Gonadotropin Surge-Attenuating Factor Bioactivity in Serum from Superovulated Women is not Blocked by Inhibin Antibody1

Byrne, Bridgette; Fowler, Paul A.; Fraser, Margaret; Culler, Michael D.; Templeton, Allan

doi:10.1095/biolreprod52.1.88

Cited by 21 publications

(20 citation statements)

References 23 publications

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“…Several authors report that inhibin could be the FSH-dependent GnSAF [36,43,44]. The present results, however, agree with others [3,5,6,8,42,45,46,47] indicating that, regardless of whether inhibin might have some GnSAF activity [43], an ovarian factor other than inhibin is involved in the reduction in LH levels on the proestrous afternoon [1,2]. This is because after an intravenous injection of 400 µl AIS at 11:00 h in metestrus, free AIS levels remained high throughout the cycle until the morning of estrus [22], and the serum levels of FSH were elevated after the injection of AIS, at least until the proestrous afternoon.…”

Section: Discussionsupporting

confidence: 91%

Immunoneutralization of Inhibin in Cycling Rats Increases Follicle-Stimulating Hormone Secretion, Stimulates the Ovary and Attenuates Progesterone Receptor-Dependent Preovulatory Luteinizing Hormone Secretion

Gordon

Aguilar²,

Garrido‐Gracia³

et al. 2010

Neuroendocrinology

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Passive immunization against inhibin with an anti-inhibin serum (AIS) during the diestrous phase in cycling rats increased follicle-stimulating hormone secretion, stimulated the ovaries and reduced the magnitude of the luteinizing hormone (LH) surge in the afternoon of proestrus. The involvement of gonadotrope progesterone receptor (PR) expression/action in the inhibitory effects of the follicle-stimulating hormone-dependent putative ovarian factor gonadotropin surge-attenuating factor on preovulatory LH secretion was studied in the absence of circulating free inhibin. Proestrous pituitaries from rats injected with AIS or a non-immune serum (NIS) were studied for determination of PR-AB and PR-B mRNAs by RT-PCR and PR-B and PR-A isoform proteins by Western blot. In addition, pituitaries from AIS- and NIS-injected rats were incubated and studied for PR-dependent LH secretion parameters: LH-releasing hormone (LHRH)-stimulated LH secretion, progesterone-potentiated LHRH-stimulated LH secretion and LHRH self-priming. Also, the effects of the antiprogestagen RU486 on these LH secretion parameters were evaluated and compared with those of AIS. Finally, gonadotrope PR phosphorylation was evaluated by immunohistochemistry. Results showed that the hyperstimulated ovaries of AIS-injected rats produce a factor, different from inhibin, that blocked LHRH self-priming and P-potentiation of LHRH-stimulated LH secretion. These effects were not due to decreased pituitary PR mRNAs, PR protein expression or PR protein B/A ratio. The inhibitory effect of AIS on PR-dependent LH secretion seemed to be due to gonadotrope PR dephosphorylation. Taken together, the findings indicated that the putative gonadotropin surge-attenuating factor affected LH surge through an inhibition of PR phosphorylation/action but not PR expression.

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Section: Discussionsupporting

confidence: 91%

Immunoneutralization of Inhibin in Cycling Rats Increases Follicle-Stimulating Hormone Secretion, Stimulates the Ovary and Attenuates Progesterone Receptor-Dependent Preovulatory Luteinizing Hormone Secretion

Gordon

Aguilar²,

Garrido‐Gracia³

et al. 2010

Neuroendocrinology

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“…Although the FSH-dependent ovarian hormones inhibin (Culler 1992, Byrne et al 1995 and follistatin (Wang et al 1990) have been postulated to have GnSI/A bioactivity, the majority of evidence support the view that the inhibitory effect of exogenous FSH on the LH surge is mainly due to the activity of the putative GnSI/AF (de Koning et al 1987, Balen & Jacobs 1991, Balen 1996, Byrne et al 1996, de Koning et al 2001, Fowler et al 2003. GnSI/AF is a nonsteroidal, non-inhibin ovarian hormone of w60-70 kDa (Fowler et al 2003) secreted by granulosa cells in response to FSH with the specific bioactivity of inhibiting LHRH selfpriming (Balen 1996, Fowler et al 2003.…”

Section: Discussionmentioning

confidence: 99%

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

Gordon

Garrido‐Gracia

Aguilar

et al. 2007

Journal of Endocrinology

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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.

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“…In the rat, exogenous FSH increases and/or prolongs the bioactivity (secretion and/or action) of putative gonadotropin surge inhibiting/attenuating factor (GnSI/AF; de Koning 1995, Fowler et al 2003, Messinis 2006), a nonsteroidal and non-inhibin ovarian factor (Fowler et al 1993, 2003, Byrne et al 1995. GnSI/AF negatively regulates GNRH1-stimulated LH secretion (Tijssen et al 1997) and GNRH1 self-priming (Koppenaal et al 1991, Fink 1995.…”

Section: Introductionmentioning

confidence: 99%

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

Gordon¹,

Garrido‐Gracia²,

Aguilar³

et al. 2009

Reproduction

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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.

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Gonadotropin Surge-Attenuating Factor Bioactivity in Serum from Superovulated Women is not Blocked by Inhibin Antibody1

Cited by 21 publications

References 23 publications

Immunoneutralization of Inhibin in Cycling Rats Increases Follicle-Stimulating Hormone Secretion, Stimulates the Ovary and Attenuates Progesterone Receptor-Dependent Preovulatory Luteinizing Hormone Secretion

Immunoneutralization of Inhibin in Cycling Rats Increases Follicle-Stimulating Hormone Secretion, Stimulates the Ovary and Attenuates Progesterone Receptor-Dependent Preovulatory Luteinizing Hormone Secretion

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

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

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