[Ambivalent effect of thyroxine on the expression of gonadotropin genes in normal and orchidectomized rats]

In order to examine the role of thyroid hormones on pituitary gonadotropin synthesis and release, normal, thyroidectomized and orchidectomized male rats were treated in parallel by daily injections of thyroxine (10 micrograms/10 g). Pituitary levels of alpha, LH beta, FSH beta and TSH beta mRNA were determined using two complementary approaches: 1) cell-free translation of pituitary mRNA and quantitative immunoprecipitation of labeled subunit precursors, and 2) hybridization with [32P]-labeled cDNA probes. In intact and thyroidectomized rats, injection of thyroxine (T4) resulted in the depletion of all mRNAs encoding the glycoprotein hormone subunits. In contrast, when rats received T4 three weeks after orchidectomy, levels of alpha, LH beta- and FSH beta-mRNA, but not TSH beta-mRNA increased, by 2, 1.5 and 1.2 times, respectively, compared to castrated, sham-injected rats. LH was assayed in serum and pituitary. In intact rats, T4 decreased pituitary content and release of LH by about 25%. In castrated rats, T4 antagonized the gonadectomy-induced increase in serum LH and increased the pituitary content in LH to levels consistent with an increased synthesis. In conclusion, T4 treatment increases or decreases levels of translatable mRNA encoding all 3 gonadotropin subunits depending on whether rats were castrated or not, respectively. Thus, T4 appears to exert a modulatory role in the regulation of gonadotropin gene expression by steroids. This effect of T4 on the synthesis is discordant with the effects of T4 on the release of LH and probably involves complex, multimodal control mechanisms.