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Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice

Authors
Journal
Molecular and Cellular Endocrinology
0303-7207
Publisher
Elsevier
Publication Date
Volume
332
Identifiers
DOI: 10.1016/j.mce.2010.09.016
Keywords
  • Hypothalamic–Pituitary-Axis
  • Androgen
  • Human Chorionic Gonadotrophin
  • Follicle Stimulating Hormone
  • Transgenic Model
Disciplines
  • Computer Science

Abstract

Abstract Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic–pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic–pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.

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