Effect of Estrogen on the Expression of Luteinizing Hormone-Human Chorionic Gonadotropin Receptor Messenger Ribonucleic Acid in Cultured Rat Granulosa Cells

Author:

Ikeda Sadatomo1,Nakamura Kazuto1,Kogure Kayoko1,Omori Yuki1,Yamashita Soichi1,Kubota Kazuko1,Mizutani Tetsuya23,Miyamoto Kaoru23,Minegishi Takashi1

Affiliation:

1. Department of Gynecology and Reproductive Medicine (S.I., K.N., K.K., Y.O., S.Y., K.K., T.Min.), Gunma University Graduate School of Medicine, Gunma 371-8511, Japan

2. Department of Biochemistry (T.Miz., K.M.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan

3. CREST (T.Miz., K.M.), Japan Science and Technology, Japan

Abstract

Estrogen has been considered to enhance FSH actions in the ovary, including the induction of the LH receptor (LHR). In this study, we elucidated the mechanism underlying the effect of estrogen on the induction of LHR by FSH in rat granulosa cells. Estradiol clearly enhanced the FSH-induced LHR mRNA increase in a time- and dose-dependent manner, with a maximum increase of approximately 3.5-fold at 72 h, compared with the level of LHR mRNA solely induced by FSH. We then investigated whether the effect of estrogen on LHR mRNA was due to increased transcription and/or altered mRNA stability. A luciferase assay with the plasmid containing the LHR 5′-flanking region did not show that estradiol increased the promoter activity induced by FSH. In contrast, the decay curves for LHR mRNA showed a significant increase in half-life with FSH and estradiol, suggesting that the increased stability of LHR mRNA is at least responsible for the regulation of LHR mRNA by estrogen. Recently mevalonate kinase (Mvk) was identified as a trans-factor that binds to LHR mRNA and alters LHR mRNA stability in the ovary. We found that estradiol, with FSH, decreased Mvk mRNA levels in rat granulosa cell culture, resulting in up-regulation of LHR mRNA that was inversely correlated to Mvk mRNA expression. Furthermore, the augmentation of FSH-induced LHR expression in the presence of estrogen was erased with the overexpression of Mvk by transient transfection. Taken together, these data indicate that LHR mRNA is up-regulated due to increased stability when estrogen negatively controls Mvk.

Publisher

The Endocrine Society

Subject

Endocrinology

Reference43 articles.

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