In female rats, long‑term exposure to the male hormone DHT cuts down the number of kisspeptin‑producing cells in a brain area that drives regular hormone pulses, which in turn blunts the natural LH surge needed for ovulation. Even giving extra kisspeptin‑10 or a GnRH drug didn’t revive LH release, showing that high androgen levels can block the whole pathway. This hints that in people with high androgen conditions (like PCOS), kisspeptin‑based tricks may not work unless the excess androgen is first reduced.

Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5&#x3b1;-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of <i>Kiss1</i>-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV <i>Kiss1</i>-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. <i>Kiss1</i>-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC <i>Kiss1</i>-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few <i>Kiss1</i>-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities.