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1 October 2003 Mechanisms of Action of Transforming Growth Factor β on the Expression of Follicle-Stimulating Hormone Receptor Messenger Ribonucleic Acid Levels in Rat Granulosa Cells
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Abstract

The present study was undertaken to identify the mechanisms underlying the effect of transforming growth factor (TGF) β on FSH receptor (FSH-R) in rat granulosa cells. Compared to the control, the treatment of granulosa cells with TGFβ (10 ng/ml) increased FSH-R mRNA transcripts (5.5 and 2.4 kilobases) in a time-dependent manner, with a maximum increase of approximately 2-fold at 48 h. We then investigated whether the effect of TGFβ on FSH-R mRNA levels was the result of increased transcription and/or altered mRNA stability. To determine whether the FSH-R 5′-flanking region plays a role in directing FSH-R mRNA expression, the proximal area of the FSH-R 5′-flanking regions were inserted into an expression vector, pGL-Basic, which contains luciferase as the receptor gene, and the resulting plasmids were transiently transfected into rat granulosa cells. The FSH (30 ng/ml) significantly enhanced the activity of 1862 base pairs of the FSH-R 5′-flanking region, but treatment with TGFβ did not significantly influence the activity induced by FSH. On the other hand, the decay curves for FSH-R mRNA transcript in primary granulosa cells showed a significant increase in half-life after the addition of TGFβ. Transforming growth factor β stimulates the expression of follistatin mRNA accumulation in a dose- and time-dependent manner. Treatment with activin produced a substantial increase in FSH-R mRNA level. Concurrent treatment with follistatin neutralized this activin effect on FSH-R mRNA, as reported, although concurrent treatment with follistatin did not affect TGFβ-induced FSH-R mRNA. Therefore, the profile of the TGFβ effect on FSH-R mRNA granulosa cells may be caused by the increased stability of FSH-R mRNA and insensitivity to the follistatin.

Kyoko Inoue, Kazuto Nakamura, Kazuko Abe, Takashi Hirakawa, Megumi Tsuchiya, Yuki Oomori, Hiroko Matsuda, Kaoru Miyamoto, and Takashi Minegishi "Mechanisms of Action of Transforming Growth Factor β on the Expression of Follicle-Stimulating Hormone Receptor Messenger Ribonucleic Acid Levels in Rat Granulosa Cells," Biology of Reproduction 69(4), 1238-1244, (1 October 2003). https://doi.org/10.1095/biolreprod.102.014753
Received: 20 December 2002; Accepted: 1 May 2003; Published: 1 October 2003
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