Rapid Changes in the Expression of Inhibin α-, βA-, and βB-Subunits in Ovarian Cell Types During the Rat Estrous Cycle

Meunier, Hélène; Cajander, Stefan; Roberts, Veronica J.; Rivier, Catherine; Sawchenko, Paul E.; Hsueh, Aaron J. W.; Vale, Wylie

doi:10.1210/mend-2-12-1352

Cited by 209 publications

(137 citation statements)

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“…It has been shown previously by Northern blot, in situ hybridisation and immunohistochemical analyses (Woodruff et al 1987, Meunier et al 1988, Jih et al 1993, Drummond et al 1996) that mRNA and protein, respectively, for the inhibin subunits ( , A and B ) are produced by ovarian granulosa cells, and inhibin immunoactivity and bioactivity have been measured in ovarian extracts and conditioned media collected from granulosa cell and ovarian cell cultures (Erickson & Hsueh 1978, Bicsak et al 1986, Suzuki et al 1987, Robertson et al 1988, Drummond et al 1996. It is still unclear, however, which of the biologically active forms produced by the ovary are responsible for the actions of inhibin and whether the production of the inhibin forms varies according to the stage of ovarian development or follicle type.…”

Section: Introductionmentioning

confidence: 78%

Temporal and hormonal regulation of inhibin protein and subunit mRNA expression by post-natal and immature rat ovaries

Drummond

Dyson

Thean

et al. 2000

Journal of Endocrinology

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The contribution of specific follicle populations to dimeric inhibin production and inhibin subunit mRNA expression by the rat ovary has been investigated in two model systems, granulosa cells isolated from 25-day-old diethylstilboestrol (DES)-treated rats and post-natal rat ovaries, dispersed in culture or whole ovaries, using specific two-site immunoassays and 'real time' PCR. Media from FSH-stimulated granulosa cell cultures fractionated by gel filtration and RP-high performance liquid chromatography revealed two predominant peaks of subunit activity which were attributed to subunit and 31 k dimeric inhibin-A. The corresponding inhibin-B levels were low. FSH stimulation did not alter the ratio of inhibin-A: subunit produced by granulosa cells. All three inhibin subunit mRNAs were expressed by granulosa cells, with eight-fold more subunit mRNA relative to either of the subunits. Administration of DES to immature rats prior to the isolation of granulosa cells from the ovary led to A and B mRNA expression being down-regulated in the absence of any significant change in subunit expression by the granulosa cells. Inhibin-A, -B and -subunit were produced by basal and stimulated cultures of ovarian cells prepared from 4-, 8-and 12-day-old rats, indicating that primary, preantral and antral follicles contribute to total inhibin production. Consistent with these results, follicles within these ovaries expressed all three inhibin subunit mRNAs, with maximal expression observed in the ovaries of 8-day-old rats. The appearance of antral follicles in the ovary at day 12 led to a decline in the mRNA levels of each of the subunits but was most evident for the subunits. There was a profound influence of secondary preantral follicles on dimeric inhibin-A production, with FSH stimulation increasing inhibin-A relative to subunit levels in cultures of ovarian cells prepared from 8-day-old rats. Thus, preantral follicles exposed to FSH contribute significantly to A subunit production by the ovary. In contrast, primary and preantral follicles did not produce inhibin-B in response to FSH stimulation. Transforming growth factor-(TGF-) enhanced, in a time-dependent manner, the production of the inhibin forms by ovarian cells in culture, although inhibin-B production was not responsive until day 8. The simultaneous treatment of ovarian cell cultures with FSH and TGF-elicited the greatest increases in production of all the inhibin forms.In summary, ovaries of 4-, 8-and 12-day-old rats expressed inhibin subunit mRNAs and produced dimeric inhibin-A and -B and free subunit. Preantral follicles (day-8 ovarian cell cultures) were particularly sensitive to stimulation by FSH and TGF-and had a substantial capacity for inhibin production. The production of oestrogen by follicles may be instrumental in regulating inhibin production given that subunit mRNA expression was down-regulated by DES. The mechanisms by which inhibin-A and inhibin-B are individually regulated are likely to be similar during the post-natal period, when folliculoge...

