aggravates this underlying predisposition to insulin resistance. ⋯ Improving insulin sensitivity has become established as a baseline treatment strategy in PCOS. There are, however, few randomized controlled trials of adequate power to provide an evidence based guide to treatment in PCOS.
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Androgens are important steroid hormones for expression of the male phenotype. They have characteristic roles during male sexual differentiation, during development and maintenance of secondary male characteristics, and during the initiation and maintenance of spermatogenesis. The two most important androgens in this respect are testosterone and 5 alpha-dihydrotestosterone. ⋯ However, in cases of CAIS no phenotypic variation has been described within one single family, in contrast to families with individuals with PAIS. In general AIS, can be routinely analyzed and more than 150 different mutations have been reported now. Differential diagnosis of AIS is possible with syndromes presenting with almost similar phenotypes but with a completely different molecular cause.
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The ethos of cancer treatment now lies in 'quality survival'. Fertility potential and preservation for male and female cancer patients has become an important feature of their management. We explore some issues about cancer, its treatment and how it could manifest itself in the fertility and reproductive health of these patients.
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Mol. Cell. Endocrinol. · Dec 1999
SOCS-1, -2, -3: selective targets and functions downstream of the prolactin receptor.
Suppressors of cytokine signaling, SOCS-1, SOCS-2 and SOCS-3, are non-transmembrane proteins with Src-homology-2 (SH2) domain, involved in negative regulation of the Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway. Using transient overexpression system the role of SOCS proteins in regulating prolactin receptor intracellular mediators leading to gene activation was analyzed. Overexpression of SOCS-1 led to a significant reduction in PRLR-mediated tyrosyl phosphorylation of Jak2, PRLR, Stat5 and the cytoplasmic protein tyrosine phosphatase SHP2. ⋯ Finally, the role of SOCS proteins in regulating the biological activity of the PRLR was investigated. Unlike SOCS-2, both SOCS-1 and SOCS-3 abolished the ability of the PRLR to induce beta-casein gene promoter activation. These results demonstrate that SOCS-1, SOCS-2 and SOCS-3 are differentially implicated in PRLR signaling to gene activation.
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Mol. Cell. Endocrinol. · Jun 1999
Modulation of androgen receptor (AR)-mediated transcriptional activity by EGF in the developing mouse reproductive tract primary cells.
Recently, a role for epidermal growth factor in male sexual differentiation was reported from different laboratories. We demonstrated that androgen receptor (AR) mediates the EGF-induced effects. The mechanism, by which EGF modulates AR mediated activity, is not known and the current studies were designed to investigate the role of AR. ⋯ Flutamide, an AR antagonist, also blocked the enhancement of luciferase activity induced by EGF and testosterone, further confirming the role of AR in the effect of EGF and testosterone. Thus, it appears that EGF-modulation of sexual differentiation involves enhancement of AR-mediated transcriptional activity and not enhancement of AR gene expression. Additionally, it appears that EGF modulates sexual differentiation in the presence of testosterone possibly by potentiating the testosterone-effect.