Mechanisum Of Progesterone On Regulation Of The Pulsatile And Surge Release Of Luteinising Hormone In Female Rats

Objective:Premature LH surges are a maj or cause for cycle cancellation during controlled ovarian stimulation(COH)in women undergoing in vitro fertilization(IVF).Efforts to minimize the occurrence of a premature LH surge have mainly relied on the use of GnRH agonist and antagonist,which exert increased procedural complexity and greater risk of side effects.A number of studies have shown that progesterone acts as an effective alternative for the prevention of the premature LH surge in COH.Early studies indicate the hypothalamus mediates the feedback effect of progesterone to suppress LH surges.However,the underlying mechanisms remain to be established.This study was designed to test the hypothesis that progesterone may prevent premature LH surges via progesterone receptor mediated mechanisms in the hypothalamic arcuate(ARC)and/or anteroventral periventricular(AVPV)nuclei;loci known to be involved in LH pulse and LH surge generation.Methods:Adult female Sprague-Dawley rats were given either a single injection of pregnant mare serum gonadotropin(PMSG,150IU/kg,i.p.)to induce follicle development or a single injection of PMSG followed by progesterone(5mg/kg,i.p.bid)for two days.Using bilateral microinjections of the anti-progestin RU486(5ng/μl,0.8 μl,dissolved in 20%DMSO and 20%ethylene glycol)into the ARC or AVPV immediately before each progesterone inj ection,we investigated the influence of progesterone or RU486 on estrous cyclicity and the LH surge.Results:Our results indicated that progesterone prevents premature LH surges during superovulation in rats.The prolonged estrous cycle,particularly its metestrus stage is mediated by progesterone receptors in AVPV and ARC.These results suggest that both the hypothalamic AVPV and ARC nuclei may be essential for progesterone regulation of LH surges and estrous cyclicity in the ratConclusions:These results demonstrated that progesterone prevents premature LH surges during superovulation in rats.Progesterone effects within the region of hypothalamic AVPV nuclei to block premature LH in PMSG-primed rats,while inhibit the LH pulsatile secretion via its receptor in the ARC.Moreover,the prolongation of oestrous cycle after administration of luteal-phase level of progesterone is mediated by its receptors in AVPV These results are consistent with the hypothesis that progesterone inhibitory effect on the GnRH and LH surge and pulsatile secretion mediated by its receptor in the hypothalamic AVPV and ARC respectively,which and are essential for progesterone regulation of oestrous cyclicity in rats.