Estrogenic regulation of Kiss1 mRNA variants in Hatano rats

Differences in reproductive endocrinology distinguish Hatano high-avoidance animals (HAA) from low-avoidance animals (LAA). Compared to HAA rats, female LAA rats secrete low levels of basal luteinizing hormone (LH) and a reduced LH surge. To investigate the underlying cause of the differences between the two strains, levels of the following mRNAs were measured in the hypothalamus of intact and ovariectomized (OVX) females treated with vehicle control or estradiol-17β (E2): gonadotropin-releasing hormone (Gnrh), newly isolated rat kisspeptin (Kiss)1 mRNA variant-1 (Kiss1V1) and variant-2 (Kiss1V2) and estrogen receptor (Er) α. In OVX-HAA rats, the levels of Gnrh mRNA in the preoptic area (POA) 30 h after E2 treatment were significantly higher than in OVX-LAA rats. For HAA rats, the levels of Kiss1V1 and Kiss1V2 mRNA in the anteroventral periventricular nucleus (AVPV) were significantly higher in the E2-treated group than in the vehicle-treated group. In the arcuate nucleus (Arc) of HAA rats, Kiss1V1 and Kiss1V2 expression was significantly lower in E2-treated females compared to vehicle-treated females. Kiss1V2 expression was significantly higher than Kiss1V1 expression in intact HAA rats. In E2-treated OVX-LAA rats, there were no changes in the expression levels of Gnrh, Kiss1V1 or Kiss1V2. In intact LAA rats, no differences were observed in the expression levels of Kiss1V1 or Kiss1V2 in the AVPV, but the expression levels of these mRNAs in the Arc were significantly lower in E2-treated OVX-LAA rats. Additionally, no strain differences were observed for Erα mRNA expression in either the AVPV or Arc. These results indicate that the failure of estrogenic regulation of GnRH neurons in the POA and of kisspeptin neurons in the AVPV of LAA rats causes low LH secretion and reduced reproductive function.