Dear Ayman,

The following publications might be helpful in covering the answer to your question.

1-BIOLOGY OF REPRODUCTION 50, 940-948 (1994)

Follicle-Stimulating Hormone Receptor Expression in the Rat Ovary: Increases during 

Prepubertal Development and Regulation by the Opposing Actions of Transforming

Growth Factors and &'

LEO DUNKEL, JONATHAN L. TILLY, TOSHIHIKO SHIKONE, KEIJI NISHIMORI, and AARON J.W. HSUEH 2

Division of Reproductive Biology, Department of Gynecology and Obstetrics

Stanford University School of Medicine, Stanford, California 94305-5317

ABSTRACT

Pituitary gonadotropin FSH acts exclusively on ovarian granulosa cells by binding to specific plasma membrane receptors. Transforming growth factors a and fA (TGFoa and TGFO), 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 TGFBs and TGFa 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 TGFOI1 increased the levels of FSH receptor mRNA for both the 7.0-

and 2.5-kb transcripts in a dose-dependent manner (ED,,, 1.5 ng/ml), with a maximal 4.0 0.8-fold increase over control levels observed in response to 10 ng/ml TGFI1. Also, TGFB2 was as potent as TGF1l in increasing FSH receptor mRNA levels. In contrast, treatment of granulosa cells for 48 h with TGFoa (10 ng/ml) decreased the basal FSH receptor mRNA level by 65 - 5% (p < 0.05). Furthermore, treatment with TGFot dose-dependently attenuated the stimulatory action of TGFP1 or TGFS2 on FSH receptor mRNA levels (ID5o for TGFoa, 1.5 ng/ml). A complete suppression of TGFOI action was observed in response to the highest dose of TGFt used (p < 0.01). Radioligand binding analysis in granulosa cells further indicated that treatment with 10 ng/ml TGF[I or TGF2 alone significantly (p < 0.01) increased the number of FSH binding sites, indicating that the observed modulation of FSH receptor mRNA levels by TGFps is associated with changes in FSH receptor content. Treatment with TGFe attenuated the stimulatory action of TGFi1 or TGFU2 on the number of FSH receptors; this was consistent with the ability of

TGFoa to suppress TGFP-stimulated increase in FSH receptor mRNA levels. Thus, treatment of granulosa cells with TGFP1 or TGF2 increases the steady-state level of FSH receptor mRNA as well as the expression of the receptor protein. The actions of TGFIs are antagonized by TGFot. It is postulated that these growth factors are involved in the differentiation of granulosa cells by modulating FSH receptor gene expression.

2-Life Sci. 1997;61(14):1435-43.

Effect of phorbol ester on the regulation of LH/hCG receptors.

Nakamura K1, Minegishi T, Tano M, Kishi H, Kameda T, Miyamoto K.

Author information

Abstract

Granulosa cells have been used to study the regulation of LH/hCG receptor protein and mRNA expression. Phorbol 12-myristate 13-acetate (PMA) dose-dependently attenuates the increases in LH/hCG receptor mRNA and protein induced by FSH and forskolin (FSK). The presence of PMA caused a decrease in cAMP production stimulated by FSH and FSK. These results suggest that PMA-mediated decreases in cAMP are a major factor in PMA-mediated decreases in LH/hCG receptor mRNA. On the other hand, in the presence of 8-Br-cAMP, PMA significantly increased LH/hCG receptor mRNA and protein, with maximal stimulation between PMA concentrations of 3 to 30 nM (1.5 fold) with 8-Br-cAMP. These findings suggest that activation of protein kinase C by PMA attenuates the increase in cAMP accumulation induced by FSH but enhances the effect of cAMP on LH/hCG receptor expression, and that the inhibitory and stimulatory effects of PMA on LH/hCG receptor content are correlated with regulation of LH/hCG receptor mRNA levels. Since the half-life study revealed no change in the stability of the LH/hCG receptor mRNA following PMA treatment, a change in the rate of LH/hCG receptor gene transcription must be responsible for the change in the LH/hCG receptor mRNA levels

3-The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology

Manuela Simoni, Jörg Gromoll, and Eberhard Nieschlag

http://press.endocrine.org/doi/full/10.1210/edrv.18.6.0320

DOI: http://dx.doi.org/10.1210/edrv.18.6.0320

First Published Online: July 01, 2013

I. Introduction

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Abstract

I. Introduction

Certainly in cattle the old grind and bind studies conducted by Ireland, Roche and Spicer tell the same story for gonadotropin receptors in follicles as the newer RNA  / gene expression studies led by HA Garverick, and his post doc Bagna Bao.