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Human Chorionic Gonadotropin Up-Regulates Insulin-Like Growth Factor-I Receptor Gene Expression of Leydig Cells^*

Medical and Research Services, W. J. B. Dorn Veterans Hospital, and Department of Medicine, University of South Carolina School of Medicine Columbia, South Carolina 29208

Address requests for reprints to: Tu Lin, M.D., Medical Service, W. J. B. Dorn Veterans Hospital, Columbia, South Carolina 29201.

Abstract

The effects of hCG, 8-bromo-cAMP, 4β-phorbol 12β-myristate 13-acetate, and forskolin on insulin-like growth factor-I (IGF-I) receptor gene expression of Leydig cells were studied. The treatment of purified Leydig cells with hCG caused a dose-dependent increase in [¹²⁵I]IGF-I binding to Leydig cells without changes in binding affinity, indicating that the increased binding was due to increased receptor numbers and not to increased affinity. The minimal time required for hCG to induce IGF-I binding was 6 h, and it had reached a plateau at 16 h. 8- Bromo-cAMP (1 mM) increased IGF-I binding about 2-fold, and forskolin (10 µM) increased binding about 51%. Using the ribonuclease protection assay, we found that hCG and 8-bromo-cAMP could increase IGF-I receptor mRNA expression as early as 2 h before the increase in IGF-I binding. The induction by hCG was over 3.5-fold at 4 h and decreased to about 2-fold at 6 h. 4β- Phorbol 12β-myristate 13-acetate had a very small effect on IGF-I receptor mRNA levels (1.5-fold increase at 2 h and no changes at 4 and 6 h). In conclusion, IGF-I receptors can be upregulated by hCG, 8-bromo-cAMP, and forskolin. The up-regulation of IGF-I receptor number is associated with transient increases in IGF-I receptor mRNA levels. This could be a mechanism by which hCG and IGF-I interact to enhance Leydig cell steroidogenesis. (Endocrinology 129: 2820–2826,1991)

Footnotes

^* This work was supported by the V.A. Medical Research Fund and NIH 1RO1-HD-25641-03 (to T.L.).

Received June 29, 1991.

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