Effects of bovine inhibin, transforming growth factor-β and bovine activin-A on granulosa cell differentiation

Hutchinson, Laura; Findlay, Jock K.; Vos, F.L. de; Robertson, David

doi:10.1016/0006-291x(87)90806-0

Cited by 217 publications

(88 citation statements)

References 13 publications

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“…However, this conflicts with a report on the effects of inhibin on ovine granulosa cells showing that inhibin A enhances FSH-induced oestradiol secretion, while inhibin antiserum has the reverse effect (Campbell & Baird 2001). Hutchinson et al (1987) reported that bovine inhibin A had no effect on FSH-induced steroid production by rat granulosa cells.…”

Section: Inhibin-activin Systemmentioning

confidence: 99%

“…However, the three TGF-b isoforms appear to induce similar effects, albeit with different potencies depending on the cell type studied . Similar to activin A, TGF-b can stimulate FSH receptor expression (Dunkel et al 1994), amplify FSH-induced aromatase activity, inhibin production, progesterone production and LH receptor induction (Hutchinson et al 1987, Zhang et al 1988, Kim & Schomberg 1989, Dorrington et al 1993, Drummond et al 2000. TGF-b has also been shown to suppress thecal P450c17 expression and androgen production, in a similar manner to activin A (Demeter-Arlotto et al 1993, Fournet et al 1996.…”

Section: Tgf-bmentioning

confidence: 99%

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TGF-β superfamily members and ovarian follicle development

Knight

Glister²

2006

Reproduction

1,048

786

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In recent years, exciting progress has been made towards unravelling the complex intraovarian control mechanisms that, in concert with systemic signals, coordinate the recruitment, selection and growth of follicles from the primordial stage through to ovulation and corpus luteum formation. A plethora of growth factors, many belonging to the transforming growth factor-b (TGF-b) superfamily, are expressed by ovarian somatic cells and oocytes in a developmental, stage-related manner and function as intraovarian regulators of folliculogenesis. Two such factors, bone morphogenetic proteins, BMP-4 and BMP-7, are expressed by ovarian stromal cells and/or theca cells and have recently been implicated as positive regulators of the primordial-to-primary follicle transition. In contrast, evidence indicates a negative role for anti-Mullerian hormone (AMH, also known as Mullerianinhibiting substance) of pre-granulosa/granulosa cell origin in this key event and subsequent progression to the antral stage. Two other TGF-b superfamily members, growth and differentiation factor-9 (GDF-9) and BMP-15 (also known as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play key roles in promoting follicle growth beyond the primary stage; mice with null mutations in the gdf-9 gene or ewes with inactivating mutations in gdf-9 or bmp-15 genes are infertile with follicle development arrested at the primary stage. Studies on later stages of follicle development indicate positive roles for granulosa cell-derived activin, BMP-2, -5 and -6, theca cell-derived BMP-2, -4 and -7 and oocyte-derived BMP-6 in promoting granulosa cell proliferation, follicle survival and prevention of premature luteinization and/or atresia. Concomitantly, activin, TGF-b and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection in monovular species may depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Changes in intrafollicular activins, GDF-9, AMH and several BMPs may contribute to this selection process by modulating both FSH-and IGF-dependent signalling pathways in granulosa cells. Activin may also play a positive role in oocyte maturation and acquisition of developmental competence. In addition to its endocrine role to suppress FSH secretion, increased output of inhibin by the selected dominant follicle(s) may upregulate LH-induced androgen secretion that is required to sustain a high level of oestradiol secretion during the pre-ovulatory phase. Advances in our understanding of intraovarian regulatory mechanisms should facilitate the development of new approaches for monitoring and manipulating ovarian function and improving fertility in domesticated livestock, endangered species and man.

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Section: Inhibin-activin Systemmentioning

confidence: 99%

Section: Tgf-bmentioning

confidence: 99%

TGF-β superfamily members and ovarian follicle development

Knight

Glister²

2006

Reproduction

1,048

786

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“…Activin has been isolated from follicular fluid and is known to have several actions that influence ovarian function [6][7][8][9][10][11][12][13], but its secretion by granulosa cells has not been reported previously. The present study demonstrated that porcine granulosa cells cultured alone for 6 days secreted activin together with inhibin and progesterone.…”

Section: Discussionmentioning

confidence: 99%

“…INHIBIN [1][2][3] and activin [4,5] have been isolated from mammalian follicular fluid and are known to have various intra-gonadal effects on follicular and luteal function [6][7][8][9][10][11][12][13]. Studies with both in vivo and in vitro systems [14] have established that FSH is the principal regulator of ovarian inhibin secretion, and studies with an N-terminal fragment RIA for the inhibin a-chain have confirmed that inhibin secretion from cultured rat granulosa cells is stimulated in a dosedependent manner by FSH and LH [15].…”

mentioning

confidence: 99%

Activin and Inhibin Secretion by Cultured Porcine Granulosa Cells is Stimulated by FSH and LH.

