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Follicle-Stimulating Hormone Suppresses Cytosolic 3,5,3'-Triiodothyronine-Binding Protein Messenger Ribonucleic Acid Expression in Rat Granulosa Cells

Department of Chemistry (N.A.G., I.J., T.H.J.) and Department of Clinical Sciences (C.K.), University of Kentucky, Lexington, Kentucky 40506

Address all correspondence and requests for reprints to: Dr. Tae H. Ji, Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055. E-mail: tji{at}uky.edu.

FSH plays crucial roles in differentiation of granulosa cells and development of follicles. Considering the broad scope of FSH effects, a large number of genes are likely responsive to the hormone. However, only a limited number of genes have been identified as FSH-regulated genes, particularly during the preantral stage. In an attempt to better define genes involved in follicular development, we examined primary granulosa cell cultures, an undifferentiated rat ovarian granulosa cell line and rat ovaries, using differential display, quantitative RT-PCR, Northern blot analysis, and in situ hybridization. We report, for the first time, that nicotinamide adenine dinucleotide phosphate-dependent cytosolic T₃-binding protein mRNA is expressed in the ovary, particularly in the granulosa cell layer of preantral and early antral follicles, but not in large preovulatory follicles. Its expression markedly declines in response to FSH, which is dependent on the period of the exposure. This FSH-responsive down-regulation is dependent on granulosa cell differentiation and follicular development. FSH down-regulates the mRNA via the adenylyl cyclase/cAMP pathway, and the down-regulation requires de novo synthesis of a regulatory protein(s). The cytosolic T₃-binding protein may play a significant role in the regulation of steroidogenesis and follicular development in the mammalian ovary.

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