The oestrus cycle of the ewe is characterised by a long luteal phase follow
ed by a short follicular phase and these periods are related to the product
ion by the ovary of two major steroids: progesterone and oestrogen. Progest
erone 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 insig
hts into this mechanism. While progesterone removal induces a rapid increas
e in GnRH pulse frequency, progesterone reinsertion inhibits GnRH release e
ven faster: less than 50 minutes. This action of progesterone is specific t
o the gonadotrophic axis and is mediated through an action on the nuclear r
eceptor. Interestingly, this rapid mechanism is also strongly dependant of
prior exposure to both progesterone and oestradiol. During the follicular p
hase, the rise in circulating oestradiol induces a robust preovulatory GnRH
surge. In the ewe, this positive feedback effect is mainly exerted by an a
ction of oestradiol on the mediobasal hypothalamus. Finally, we have also o
btained evidence that progesterone priming is important for the full expres
sion of the positive feedback action of oestradiol on GnRH secretion. In su
mmary, progesterone and oestradiol sequentially exert opposite feedback eff
ects on GnRH secretion during the oestrus cycle of the ewe but there is als
o clear evidence that the systems affected by these steroids are intimately
linked.