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Inhibition of Sex Hormone-Binding Globulin Production in the Human Hepatoma (Hep G2) Cell Line by Insulin and Prolactin^*

STEPHEN R. PLYMATE, LOUIS A. MATEJ, ROBERT E. JONES and KARL E. FRIEDL

Department of Clinical Investigation, Madigan Army Medical Center Tacoma, Washington 98431-5454

Sex hormone-binding globulin (SHBG) production in humans has been thought to be stimulated by estrogens and thyroid hormone and inhibited by androgens. However, recent data indicate that SHBG production in vitro is stimulated by both androgens and estrogens. This study was designed to determine what other hormonal factors regulate SHBG production. Since hyperinsulinemia and hyperprolactinemia both occur in disease states in which low serum SHBG levels are found, the effects of insulin and PRL were compared to and/or studied in combination with estradiol (E₂,) T₄, and testosterone (T) in a human hepatoma cell line (Hep G2). Hep G2 cells were grown to near confluence in medium including 10% fetal calf serum, and then 72-h experimental incubations were carried out which used only fetal calf serum-free medium. Compared to control incubations, both insulin (10^–8 mol/L) and PRL (10^–8 mol/L) decreased SHBG production from 65.0 ± 0.6 (±SE) to 46.8 ± 1.1 and 46.8 ± 1.2 nmol/108 cells, respectively (P < 0.01). Insulin also inhibited both E₂ and T₄-stimulated SHBG production. T stimulated SHBG production to the same degree as E₂. Finally, both E₂ and insulin significantly increased cell number, an important consideration when expressing the effect of a hormone on SHBG production in cultured cells. We conclude that insulin and PRL inhibit SHBG production and confirm that T₄, T, and E₂ stimulate SHBG production in vitro. These findings suggest that insulin and PRL may be important factors in the regulation of SHBG production in vivo. (J Clin Endocrinol Metab 67: 460, 1988)

^* The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense. These data have been presented in part at the Second International Symposium on Binding Proteins, Torino, Italy, 1987.

To whom requests for reprints should be addressed.

Received October 26, 1987.

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				J. E. Nestler and D. J. Jakubowicz Decreases in Ovarian Cytochrome P450c17{alpha} Activity and Serum Free Testosterone after Reduction of Insulin Secretion in Polycystic Ovary Syndrome N. Engl. J. Med., August 29, 1996; 335(9): 617 - 623. [Abstract] [Full Text] [PDF]

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				E. Diamanti-Kandarakis, G. Tolis, and A. J. Duleba Androgens and Therapeutic Aspects of Antiandrogens in Women Reproductive Sciences, July 1, 1995; 2(4): 577 - 592. [Abstract] [PDF]