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/10(6) cells, respectively (P less than 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.
To examine the mechanism by which obesity influences ovulation, 55 patients with oligo- or anovulation were studied. Parameters measured in serum were sex steroid-binding globulin (SSBG), testosterone (T), PRL, LH, FSH, and estradiol (E2). The women were divided into 2 groups: an obese group (group 1), greater than 145% of ideal body weight, and a normal weight group, less than 120% ideal body weight. SSBG was measured by saturation analysis T, LH, FSH, PRL, and E2 were measured by RIA. SSBG group 1 levels were 7.14 ng dihydrotestosterone bound/ml compared to 14.7 ng dihydrotestosterone bound/ml in group 2 (P less than 0.05). There were no significant differences in FSH, T, or E2. The correlation of body weight vs. SSBG in all patients was r = -0.62. In these 2 groups, the SSBG was significantly lower in the obese patients compared to that in the normal weight patients, independent of T or E2 levels. SSBG correlated negatively with body weight, suggesting that obesity has an influence on SSBG levels independent of hormonal status. When SSBG is lowered, there may be an increase in free T which, by inhibiting follicular maturation, may begin the sequence of events seen in polycystic ovary syndrome.
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