Testosterone Increases TSH-β mRNA, and Modulates α-Subunit mRNA Differentially in Mouse Thyrotropic Tumor and Castrate Rat Pituitary

Summary

TSH, LH and FSH, the three pituitary glycoprotein hormones, are each composed of a common α-subunit and a hormone specific β-subunit. Testosterone is known to regulate all three intact hormones differently in the rodent. However, there is only one gene encoding the common α-subunit. In order to elucidate the effects of testosterone on TSH subunit synthesis and its regulation of the common α-subunit, two in vivo models were studied: castrate rat pituitary was used as a gonadotropin-enriched tissue; and mouse thyrotropic tumor was used as a thyrotropin-enriched tissue. Male castrate rats were treated with testosterone propionate, 500 μg/100 g BW, sc, for 11 days. Testosterone increased plasma TSH to 131% of control values (P < 0.02), while plasma LH fell to undetectable levels, and plasma α-subunit fell to 14% of control values (P < 0.001). Testosterone increased TSH-β mRNA to 237% of control values (P < 0.02), while α-subunit mRNA fell to 20% of control values (P < 0.001). Hypothyroid mice bearing thyrotropic tumors were treated with testosterone propionate, 150 μg/100 g BW, sc, for 11 days. In this model plasma TSH-β and α-subunit concentrations are 1000-fold higher than in non-tumor bearing animals, and the contribution of pituitary gonadotropes to plasma subunit concentrations is negligible. “Total” TSH-β and α-subunit concentrations were estimated as one-half of intact TSH plus the respective free subunit concentration. Testosterone increased plasma total TSH-β to 169% (P < 0.05) and total α-subunit to 164% (P < 0.05) of control values, respectively. Testosterone increased tumor TSH-β mRNA to 176% of control values (P < 0.05), while an increase in α-subunit mRNA concentration was not statistically significant.

The androgen-mediated increase in plasma TSH concentrations is accompanied by an increase in thyrotrope TSH-β mRNA concentration. Since testosterone reduces gonadotropin-enriched castrate pituitary α-subunit mRNA levels, the unchanged concentrations of α-subunit mRNA within the thyrotropic tumor after testosterone administration suggests a possible cell-specific effect of testosterone on the single common α-subnit gene.

Key words

TSH - Testosterone - Thyrotropic Tumor