Ancel Caroline, Inglis Megan A, Anderson Greg M
Centre for Neuroendocrinology and Department of Anatomy, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
Endocrinology. 2017 Sep 1;158(9):2873-2883. doi: 10.1210/en.2016-1902.
RFamide-related peptide (RFRP)-3 is a neuropeptide thought to play an inhibitory role in the regulation of reproduction in various mammalian species, although some stimulatory effects have been reported. To date, the effects of RFRP-3 on gonadotropin secretion have been scarcely studied in mice. The aim of the current study was to characterize the effect of RFRP-3 administration on gonadotropin secretion in male and female mice. Adult intact and castrated male mice received acute central injections of 0.5 to 5 nmol of RFRP-3, and luteinizing hormone (LH) concentration was assayed in tail-tip blood samples. RFRP-3 had a dose-dependent stimulatory effect on LH secretion when administered centrally to both intact and castrated mice, and this effect was diminished when RFRP-3 was administered to kisspeptin receptor knockout mice. In female mice, central RFRP-3 had an inhibitory effect on LH secretion when administered at the time of the preovulatory LH surge in intact mice, or of an estradiol-induced LH surge in ovariectomized mice. Conversely, central RFRP-3 administration had no effect on LH levels in intact diestrus or ovariectomized, low-dose estradiol-implanted mice. Finally, peripheral administration of RFRP-3 to intact males and to females at the time of the preovulatory LH surge or during diestrus had no effect on LH secretion. Taken together, these results provide a detailed description of sex- and cycle stage-dependent effects of RFRP-3 on gonadotrophin secretion in mice. Moreover, it appears that the stimulatory effects are mediated in part by the receptor for kisspeptin, a potent stimulator of the reproductive axis.
促性腺激素释放激素相关肽（RFRP）-3是一种神经肽，尽管有报道称其有一些刺激作用，但一般认为它在多种哺乳动物的生殖调节中起抑制作用。迄今为止，RFRP-3对小鼠促性腺激素分泌的影响鲜有研究。本研究的目的是明确RFRP-3给药对雄性和雌性小鼠促性腺激素分泌的影响。成年未阉割和阉割的雄性小鼠接受0.5至5纳摩尔RFRP-3的急性中枢注射，并检测尾尖血样中的黄体生成素（LH）浓度。向未阉割和阉割的小鼠中枢给药时，RFRP-3对LH分泌有剂量依赖性刺激作用，而向亲吻素受体基因敲除小鼠给药时，这种作用减弱。在雌性小鼠中，在未阉割小鼠排卵前LH峰出现时或去卵巢小鼠雌二醇诱导的LH峰出现时，中枢给予RFRP-3对LH分泌有抑制作用。相反，在未阉割的间情期或去卵巢、低剂量雌二醇植入的小鼠中，中枢给予RFRP-3对LH水平没有影响。最后，在排卵前LH峰出现时或间情期，向未阉割的雄性和雌性小鼠外周给予RFRP-3对LH分泌没有影响。综上所述，这些结果详细描述了RFRP-3对小鼠促性腺激素分泌的性别和周期阶段依赖性影响。此外，刺激作用似乎部分由亲吻素受体介导，亲吻素是生殖轴的一种有效刺激物。
