The effect of transforming growth factor-β on follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells

William Dodson, David W. Schomberg

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Growth factors have been shown to modulate differentiation of cultured ovarian granulosa cells. Transforming growth factors (TGFs) constitute a family of polypeptide growth factors capable of reversibly inducing anchorage-independent growth in normal cells. Epidermal growth factor (EGF), which has significant structural homology with TGF α, has been shown to modulate differentiation of granulosa cells in vitro. Similarly, TGFβ (TGFB) has been found to have significant structural homology with ovarian follicular fluid inhibin. To examine whether TGFB might affect granulosa cell growth or differentiation, rat granulosa cells were cultured in serumfree medium containing insulin for up to 3 days with varying concentrations of TGFB in the presence or absence of FSH. TGFB caused a dose-dependent increase in FSH-stimulated LH/hCG receptor binding, but had no effect on binding in the absence of FSH; TGFB (10.0 ng/ml) further increased FSHstimulated LH/hCG receptor binding by 48 ± 8% (P < 0.02). Similarly, FSH-stimulated progesterone production was increased by TGFB in a dose-dependent manner; TGFB (1.0–10.0 ng/ml) increased FSH-stimulated progesterone production 2- to 3-fold (P < 0.02). In contrast, EGF (10.0 ng/ml) decreased FSHstimulated LH/hCG receptor binding by 93 ± 1% (P < 0.02). Neither FSH-stimulated intracellular nor extracellular cAMP accumulations were affected by TGFB treatment. However, EGF (10.0 ng/ml) diminished extracellular and intracellular FSHstimulated cAMP accumulation at 48 and 72 h of culture. Culture protein and DNA content were not significantly affected by TGFB. These results suggest that 1) TGFB may enhance FSHstimulated LH receptor induction and steroidogenesis by mechanisms that do not further increase net cellular cAMP accumulation; 2) TGFB and EGF can have opposite effects on gonadotropin-dependent differentiation; and 3) products of the TGFB/ inhibin gene family may have a capacity for autocrine or paracrine modulation of granulosa cell differentiation.

Original languageEnglish (US)
Pages (from-to)512-516
Number of pages5
JournalEndocrinology
Volume120
Issue number2
DOIs
StatePublished - Jan 1 1987

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Granulosa Cells
Follicle Stimulating Hormone
Transforming Growth Factors
LH Receptors
Epidermal Growth Factor
Inhibins
Progesterone
Intercellular Signaling Peptides and Proteins
Follicular Fluid
Growth
Gonadotropins
Cell Differentiation
Insulin
Peptides
DNA
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

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title = "The effect of transforming growth factor-{\^I}² on follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells",
abstract = "Growth factors have been shown to modulate differentiation of cultured ovarian granulosa cells. Transforming growth factors (TGFs) constitute a family of polypeptide growth factors capable of reversibly inducing anchorage-independent growth in normal cells. Epidermal growth factor (EGF), which has significant structural homology with TGF {\^I}±, has been shown to modulate differentiation of granulosa cells in vitro. Similarly, TGF{\^I}² (TGFB) has been found to have significant structural homology with ovarian follicular fluid inhibin. To examine whether TGFB might affect granulosa cell growth or differentiation, rat granulosa cells were cultured in serumfree medium containing insulin for up to 3 days with varying concentrations of TGFB in the presence or absence of FSH. TGFB caused a dose-dependent increase in FSH-stimulated LH/hCG receptor binding, but had no effect on binding in the absence of FSH; TGFB (10.0 ng/ml) further increased FSHstimulated LH/hCG receptor binding by 48 {\^A}± 8{\%} (P < 0.02). Similarly, FSH-stimulated progesterone production was increased by TGFB in a dose-dependent manner; TGFB (1.0{\^a}€“10.0 ng/ml) increased FSH-stimulated progesterone production 2- to 3-fold (P < 0.02). In contrast, EGF (10.0 ng/ml) decreased FSHstimulated LH/hCG receptor binding by 93 {\^A}± 1{\%} (P < 0.02). Neither FSH-stimulated intracellular nor extracellular cAMP accumulations were affected by TGFB treatment. However, EGF (10.0 ng/ml) diminished extracellular and intracellular FSHstimulated cAMP accumulation at 48 and 72 h of culture. Culture protein and DNA content were not significantly affected by TGFB. These results suggest that 1) TGFB may enhance FSHstimulated LH receptor induction and steroidogenesis by mechanisms that do not further increase net cellular cAMP accumulation; 2) TGFB and EGF can have opposite effects on gonadotropin-dependent differentiation; and 3) products of the TGFB/ inhibin gene family may have a capacity for autocrine or paracrine modulation of granulosa cell differentiation.",
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The effect of transforming growth factor-β on follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells. / Dodson, William; Schomberg, David W.

In: Endocrinology, Vol. 120, No. 2, 01.01.1987, p. 512-516.

Research output: Contribution to journalArticle

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