Dynamics of steroid regulation of GnRH secretion during the oestrus cycle of the ewe.

The oestrus cycle of the ewe is characterised by a long luteal phase followed by a short follicular phase and these periods are related to the production by the ovary of two major steroids: progesterone and oestrogen. Progesterone exerts a strong inhibitory effect on GnRH secretion during the luteal phase by a mechanism which is still unknown. Using an oestrogen-free ovine model and the portal blood collection technique we have obtained new insights into this mechanism. While progesterone removal induces a rapid increase in GnRH pulse frequency, progesterone reinsertion inhibits GnRH release even faster: less than 50 minutes. This action of progesterone is specific to the gonadotrophic axis and is mediated through an action on the nuclear receptor. Interestingly, this rapid mechanism is also strongly dependent of prior exposure to both progesterone and oestradiol. During the follicular phase, the rise in circulating oestradiol induces a robust preovulatory GnRH surge. In the ewe, this positive feedback effect is mainly exerted by an action of oestradiol on the mediobasal hypothalamus. Finally, we have also obtained evidence that progesterone priming is important for the full expression of the positive feedback action of oestradiol on GnRH secretion. In summary, progesterone and oestradiol sequentially exert opposite feedback effects on GnRH secretion during the oestrus cycle of the ewe but there is also clear evidence that the systems affected by these steroids are intimately linked.