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Endocrinology, doi:10.1210/endo-120-2-512
Endocrinology Vol. 120, No. 2 512-516
Copyright © 1987 by the Endocrine Society.
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The Effect of Transforming Growth Factor-β on Follicle-Stimulating Hormone-Induced Differentiation of Cultured Rat Granulosa Cells*

WILLIAM C. DODSON and DAVID W. SCHOMBERG

Departments of Obstetrics and Gynecology and Physiology, Duke University Medical Center Durham, North Carolina 27710

Address requests for reprints to: William C. Dodson, Box 3527, Duke University Medical Center, Durham, North Carolina 27710.

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 {alpha}, 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. (Endocrinology 120: 512–516, 1987)

Footnotes

* Presented in part at the 68th Annual Meeting of The Endocrine Society, Anaheim, CA, June 26-28, 1986. This work was supported in part by a grant from the Josiah Charles Trent Memorial Foundation and Grant HD-11827 from the NICHHD, NIH.

Received June 11, 1986.




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