Gonadotrope androgen receptor mediates pituitary responsiveness to hormones and androgen-induced subfertility

JCI Insight
Zhiqiang WangSheng Wu

Abstract

Many women with hyperandrogenemia suffer from irregular menses and infertility. However, it is unknown whether androgens directly affect reproduction. Since animal models of hyperandrogenemia-induced infertility are associated with obesity, which may impact reproductive function, we have created a lean mouse model of elevated androgen using implantation of low dose dihydrotestosterone (DHT) pellets to separate the effects of elevated androgen from obesity. The hypothalamic-pituitary-gonadal axis controls reproduction. While we have demonstrated that androgen impairs ovarian function, androgen could also disrupt neuroendocrine function at the level of brain and/or pituitary to cause infertility. To understand how elevated androgens might act on pituitary gonadotropes to influence reproductive function, female mice with disruption of the androgen receptor (Ar) gene specifically in pituitary gonadotropes (PitARKO) were produced. DHT treated control mice with intact pituitary Ar (Con-DHT) exhibit disrupted estrous cyclicity and fertility with reduced pituitary responsiveness to GnRH at the level of both calcium signaling and LH secretion. These effects were ameliorated in DHT treated PitARKO mice. Calcium signaling controls GnRH re...Continue Reading

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Citations

Apr 21, 2020·Endocrine Reviews·Elisabet Stener-VictorinDavid H Abbott

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Methods Mentioned

BETA
immunoprecipitation
ChIP
ELISA
Assay
PCR

Software Mentioned

GraphPad Prism
GraphPad

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