Polycystic ovary syndrome (PCOS) is a female endocrine disorder and is characterized
by anovulation, menstrual irregularity and condition of androgen excess.
Kisspeptin is implicated in ovulation and follicular development by stimulation
of GnRH/luteinizing hormone (LH) secretion. The purpose of this study was to
determine whether chronic exposure to androgen affects expression of kisspeptin
and LH release in female rats, because women with PCOS show hyperandrogenism.
Weaned female rats were implanted subcutaneously with 90-days
continuous-release pellets of 5a-dihydrotestosterone
(DHT), and were used after 10 wk of age. Kiss1
mRNA-expressing cells in both the anteroventral periventricular nucleus (AVPV)
and arcuate nucleus (ARC) were significantly decreased in DHT-implanted group. AVPV
kisspeptin neurons are known to be involved in LH surge generation and are
positively regulated by estrogen. DHT animals could not detect estradiol
(E2)-induced LH surge, while there were no significant differences in numbers
of AVPV Kiss1 cells, kisspeptin-immunoreactive
(ir) cells and GnRH-ir cells between both groups in the presence of high E2. ARC
kisspeptin neurons are considered to participate in pulsatile LH release and
are a target of estrogen-negative feedback action. ARC Kiss1 cells were significantly decreased in ovariectomized (OVX)
DHT rats compared to OVX rats. Pulsatile LH secretion was suppressed in OVX DHT
rats. Central injection of kisspeptin-10 or intravenous injection of GnRH
agonist did not affect LH release in DHT animals. These results suggest that
hyperandrogenism may suppress LH surge and pulsatile LH secretion through
decreasing responsiveness to GnRH in the pituitary and inhibition of ARC
kisspeptin expression. On the other hand, AVPV kisspeptin neurons may be
unaffected by androgen. Hence, hyperandrogenism in PCOS may be associated with
anovulation and menstrual irregularity by adversely affecting ARC kisspeptin
neurons and the pituitary.