Estrogen Exclusively Suppresses Kiss1 Expression in Arcuate Kndy Neurons in Prepubertal Female Rats

Presentation Number: SUN 480
Date of Presentation: April 2nd, 2017

Yoshihisa Uenoyama*1, Takuma Kobayashi1, Nahoko Ieda1, Naoko Inoue1, Kei-ichiro Maeda2 and Hiroko Tsukamura1
1Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan, 2Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan

Abstract

KNDy neurons expressing kisspeptin/neurokinin B/dynorphin A (which are encoded by Kiss1, Tac3 and Pdyn, respectively), localized in the hypothalamic arcuate nucleus (ARC), are considered a gatekeeper of puberty onset in mammals. The most plausible interpretation is that KNDy neurons act as a part of GnRH pulse generator, in which kisspeptin directly stimulates GnRH secretion, and neurokinin B and dynorphin A control GnRH pulses through modulation of the GnRH pulse generator activity. Our previous study demonstrated that estrogen plays a critical role in prepubertal suppression of ARC Kiss1 expression in female rats. For a deeper understanding of the brain mechanism underlying the pubertal increase in GnRH/gonadotropin secretion, the present study examined whether estrogen regulates ARC Tac3 and Pdyn expressions during the peripubertal period. Wistar-Imamichi female rats were ovariectomized (OVX) and some of them were subcutaneously implanted with a Silastic tubing containing estradiol (OVX+E) 6 days before the sacrifice. The OVX and OVX+E rats were perfused with a fixative and the hypothalami were collected at 26 (prepubertal period) and 41 (postpubertal period) days of age. Kiss1, Tac3 and Pdyn expressions were determined by in situ hybridization on serial coronal sections of the ARC. A large number of ARC Tac3- and Pdyn-expressing cells were constantly found in OVX and OVX+E rats in both the pre- and postpubertal periods. On the other hand, the number of ARC Kiss1-expressing cells was significantly lower in OVX+E rats than OVX controls in the prepubertal period, while a number of Kiss1-expressing cells were found in both OVX and OVX+E animals in the postpubertal period. The present results indicate that, among these three genes in KNDy neurones, Kiss1 expression is exclusively suppressed by prepubertal estrogen. Thus, the present study suggests that pubertal increase in ARC Kiss1 expression is primarily responsible for the timing of pubertal increase in GnRH/gonadotropin secretion in female rats.

 

Nothing to Disclose: YU, TK, NI, NI, KIM, HT