Role of GnRH in the regulation of pituitary GnRH receptors in female mice

Naik, Sharda; Young, L. S.; Saade, G.; Kujore, A.; Charlton, H. M.; Clayton, Richard N.

doi:10.1530/jrf.0.0740605

Cited by 18 publications

(13 citation statements)

References 15 publications

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“…None of these treatments hpg mice led to detectable serum LH concentrations. However, as previously observed (Naik et al, 1985 ; Text-fig. 1), serum LH but not serum FSH in intact and ovariectomized normal female mice was markedly suppressed by multiple GnRH injections (Group 2 vs Group 1, < 0-05 ; Group 41« Group 3, < 0-001) and there was a reduction of pituitary LH content in ovariectomized females (P < 005).…”

Section: Introductionsupporting

confidence: 86%

Evidence for a pituitary site of gonadal steroid stimulation of GnRH receptors in female mice

Naik¹,

Young²,

Charlton³

et al. 1985

Reproduction

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Treatment of GnRH-deficient (hpg) female mice with oestradiol-17\g=b\(E2) for 7 days increased GnRH receptors from 4\m=.\1\ m=+-\0\m=.\4fmol/pituitary (control) to 7\m=.\2\ m=+-\ 0\ m=. \ 7 fmol/pituitary (GnRH-treated), and consistently increased pituitary FSH content. Treatment of hpg female mice with E2 plus progesterone (P) for 14 days stimulated GnRH receptors more than did E2 alone, although values still remained lower than those of normal intact female mice. In contrast, GnRH treatment of intact hpg female mice alone, or combined with E2 + P, increased GnRH receptors to values similar to those of intact normal female mice. In contrast, the receptor rise after GnRH treatment alone of ovariectomized hpg mice was significantly less than in intact hpg mice similarly treated. However, the combination of GnRH + E2 + P treatment of ovariectomized hpg mice increased GnRH receptors to normal intact female values, indicating the synergistic actions of these hormones on GnRH receptor up-regulation at the pituitary.Oestradiol treatment of ovariectomized normal female mice prevented the receptor fall after ovariectomy, and when combined with exogenous GnRH further increased receptors to values identical to those of intact female mice receiving GnRH alone.Ovariectomy of hpg mice had no effect on GnRH receptor, serum or pituitary LH and FSH values. There was no change in serum LH concentration after GnRH treatment of hpg female mice, but serum FSH increased and this was accentuated by ovariectomy, indicating that in intact mice an ovarian factor(s) normally inhibits GnRH-stimulated FSH release. This factor did not appear to be an ovarian steroid since serum FSH was not suppressed in intact or ovariectomized GnRH-treated hpg mice concurrently receiving E2 + P treatment.These results suggest that: (1) gonadal steroids alone have a major direct stimulatory action on the pituitary to increase GnRH receptors; (2) the oestrogen\x=req-\ induced increase in GnRH receptors is enhanced in the presence of GnRH; (3) steroids exert inhibitory feedback on gonadotrophin secretion that is mediated at some cellular regulatory locus other than the GnRH-receptor complex.

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Section: Introductionsupporting

confidence: 86%

Evidence for a pituitary site of gonadal steroid stimulation of GnRH receptors in female mice

Naik¹,

Young²,

Charlton³

et al. 1985

Reproduction

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“…60, 61). The main drivers of Gnrhr expression are GnRH itself (62)(63)(64), steroid hormones (64,65), and activins (14). GnRH and activin regulation of GnRHR protein expression in primary rat pituitary cultures appears to involve distinct, but complementary, mechanisms (13,66,67).…”

Section: Activin Induction Of Murine Gnrhr Transcriptionmentioning

confidence: 99%

“…They also do not ovulate and lack corpora lutea, suggesting that their progesterone levels are also low. In mice, GnRHR levels depend on both GnRH and gonadal steroids (62,63,116). Therefore, loss of steroid negative feedback and consequent increased GnRH release will not lead to up-regulated GnRHR levels (as they do in rats), if steroid levels are below a certain threshold level.…”

Section: The Combined Activities Of Foxl2 and Smad4 Are Required For mentioning

confidence: 99%

Minireview: Activin Signaling in Gonadotropes: What Does the FOX say… to the SMAD?

