Conditional knockout of the androgen receptor in gonadotropes reveals crucial roles for androgen in gonadotropin synthesis and surge in female mice.
Conditional knockout of the androgen receptor in gonadotropes reveals crucial roles for androgen in gonadotropin synthesis and surge in female mice.
复制标题
DOI：
10.1210/me.2014-1154
复制
发表时间：
2014-08
影响因子：
--
通讯作者：
Sheng Wu;Yi Chen;Temi Fajobi;S. DiVall;Chawnshang Chang;S. Yeh;A. Wolfe
中科院分区：
文献类型：
--
作者：
Sheng Wu;Yi Chen;Temi Fajobi;S. DiVall;Chawnshang Chang;S. Yeh;A. Wolfe
多囊卵巢综合征是导致育龄妇女不孕的主要原因。多囊卵巢综合征与高循环雄激素水平和代谢功能受损有关。本研究的目的是了解雄激素信号如何通过雄激素受体（AR）影响生殖功能。我们敲除垂体促性腺激素细胞（PitARKO）中的AR基因，以探讨雄激素对雌性小鼠生殖功能发育的作用。对照组和PitARKO同窝仔的青春期年龄无差异，通过阴道张开和首次发情的年龄进行评估。还研究了周期性和生育力，对照和PitARKO小鼠之间没有显著差异。我们观察到基础FSH血清和mRNA水平显著降低，而LH血清和mRNA水平无相应变化。尽管对照组和PitARKO组雌性小鼠的窝仔数相同，但PitARKO组小鼠的窝仔数显著较小。PitARKO雌性动物对卵巢切除术的LH和FSH反应随着LH/FSH激素和mRNA水平的降低而改变。这种减少可能是由于激活素A/B和gnrhr的表达减少。PitARKO小鼠排卵前LH和FSH峰水平显著降低。对照组和PitARKO小鼠的黄体数量减少，而窦状卵泡数量相似。总的来说，垂体AR通过调节LH/FSH的表达和分泌，有助于LH峰的形成和正常的生殖功能。
Polycystic ovary syndrome is the major cause of infertility in reproductive aged women. Polycystic ovary syndrome is associated with high circulating levels of androgens and impaired metabolic function. The goal of this study was to understand how androgen signaling via the androgen receptor (AR) affects reproductive function. We knocked out the AR gene specifically in pituitary gonadotropes (PitARKO) to explore the role of androgen on the development of reproductive function in female mice. There was no difference in the age of puberty between control and PitARKO littermates, which was assessed by the ages of vaginal opening and first estrus. Cyclicity and fertility were also studied, and there was no significant difference between control and PitARKO mice. We observed a significant decrease in basal FSH serum and mRNA levels with no corresponding change in LH serum and mRNA levels. Although the numbers of litters born to control and PitARKO females were the same, the litter size was significantly smaller for PitARKO mice. The LH and FSH responses to ovariectomy was altered with reduced LH/FSH hormone and mRNA levels in PitARKO females. This reduction may be due to reduced expression of activin A/B and gnrhr. The preovulatory surge levels of LH and FSH were dramatically lower in PitARKO mice. The number of corpora lutea was decreased whereas the number of antral follicles was similar between control and PitARKO mice. Overall the pituitary AR contributes to the elaboration of the LH surge and normal reproductive function by regulating LH/FSH expression and secretion.