Hypothalamic effects of progesterone on regulation of the pulsatile and surge release of luteinising hormone in female rats

Wen He,Xiaofeng Li,Kevin T O’Byrne,Hui Long,Daniel Adekunbi,Yanping Kuang,Yali Liu,Qifeng Lyu,Li Wang

doi:10.1038/s41598-017-08805-1

Abstract

Progesterone can block the oestradiol-induced GnRH/LH surge and inhibit LH pulse frequency. Recent studies reported that progesterone prevented premature LH surges during ovarian hyperstimulation in women. As the most potent stimulator of GnRH/LH release, kisspeptin is believed to mediate the positive and negative feedback effects of oestradiol in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, while the region-specific role of progesterone receptors in these nuclei remains unknown. This study examined the hypothesis that progesterone inhibits LH surge and pulsatile secretion via its receptor in the ARC and/or AVPV nuclei. Adult female rats received a single injection of pregnant mare serum gonadotropin followed by progesterone or vehicle. Progesterone administration resulted in a significant prolongation of the oestrous cycle and blockade of LH surge. However, microinjection of the progesterone receptor antagonist, RU486, into the AVPV reversed the prolonged cycle length and rescued the progesterone blockade LH surge, while RU486 into the ARC shortened LH pulse interval in the progesterone treated rats. These results demonstrated that progesterone’s inhibitory effect on the GnRH/LH surge and pulsatile secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respectively, which are essential for progesterone regulation of oestrous cyclicity in rats.

Highlights

Progesterone can block the oestradiol-induced gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge and inhibit LH pulse frequency
Microinjection of the progesterone receptor antagonist, RU486, into the anteroventral periventricular (AVPV) reversed the prolonged cycle length and rescued the progesterone blockade LH surge, while RU486 into the ARC shortened LH pulse interval in the progesterone treated rats. These results demonstrated that progesterone’s inhibitory effect on the GnRH/LH surge and pulsatile secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respectively, which are essential for progesterone regulation of oestrous cyclicity in rats
Ablation of KNDy neurones robustly increased the magnitude of the E2-induced LH surge in ovariectomised rats[24], which may be mediated by their projections to the AVPV kisspeptin neurones[25] or directly to the GnRH neuronal cell bodies in the medial preoptic area[26] and/or terminals in the median eminence[25]

Summary

Introduction

Progesterone can block the oestradiol-induced GnRH/LH surge and inhibit LH pulse frequency. As the most potent stimulator of GnRH/LH release, kisspeptin is believed to mediate the positive and negative feedback effects of oestradiol in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, while the region-specific role of progesterone receptors in these nuclei remains unknown. Microinjection of the progesterone receptor antagonist, RU486, into the AVPV reversed the prolonged cycle length and rescued the progesterone blockade LH surge, while RU486 into the ARC shortened LH pulse interval in the progesterone treated rats These results demonstrated that progesterone’s inhibitory effect on the GnRH/LH surge and pulsatile secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respectively, which are essential for progesterone regulation of oestrous cyclicity in rats. Given the afore-mentioned, the role of AVPV and ARC PR in progesterone negative feedback effect on pulsatile LH secretion as well as the LH surge in the rodent remains unclear

Methods

Results

Conclusion