Introduction: Chronic dietary induced perinatal hypothyroidism results in a transient delay in Leydig cell and prolonged Sertoli cell proliferation in neonatal rat testes, hence the start of complete spermatogenesis is altered. In the present study we have investigated the possible role of thyroid hormone (TH) transporters and receptors (TR) in relation to the delayed onset of spermatogenesis. Methods: Hypothyroidism was induced in rats during fetal development by feeding dams an iodide-poor diet supplemented with 0.5% sodium perchlorate. Euthyroid controls received AIN-93-based regular rat chow. Results: Sertoli cells are targets for TH as they express TRa1. q-PCR analysis revealed that under hypothyroid conditions testicular expression of TRa1 is transiently increased until day 35 postpartum (pp). TRa2 followed a similar pattern, whereas TRß levels were too low to be quantified. Testicular TH levels have then been measured using LC-MS/MS. Our first results show that T4 levels have declined by more than 90% in hypothyroid testes. Strikingly, testicular rT3 levels were similar between the hypothyroid and control groups on day 28pp, while T3 levels were marginally decreased. Immunohistochemistry of the testis from day 12pp up to adulthood showed staining for TH transporter Lat2 in developing and adult Leydig cells, independent of the TH status. Lat2 staining is absent in the seminiferous tubule. Preliminary results from a Lat2 knockout mouse model show delayed Leydig and Sertoli cell development in the early adult testis. Conclusion: Although several TH transporter mouse models have shown that male offspring is fertile, we present indications that TH transporters play a pivotal role in the timely development of the Leydig cell population and the onset of complete spermatogenesis by contributing to maintenance of local supply with thyromimetically active T3 under hypothyroid conditions.
|Publication status||Published - 2013|
|Event||56th Symposium of the German Society of Endocrinology (DGE), Düsseldorf, Germany - |
Duration: 13 Mar 2013 → 16 Mar 2013
|Conference||56th Symposium of the German Society of Endocrinology (DGE), Düsseldorf, Germany|
|Period||13/03/13 → 16/03/13|