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Abstract
<p class="first" id="d86696e120">Hypersecretion of luteinizing hormone (LH) is a common
endocrinological finding of
polycystic ovary syndrome (PCOS). This derangement might have a close relationship
with hypothalamic kisspeptin expression that is thought to be a key regulator of gonadotropin-releasing
hormone (GnRH). We evaluated the relationship between the hypothalamic-pituitary-gonadal
axis (HPG axis) and kisspeptin using a rat model of PCOS induced by letrozole. Letrozole
pellets (0.4 mg/day) and control pellets were placed subcutaneously onto the backs
of 3-week-old female Wistar rats. Body weight, vaginal opening and vaginal smear were
checked daily. Blood and tissues of ovary, uterus and brain were collected at 12-weeks
of age. An hypothalamic block was cut into anterior and posterior blocks, which included
the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), respectively,
in order to estimate hypothalamic kisspeptin expression in each area. The letrozole
group showed a similar phenotype to human PCOS such as heavier body weight, heavier
ovary, persistent anovulatory state, multiple enlarged follicles with no corpus luteum
and higher LH and testosterone (T) levels compared to the control group. Kisspeptin
mRNA expression in the posterior hypothalamic block including ARC was higher in the
letrozole group than in the control group although its expression in the anterior
hypothalamic block was similar between groups. These results suggest that enhanced
KNDy neuron activity in ARC contributes to hypersecretion of LH in PCOS and might
be a therapeutic target to rescue ovulatory disorder of PCOS in the future.
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