Portal de Periódicos da CAPES

Follicle-Stimulating Hormone Receptor Expression in the Rat Ovary: Increases during Prepubertal Development and Regulation by the Opposing Actions of Transforming Growth Factors β and α1

1994; Oxford University Press; Volume: 50; Issue: 4 Linguagem: Inglês

10.1095/biolreprod50.4.940

1529-7268

Leo Dunkel, Jonathan L. Tilly, Toshihiko Shikone, K Nishimori, Aaron J.W. Hsueh,

TGF-β signaling in diseases

Pituitary gonadotropin FSH acts exclusively on ovarian granulosa cells by binding to specific plasma membrane receptors. Transforming growth factors α and ß (TGFα and TGFβ), produced locally within the ovary, have been shown to regulate diverse follicle functions, although their potential role in the regulation of FSH receptors has not been assessed. Our first objective was to demonstrate developmental changes in the expression of FSH receptor gene and protein; we then analyzed the regulation of FSH receptor expression by TGFβs and TGFα in cultured granulosa cells. Analysis of steady-state FSH receptor mRNA and protein levels in neonatal and prepubertal ovaries revealed the existence of two predominant FSH receptor mRNA transcripts, 7.0 and 2.5 kb in size, showing a dramatic increase between Day 15 and Day 18 of age followed by a plateau up to 27 days of age. A close parallelism in the developmental changes in FSH receptor mRNA levels and FSH receptor content was observed. Cultured granulosa cells obtained from estrogen-treated immature rats exhibited FSH receptor transcripts similar in size to those seen in whole ovaries. Treatment of granulosa cells for 48 h with TGFβ1 increased the levels of FSH receptor mRNA for both the 7.0- and 2.5-kb transcripts in a dose-dependent manner (ED50, 1.5 ng/ml), with a maximal 4.0 ± 0.8-fold increase over control levels observed in response to 10 ng/ml TGFβ1. Also, TGFβ2 was as potent as TGFβ1 in increasing FSH receptor mRNA levels. In contrast, treatment of granulosa cells for 48 h with TGFα (10 ng/ml) decreased the basal FSH receptor mRNA level by 65 - 5% (p < 0.05). Furthermore, treatment with TGFα dose-dependently attenuated the stimulatory action of TGFβ1 or TGFβ2 on FSH receptor mRNA levels (ID50 for TGFα, 1.5 ng/ml). A complete suppression of TGFβ action was observed in response to the highest dose of TGFα used (p < 0.01). Radioligand binding analysis in granulosa cells further indicated that treatment with 10 ng/ml TGFβ1 or TGFβ2 alone significantly (p < 0.01) increased the number of FSH binding sites, indicating that the observed modulation of FSH receptor mRNA levels by TGFβs is associated with changes in FSH receptor content. Treatment with TGFα attenuated the stimulatory action of TGFβ1 or TGFβ2 on the number of FSH receptors; this was consistent with the ability of TGFα to suppress TGFβ-stimulated increase in FSH receptor mRNA levels. Thus, treatment of granulosa cells with TGFβ1 or TGFβ2 increases the steady-state level of FSH receptor mRNA as well as the expression of the receptor protein. The actions of TGFβs are antagonized by TGFα. It is postulated that these growth factors are involved in the differentiation of granulosa cells by modulating FSH receptor gene expression.