Involvement of rat gonadotrope progesterone receptor in the ovary-mediated inhibitory action of FSH on LH synthesis (original) (raw)

Ovarian stimulation with FSH reduces phosphorylation of gonadotrope progesterone receptor and LH secretion in the rat

Reproduction, 2009

Administration of human FSH (hFSH) to cyclic rats during the dioestrous phase attenuates progesterone receptor (PR)-dependent events of the preovulatory LH surge in pro-oestrus. The increased bioactivity of the putative ovarian gonadotropin surge inhibiting/attenuating factor induced by hFSH treatment is not associated with a decrease in PR protein expression, and the possibility of its association at a PR posttranslational effect has been raised. The present experiments aimed to analyse PR phosphorylation status in the gonadotrope of rats with impaired LH secretion induced by in vivo hFSH injection. Two experimental approaches were used. First, incubated pro-oestrous pituitaries from hFSH-injected cycling and oestrogen-treated ovariectomized (OVX) rats were used to analyze the effect of calyculin, an inhibitor of intracellular phosphatases, on PR-dependent LH release, which was measured in the incubation medium by RIA. Second, pituitaries taken from hFSH-injected intact cycling and OVX rats and later incubated with P or GNRH1 were used to assess the phosphorylation rate of gonadotrope. The latter was analysed in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry using a MAB that recognizes the phosphorylated (p) form of PR at Ser294. Calyculin reduced the ovary-mediated inhibition of hFSH in GNRH1-stimulated LH secretion. In addition, the immunohistochemical expression of pSer294 PR was significantly reduced after ovarian stimulation with hFSH in pituitaries from pro-oestrous rats incubated with P or GNRH1. Altogether, these results suggested that the ovarian-dependent inhibitory effect of FSH injection on the preovulatory LH secretion in the rat may involve an increase in dephosphorylation of PR.

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

Journal of Endocrinology, 2007

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 (P4) 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-17β (E2), and primed with P4 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...

FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat

Human Reproduction, 1999

The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin ® ; 10 IU/injection) lowered the spontaneous pre-ovulatory LH-surge and suppressed the pituitary luteinizing hormone (LH) response to GnRH. FSH also suppressed the LH response of pseudopregnant (PSP) rats on day 8 of pseudopregnancy, but not that of day-8 PSP rats which had been ovariectomized on day 4 (OVX-PSP rats). GnRH induced self priming in cycling, PSP and OVX-PSP rats. Oestradiol strongly augmented the pituitary LH-response to GnRH injection in PSP and OVX-PSP rats, but not in cycling rats; probably because in these latter animals the LH response to GnRH was already augmented by endogenous oestradiol. FSH suppressed the LH response to GnRH in oestradiol-treated PSP and cycling rats; in these latter rats the suppression of the LH response was as strong as that in cycling rats not treated with oestradiol. FSH did not suppress the LH response of oestradiol-treated OVX-PSP rats. The effect of FSH was not associated with changes in plasma oestradiol and progesterone concentrations. Analysis of the data revealed that FSH specifically suppressed the augmentative effect of oestradiol, but did not affect the GnRH-self priming effect. It is concluded that under the influence of FSH, the ovaries produce a factor which suppresses the augmentative effect of oestradiol on the GnRH-induced LH response of the pituitary gland. It is suggested that this effect of FSH underlies the suppression of the spontaneous LHsurges of FSH-treated cycling rats. As the present putative 'oestrogen-antagonizing factor' did not suppress the GnRH-self priming effect, it is suggested that this factor is not identical to gonadotrophin surge inhibiting factor.

Facilitation or Inhibition of the Oestradiol-Induced Gonadotrophin Surge in the Immature Female Rat by Progesterone: Effects on Pituitary Responsiveness to Gonadotrophin-Releasing Hormone (GnRH), GnRH Self-Priming and Pituitary mRNAs for the Progesterone Receptor A and B Isoforms

Journal of Neuroendocrinology, 2007

Progesterone can either inhibit or facilitate the oestrogen-induced gonadotrophin surge during the rat oestrous cycle. If progesterone is administered to female rats during the early part of the cycle before oestrogen priming, it will prevent or truncate the pro-oestrous preovulatory surge of luteinising hormone (LH) (1-3). A similar blockade of the LH surge by progestins occurs in women (4), monkeys (5) and ewes (6), providing the basis for the development of oral contraceptive drugs. Progesterone also inhibits LH release in the oestrogen-treated immature female rat (7, 8) and in the ovariectomised (OVX) adult rat, either when administered in conjunction with oestradiol (E 2) (9), or at selected times following oestrogen priming (10, 11). Facilitation of LH discharges by progesterone, on the other hand, can be demonstrated only after a period of oestrogen priming. This facilitatory effect is manifested in the 5-day cyclic rat by a 24 h advance in ovulation (1) and in the 4-day cyclic rat (2, 12) or oestrogen-primed OVX (10) or immature (7, 8) rat by gonadotrophin release within 5 h of progesterone treatment. The abrupt