Demura¹,

Suzuki²,

Tajima³

et al. 1993

Endocr J

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Abstract. Follistatin-free activin and inhibin levels were measured in the culture medium of porcine granulosa cells by a competitive protein binding assay and N-fragment RIA, respectively. Cultures were maintained for 6 days in MEM containing 10% fetal calf serum. FSH and HCG (1-1,000 IU/L) were added on day 2 to cultures containing 1 x 105 cells/ml and the medium was changed every 2 days. Granulosa cells secreted a large amount of progesterone, which indicated their luteinization. Activin and Inhibin were both secreted throughout the 6 day culture period. Both of them increased equally in response to FSH and HCG in a dose-dependent manner on day 4, but their responses became discrepant on day 6, when the activin response decreased while the response of inhibin increased. This study demonstrated that cultured porcine granulosa cells secrete both activin and inhibin under the control of FSH and LH. The activin response was lost before that of inhibin, suggesting the role of activin at an earlier stage of luteinization. Likewise, it has been shown that FSH is a major regulator of activin, based on the observation that FSH stimulated f3-subunit mRNA by rat granulosa cells [18]. Variations in the expression of inhibin aor fl-subunits in the rat ovary during the estrous cycle suggested that there is a cyclic change in inhibin and/or activin in response to gonadotropins [19]. However, direct evidence has been lacking regarding the control of activin secretion from granulosa cells, because there has been no sensitive and specific assay for activin. We measured follistatin-free activin and inhibin levels in the culture medium of porcine granulosa cells under basal as well as gonadotropin-stimulated conditions by means of a newly developed activin assay that utilizes follistatin as a binding protein [20]. This study provided data on the regulation of activin and inhibin secretion and clarified a difference in their in vitro response to gonadotropins.

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“…In the ovaries of cyclic rats, levels of TGF 1 transcripts are rather low, but rise 12 h following an ovulatory dose of human chorionic gonadotropin, a rise which is sustained throughout the life of the corpus luteum when pregnancy ensues (Gaddy-Kurten et al 1989). In tissue culture systems, TGF has been shown significantly to alter the proliferation and differentiation of granulosa (Adashi & Resnick 1986, Feng et al 1986, Knecht et al 1986, Ying et al 1986, Dodson & Schomberg 1987, Hutchinson et al 1987, Skinner et al 1987, Adashi et al 1989) and theca-interstitial (Gangrade & May 1990, Hernandez et al 1990, Roberts & Skinner 1991 cells. In general, TGF 1 inhibits follicle cell growth and facilitates follicle cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-beta1 is a potent inhibitor of interleukin-1beta action in whole ovarian dispersates

Derman

Kol²,

Ben‐Shlomo³

et al. 1999

Journal of Endocrinology

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Transforming growth factor 1 (TGF 1 ) acts as an inhibitor of the actions of interleukin-1 (IL-1 ) in various organ systems. In order better to understand the interØactions between these polypeptides in the ovary, we evaluated the effect of TGF 1 co-treatment on various IL-1 -mediated actions in cultures of whole ovarian dispersates. Treatment with IL-1 enhanced media accumulation of nitrites (4·8-fold), prostaglandin E 2 (PGE 2 , 3·9-fold) and lactate (2·0-fold), and enhanced glucose consumption (2·1-fold). Treatment with TGF 1 alone did not significantly affect any of these parameters. However, the addition of TGF 1 inhibited IL-1 -stimulated nitrite (100%), PGE 2 (44%) and lactate (78%) accumulation and inhibited IL-1 -stimulated glucose consumption (74%) in a dose-dependent manner. The addition of TGF 1 also suppressed the steady-state levels of IL-1 -stimulated IL-1 , type I IL-1 receptor and IL-1 receptor antagonist transcripts (98, 67 and 83% inhibition respectively). These data suggest that TGF 1 is capable of inhibiting several IL-1 -stimulated endpoints. Since IL-1 has been identified as a possible proinflammatory mediator of ovulation and TGF has been implicated as a promotor of fibrosis and healing, we speculate that IL-1 and TGF might play antagonistic roles in the normal ovulatory sequence.

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Effects of bovine inhibin, transforming growth factor-β and bovine activin-A on granulosa cell differentiation

Cited by 217 publications

References 13 publications

TGF-β superfamily members and ovarian follicle development

TGF-β superfamily members and ovarian follicle development

Activin and Inhibin Secretion by Cultured Porcine Granulosa Cells is Stimulated by FSH and LH.

Transforming growth factor-beta1 is a potent inhibitor of interleukin-1beta action in whole ovarian dispersates

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