Activin Stimulation of Inhibin Secretion and Messenger RNA Levels in Cultured Granulosa Cells

LaPolt, Philip S.; Soto, Darya; Su, Jyan-Gwo J.; Campen, Carolyn A.; Vaughan, Joan; Vale, Wylie; Hsueh, Aaron J. W.

doi:10.1210/mend-3-10-1666

Cited by 109 publications

(38 citation statements)

References 40 publications

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“…These data showed that the levels of inhibin-A and subunit could be directly compared, which is perhaps not surprising given that the assays share a common standard and coating antibody. Gel filtration confirmed previously published observations (Bicsak et al 1988, LaPolt et al 1989 that the predominant inhibin forms in FSH-stimulated granulosa cell-conditioned media are 31 k inhibin and molecular weight forms of the subunit greater than 31 k. However, unlike Bicsak et al (1988), we were able to detect 31 k inhibin in basal granulosa cell-conditioned media (data not shown). This difference probably reflects the different methodologies employed and their relative sensitivities.…”

Section: Discussionsupporting

confidence: 91%

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: Discussionsupporting

confidence: 91%

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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“…This interpretation is supported by the strong correlation between activin A and either inhibin A or follistatin in all three gestational tissues, which suggest that the synthesis of these three polypeptides is regulated in a similar fashion in response to regulatory signals in these tissues. Indeed, activin itself may be the common link, since inhibin and follistatin synthesis and secretion have been shown to be regulated by activin in a number of tissues (La Polt et al 1989, Bilezikjian et al 1993, Song et al 1996.…”

Section: Discussionmentioning

confidence: 99%

Concentrations of activin A, inhibin A and follistatin in human amnion, choriodecidual and placental tissues at term and preterm

Keelan¹,

Marvin²,

Sato³

et al. 1999

Journal of Endocrinology

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To investigate labour-associated changes in production of activin and related hormones by gestational tissues we prepared extracts from amnion, choriodecidual and placental tissues delivered at term before labour (TNL; n=15), at term after spontaneous labour (TSL; n=15) or preterm (PTD; n=31) and measured concentrations of inhibin A, activin A and follistatin by ELISA. Activin concentrations in placental tissues were significantly (Mann-Whitney U-test; P<0·05) elevated with term labour (pg/mg protein, median; 1313 vs 2591), but in the PTD tissues concentrations were lower than those delivered spontaneously at term (3650 vs 2649). Inhibin concentrations also increased with term labour in the placenta (480 vs 686), but paradoxically decreased in amnion (188 vs 64) and choriodecidua (657 vs 358). Little or no significant changes in follistatin concentrations were observed. Concentrations of all three proteins were significantly correlated between amnion and choriodecidual tissues, and were significantly correlated with each other in most tissues (Spearman's ranked correlation; P<0·05). The activin:inhibin ratio in term amnion and choriodecidual tissues was increased 2 to 3-fold (P<0·0005 by MannWhitney U-test) after term labour, with similar trends also observed in the activin:follistatin ratio in placental tissue. These data suggest that a modest increase in placental activin and inhibin production may occur with labour at term. In addition, an increase in activin bioactivity may occur with labour, potentiating any paracrine effects of activin during parturition. The data, however, do not support an association between increased intrauterine activin biosynthesis and preterm delivery.

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“…The ACTH-induced shift from primarily DHAS production to increased cortisol production in the fetal zone is analogous to the shift in steroidogenesis that occurs postnatally. Activin (33). This difference may reflect species-specific, organ-specific, and/or developmentally dependent regulation ofsubunit production.…”

Section: Discussionmentioning

confidence: 99%

Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.

et al. 1992

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Recent experimental data have revealed that activins and inhibins exert pivotal effects on development. As part of our studies on growth and differentiation of the human fetal adrenal gland, we examined the subunit localization, as well as the mitogenic and steroidogenic actions of activin and inhibin in human fetal and adult adrenals. All three activin and inhibin subunit proteins (a, ,A, and #B) were detected in the fetal and adult adre-

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Activin Stimulation of Inhibin Secretion and Messenger RNA Levels in Cultured Granulosa Cells

Cited by 109 publications

References 40 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

Concentrations of activin A, inhibin A and follistatin in human amnion, choriodecidual and placental tissues at term and preterm

Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.

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