The ovary-mediated FSH attenuation of the LH surge in the rat involves a decreased gonadotroph progesterone receptor (PR) action but not PR expression

Abstract

Hyperstimulation of ovarian function with human FSH (hFSH) attenuates the preovulatory surge of LH. These experiments aimed at investigating the mechanism of ovarian-mediated FSH suppression of the progesterone (P 4 ) receptor (PR)-dependent LH surge in the rat. Four-day cycling rats were injected with hFSH, oestradiol benzoate (EB) or vehicle during the dioestrous phase. On pro-oestrus, their pituitaries were studied for PR mRNA and protein expression. Additionally, pro-oestrous pituitaries were incubated in the presence of oestradiol-17b (E 2 ), and primed with P 4 and LH-releasing hormone (LHRH), with or without the antiprogestin RU486. After 1 h of incubation, pituitaries were either challenged or not challenged 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 metoestrus (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 E 2 levels, gonadotroph PR-A/PR-B mRNA ratio or immunohistochemical protein expression; ii) incubated pro-oestrous pituitaries from hFSH-treated rats did not respond to P 4 or LHRH, and lacked E 2 -augmenting and LHRH self-priming effects and iii) OVX reversed the inhibitory effects of hFSH on LH secretion. It is concluded that under the influence of hFSH, the ovaries produce a non-steroidal factor which suppresses all PR-dependent events of the LH surge elicited by E 2 . The action of such a factor seemed to be due to a blockade of gonadotroph PR action rather than to an inhibition of PR expression.

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

“…The up-regulation of ERK1/2 signaling (Fan et al 2009) occurs coincident with the down-regulation of BMPR1B activity, which suppresses progesterone synthesis (Miyoshi et al 2006, Feary et al 2007. The failure to down-regulate BMPR1B activity would therefore impede the process of luteinization and prevent maturation of the follicle (Gordon et al 2008).…”

Attenuin: What It Is, How It Works and What It Does

“…The in vivo approach consists in administration of exogenous FSH during the diestrous phase in cycling rats as a tool to increase the biological activity of endogenous attenuin (Geiger et al, 1980;Gordon et al, 2008). In addition to attenuin, FSH also stimulates the synthesis and secretion by granulosa cells of a number of steroidal and non-steroidal factors (mainly estradiol and inhibin) that affect pituitary gonadotropin secretion (Arai et al, 1996;Watanabe et al, 1990).…”

“…In addition to attenuin, FSH also stimulates the synthesis and secretion by granulosa cells of a number of steroidal and non-steroidal factors (mainly estradiol and inhibin) that affect pituitary gonadotropin secretion (Arai et al, 1996;Watanabe et al, 1990). However, this treatment attenuates the magnitude of the proestrous afternoon LH surge despite the presence of high circulating levels of estradiol (Geiger et al, 1980;Gordon et al, 2008, de Koning et al, 1987see fig. 2A for additional details).…”

“…A number of published studies report a reduction of the preovulatory LH surge in vivo in rats treated with FSH during metestrus and diestrus (Culler, 1992;Geiger et al, 1980;Gordon et al, 2008;de Koning et al, 1987;Shuiling et al, 1999). Additionally, this FSH treatment in vivo causes an in vitro suppression of GnRH-stimulated LH secretion, GnRH self-priming and progesterone-potentiating effect on GnRH-stimulated LH secretion, without affecting basal LH levels (Byrne et al, 1996;Gordon et al, 2008;Koppenaal et al, 1992Koppenaal et al, , 1993.…”

“…Additionally, this FSH treatment in vivo causes an in vitro suppression of GnRH-stimulated LH secretion, GnRH self-priming and progesterone-potentiating effect on GnRH-stimulated LH secretion, without affecting basal LH levels (Byrne et al, 1996;Gordon et al, 2008;Koppenaal et al, 1992Koppenaal et al, , 1993. Pace Geiger et al (1980), the possibility that these effects are produced by an increase in estradiol levels can be ruled out, since animals treated with estradiol benzoate display greater LH secretion both in vivo and in vitro; more important, FSH plus estradiol-injected ovariectomized rats do not display any suppressant effect on LH secretion .…”