Hyperstimulation of ovarian function with FSH attenuates the preovulatory surge of LH. The present experiments aimed at investigating the mechanism of the ovarian-mediated FSH suppression of progesterone (P4) receptor (PR)-dependent LH surge in the rat: estradiol (E2)-augmenting GnRH-induced LH secretion and E2-dependent GnRH self-priming effects. Four-day cycling rats were injected with hFSH, estradiol benzoate (EB) or oil during diestrous phase. On proestrus their pituitaries were studied for PR mRNA and protein expression. Moreover, proestrous pituitaries were incubated in the presence of E2, and primed with P4 and LHRH, with or without the antiprogestin RU486. After 1-hour incubation, pituitaries were challenged or not with LHRH. Measured basal and LHRH-stimulated LH secretions and LHRH self-priming were compared with those exhibited by incubated pituitaries on day 4 from ovariectomized (OVX) rats in metestrus (day 2) injected with hFSH and/or EB on days 2 and 3. The results showed that: i) hFSH lowered the spontaneous LH surge without affecting basal LH and E2 levels, gonadotrope PR mRNA and immunohistochemical protein expression; ii) incubated proestrous pituitaries from hFSH-treated rats did not respond to P4 or LHRH and lacked E2-augmenting and LHRH self-priming effects; and iii) OVX reversed the inhibitory effects of injected hFSH on LH secretion. It is concluded that under the influence of hFSH, the ovaries produce a factor which suppresses all PR-dependent events of the LH surge elicited by E2. The action of such a factor, either estrogen-antagonizing and/or gonadotropin-surge inhibiting/attenuating, seemed to be at gonadotrope PR action rather than at PR expression.