Thyroid Hormone Role and Economy in the Developing Testis

Abstract

Thyroid hormones (TH) exhibit pleiotropic regulatory effects on growth, development, and metabolism, and it is becoming increasingly apparent that the developing testis is an important target for them. Testicular development is highly dependent on TH status. Both hypo- and hyperthyroidism affect testis size and the proliferation and differentiation of Sertoli, Leydig, and germ cells, with consequences for steroidogenesis, spermatogenesis, and male fertility. These observations suggest that an appropriate content of TH and by implication TH action in the testis, whether the result of systemic hormonal levels or regulatory mechanisms at the local level, is critical for normal testicular and reproductive function. The available evidence indicates the presence in the developing testis of a number of transporters, deiodinases and receptors that could play a role in the timely delivery of TH action on testicular cells. These include the thyroid hormone receptor alpha (THRA), the MCT8 transporter, the TH-activating deiodinase DIO2, and the TH-inactivating deiodinase DIO3, all of which appear to modulate testicular TH economy and testis outcomes.

Keywords: Antimullerian hormone; DIO1; DIO2; DIO3; Deiodinase; Estrogen; Follicle-stimulating hormone; Germ cells; Gonadal axis; Inhibin; Leydig cell; Luteinizing hormone; MCT8; OATP1C1; Sertoli cell; Spermatogenesis; Spermatogonia; Steroidogenesis; T3; T4; THRA; Testis; Testosterone; Thyroid hormone; Thyroid hormone receptors; Thyroid hormone transporter; Thyroxine; Triiodothyronine.