Fortin

Ongaro

et al. 2015

Molecular Endocrinology

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The activins were discovered and named based on their abilities to stimulate FSH secretion and FSHβ (Fshb) subunit expression by pituitary gonadotrope cells. According to subsequent in vitro observations, activins also stimulate the transcription of the GnRH receptor (Gnrhr) and the activin antagonist, follistatin (Fst). Thus, not only do activins stimulate FSH directly, they have the potential to regulate both FSH and LH indirectly by modulating gonadotrope sensitivity to hypothalamic GnRH. Moreover, activins may negatively regulate their own actions by stimulating the production of one of their principal antagonists. Here, we describe our current understanding of the mechanisms through which activins regulate Fshb, Gnrhr, and Fst transcription in vitro. The activin signaling molecules SMAD3 and SMAD4 appear to partner with the winged-helix/forkhead transcription factor, forkhead box L2 (FOXL2), to regulate expression of all 3 genes. However, in vivo data paint a different picture. Although conditional deletion of Foxl2 and/or Smad4 in murine gonadotropes produces impairments in FSH synthesis and secretion as well as in pituitary Fst expression, Gnrhr mRNA levels are either unperturbed or increased in these animals. Surprisingly, gonadotrope-specific deletion of Smad3 alone or with Smad2 does not impair FSH production or fertility; however, mice harboring these mutations may express a DNA binding-deficient, but otherwise functional, SMAD3 protein. Collectively, the available data firmly establish roles for FOXL2 and SMAD4 in Fshb and Fst expression in gonadotrope cells, whereas SMAD3's role requires further investigation. Gnrhr expression, in contrast, appears to be FOXL2, SMAD4, and, perhaps, activin independent in vivo.

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“…Administration of steroid hormones: Estradiol-17β, progesterone, glucocorticoid and testosterone (Sigma Chemical Co. St Louis, MO) dissolved in soybean oil were intraperitoneally administered to the gonadectomized transgenic mice daily for 10 days after they had reached 2 months of age, with reference to the doses of previous reports [20][21][22].…”

Section: Methodsmentioning

confidence: 99%

A Transgenic Mouse Model for Investigating the Response of the Upstream Region of Whey Acidic Protein (WAP) Gene to Various Steroid Hormones

et al. 2001

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Abstract:The limitations of studies of clarification of response elements of whey acidic protein (WAP) gene to hormones using mammary cell lines has been shown. We studied the response of the upstream region (2.6 kb) of WAP to various steroid hormones using gonadectomized mWAP/hGH transgenic mice. Ovariectomy or castration for transgenic mice was performed at 10 days or 30 days post partum. Various steroid hormones were administered daily for 10 days to the gonadectomized transgenic mice after they reached 2 months of age. Prior to the hormonal administration and 24 hr after the final administration, blood was collected and the hGH levels in the plasma was measured by RIA. Daily doses of estradiol-17β were significantly more effective at increasing hGH levels in transgenic females ovariectomized at 10 days post partum than progesterone of an equal dose. A combined dose of progesterone and of estradiol-17β significantly amplified the increase of hGH levels accompanied by the great development of mammary glands, compared to a dose of progesterone alone. Corticosterone induced only a slight increase of hGH, while testosterone had no effect. The doses of gonadal steroid hormones did not induce an increase in hGH levels and development of mammary glands in the castrated transgenic males. The results showed that the response of 5' region of WAP requires at least some extended development of the mammary gland and that the 2.6 kb upstream region of the exogenous WAP gene contained the element responsive to ovarian hormones.

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Role of GnRH in the regulation of pituitary GnRH receptors in female mice

Abstract: Summary. The fall in pituitary GnRH receptors in female mice after ovariectomy (Ovx)

Cited by 18 publications

References 15 publications

Evidence for a pituitary site of gonadal steroid stimulation of GnRH receptors in female mice

Evidence for a pituitary site of gonadal steroid stimulation of GnRH receptors in female mice

Minireview: Activin Signaling in Gonadotropes: What Does the FOX say… to the SMAD?

A Transgenic Mouse Model for Investigating the Response of the Upstream Region of Whey Acidic Protein (WAP) Gene to Various Steroid Hormones

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