Regulation of thyroid hormones on the production of testosterone in rats

The effects of a thyroidectomy and thyroxine (T-4) replacement on the spont aneous and human chorionic gonadotropin (hCG)-stimulated secretion of testo sterone and the production of adenosine 3',5'-cyclic monophosphate (cAMP) i n rat testes were studied. Thyroidectomy decreased the basal levels of plas ma luteinizing hormone (LH) and testosterone, which delayed the maximal res ponse of testosterone to gonadotropin-releasing hormone (GnRH) and hCG in m ale rats. T-4 replacement in thyroparathyroidectomized (Tx) rats restored t he concentrations of plasma LH and testosterone to euthyroid levels. Thyroi dectomy decreased the basal release of hypothalamic GnRH, pituitary LH, and testicular testosterone as well as the LH response to GnRH and testosteron e response to hCG in vitro. T-4 replacement in Tx rats restored the in vitr o release of GnRH, GnRH-stimulated LH release as well as hCG-stimulated tes tosterone release. Administration of T-4 in vitro restored the release of t estosterone by rat testicular interstitial cells (TICs). The increase of te stosterone release in response to forskolin and androstenedione was less in TICs from Tx rats than in that from sham Tx rats. Administration of nifedi pine in vitro resulted in a decrease of testosterone release by TICs from s ham Tx but not from Tx rats. The basal level of cAMP in TICs was decreased by thyroidectomy. The increased accumulation of cAMP in TICs following admi nistration of forskolin was eliminated in Tx rats. T-4 replacement in Tx re stored the testosterone response to forskolin. But the testosterone respons e to androstenedione and the cAMP response to forskolin in TICs was not res tored by T-4 in Tx rats. These results suggest that the inhibitory effect o f a thyroidectomy on the production of testosterone in rat TICs is in part due to: 1) the decreased basal secretion of pituitary LH and its response t o GnRH; 2) the decreased response of TICs to gonadotropin; and 3) the dimin ished production of cAMP, influx of calcium, and activity of 17 beta-HSD. T -4 may enhance testosterone production by acting directly at the testicular interstitial cells of Tx rats, (C) 1999 Wiley-Liss, Inc.