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Section: Introductionmentioning

confidence: 78%

Temporal and hormonal regulation of inhibin protein and subunit mRNA expression by post-natal and immature rat ovaries

Drummond

Dyson

Thean

et al. 2000

Journal of Endocrinology

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“…In the rat testis, the temporal expression of LHR and inhibin α-subunit protein appears to be similar as both can be detected in fetal Leydig cells as early as embryonic day 14 (Huhtaniemi, 1995;Majdic G et al, 1997;O'Shaughnessy et al, 1997). In the ovaries, the inhibin α-subunit promoter has been shown to direct transgene expression to theca and granulosa cells of secondary and preovulatory follicles (Meunier et al, 1988) whereas LHR is only present in the granulosa cells of preovulatory follicles (Richards, 1994). Therefore, in order to obtain a mouse model that is exactly like the human condition with the activating LHR mutations it will be necessary to faithfully mimic the cell specific and temporal expression of human LHR.…”

Section: Discussionmentioning

confidence: 97%

Constitutively active luteinizing hormone receptors: Consequences of in vivo expression

Meehan¹,

Narayan²

2007

Molecular and Cellular Endocrinology

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Activating mutations in the luteinizing hormone receptor (LHR) gene are one of the most common mutations found in the gonadotropin receptor genes. Human males with these mutations exhibit precocious puberty while females do not have an obvious phenotype. To better understand the pathophysiology of premature LHR activation, transgenic mice have been generated with an activating mutation in LHR and a genetically engineered ligand-activated LHR. This review will summarize the major findings obtained with these two genetically modified mouse models and briefly discuss the similarities and differences between them and with the human phenotype.

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“…Inhibin is a dimeric protein comprised of a unique subunit and one of the two activin subunits, to produce inhibin A ( A) or inhibin B ( B) (Robertson et al 1985, Esch et al 1987. In the rat, inhibin production is tightly regulated throughout the oestrous cycle (Meunier et al 1988, Woodruff et al 1988. In the ewe, after the preovulatory LH/FSH surge, inhibin A falls to a nadir coincident with the peak of the postovulatory FSH rise (Knight et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Activin and inhibin receptor gene expression in the ewe pituitary throughout the oestrous cycle

Fafioffe

Jf²,

Fontaine³

et al. 2004

Journal of Endocrinology

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In mammals, activin and inhibin are important regulators of FSH secretion. Previous studies have demonstrated that primary ovine pituitary cells express different activin receptor subtypes: activin receptor-like (ALK)2, ALK4, activin type II receptor A (ActRIIA), ActRIIB and Smad proteins in vitro. Here, we have carried out physiological studies to investigate the pattern of mRNA expression of the activin receptor subunits in the ewe pituitary throughout the oestrous cycle. The oestrous cycles of ewes were synchronized with progestagen sponges. The animals were killed 36 h (before the preovulatory surge, n=4), 48 h (during the preovulatory surge, n=4), 72 h (during the second surge of FSH, n=6) and 192 h (during the luteal phase, n=4) after sponge removal. Using Northern blots, we have shown that the levels of ALK2, ALK4 and ActRIIB mRNA were significantly higher before the preovulatory surge and during the secondary surge of FSH as compared with both during the preovulatory surge and the luteal phase, whereas the level of the ActRIIA mRNA was similar throughout the oestrous cycle. Using Western blots we have also demonstrated that the level of phosphoSmad2 did not vary during the reproductive cycle. Inhibin binding protein (InhBP/p120) and the transforming growth factor-type III receptor, betaglycan, have been identified as putative inhibin co-receptors. In this study, we cloned a fragment of both InhBP/p120 and betaglycan cDNAs in the ewe and showed by Northern blot that pituitary betaglycan and InhBP/p120 mRNA levels did not fluctuate across the oestrous cycle nor did they correlate with serum FSH levels.

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Rapid Changes in the Expression of Inhibin α-, βA-, and βB-Subunits in Ovarian Cell Types During the Rat Estrous Cycle

Cited by 209 publications

References 46 publications

Temporal and hormonal regulation of inhibin protein and subunit mRNA expression by post-natal and immature rat ovaries

Temporal and hormonal regulation of inhibin protein and subunit mRNA expression by post-natal and immature rat ovaries

Constitutively active luteinizing hormone receptors: Consequences of in vivo expression

Activin and inhibin receptor gene expression in the ewe pituitary throughout the oestrous cycle

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