Inhibition of LHRH-induced LH and FSH release by gonadotrophin surge-attenuating factor (GnSAF) from human follicular fluid

Reproduction, 1990

It has been suggested that in superovulated women the endogenous LH surge is attenuated by a non-steroidal factor, called gonadotrophin surge-attenuating factor (GnSAF), which reduces gonadotrophin secretion in response to LHRH. To determine whether human follicular fluid (hFF) from superovulated women contains GnSAF activity, the secretion of LH and FSH by cultured sheep pituitaries was studied. After charcoal extraction of steroids, hFF was treated by heparin/Sepharose chromatography, which reversibly binds inhibin. The effects of whole hFF and the bound and unbound fractions on basal and LHRH-induced gonadotrophin secretion were then assessed. Steroid-free hFF significantly reduced basal FSH, but not basal LH, secretion, and significantly attenuated the LH and FSH responses to LHRH. The bound (inhibin) fraction significantly decreased both basal and LHRH-induced FSH secretion but did not affect LH release. The unbound fraction had no effect on basal LH or FSH secretion, but significantly attenuated LHRH-induced secretion of both LH and FSH. We conclude that the unbound fraction of hFF from superovulated women contains GnSAF. It has been demonstrated that GnSAF is a non-steroidal factor and its activity is distinct from that of inhibin.

Inhibition of LHRH-induced LH and FSH release bym gonadotrophin surge-attenuating factor (GnSAF) from human follicular fluid

Journal of Reproduction and Fertility, 1990

It has been suggested that in superovulated women the endogenous LH surge is attenuated by a non-steroidal factor, called gonadotrophin surge-attenuating factor (GnSAF), which reduces gonadotrophin secretion in response to LHRH. To determine whether human follicular fluid (hFF) from superovulated women contains GnSAF activity, the secretion of LH and FSH by cultured sheep pituitaries was studied. After charcoal extraction of steroids, hFF was treated by heparin/Sepharose chromatography, which reversibly binds inhibin. The effects of whole hFF and the bound and unbound fractions on basal and LHRH-induced gonadotrophin secretion were then assessed. Steroid-free hFF significantly reduced basal FSH, but not basal LH, secretion, and significantly attenuated the LH and FSH responses to LHRH. The bound (inhibin) fraction significantly decreased both basal and LHRH-induced FSH secretion but did not affect LH release. The unbound fraction had no effect on basal LH or FSH secretion, but significantly attenuated LHRH-induced secretion of both LH and FSH. We conclude that the unbound fraction of hFF from superovulated women contains GnSAF. It has been demonstrated that GnSAF is a non-steroidal factor and its activity is distinct from that of inhibin.

Follicle stimulating hormone stimulates the production of gonadotrophin surge attenuating factor (GnSAF) in vivo

Clinical Endocrinology, 1991

follicle-stimulating hormone and human menopausal gonadotropin in normal women and polycystic ovary syndrome. Fertility and Sterility, 52,2 16220. Busbridge, N.J., Chamberlain, G.V.P., Griffiths, A. & Whitehead, S.A. (1990) Non-steroidal follicular factors attenuate the selfpriming action of gonadotropin-releasing hormone on the pituitary gonadotroph. Neuroendocrinology, 51,493-499. Fowler, P.A., Messinis, LE. & Templeton, A.A. (199Oa) Inhibition of LHRH-induced LH and FSH release by gonadotrophin surgeattenuating factor (GnSAF) from human follicular fluid. Journal of Reproduction and Ferlility, 90,587-594. Fowler, P.A., Messinis, I.E. & Templeton, A.A. (l99Ob) Gonadotrophin surge-attenuating factor (GnSAF) is produced preferentially by small follicles in superovulated women. Journal of Reproduction and Fertility, Abstract Series No. 5, 8. Keye, W.R. & Jaffe, R.B. (1974) Modulation ofpituitary gonadotropin response to gonadotropin-releasing hormone by estradiol. Demonstration of a nonsteroidal factor in human follicular fluid that attenuates the self-priming action of gonadotrophin-releasing hormone on pituitary gonadotropes. Biology of Reproduction, 42,613-618.