Endocrine Abstracts

Thyroid-stimulating hormone receptor (TSHR) is typically known to be expressed in the thyroid gland of mammals for the control of body metabolism. However, because the TSHR ancestor is the only glycoprotein hormone receptor found in invertebrates, we hypothesized that TSHR evolves much earlier than FSHR and LHR and thus can be expressed in mammalian gonads for certain uncharacterized impacts. To prove this, real-time PCR quantification against Tshr in all male mouse reproductive organs was performed. The results indicated, that Tshr is mainly expressed in the testis where it is increased in an age-dependent manner. TSHR is located mainly in Sertoli cells and moderately in germ cells; such a profile was further confirmed using isolated primary mouse Sertoli cells. Gene regulatory test using the TM4 Sertoli cell line showed that Tshr expression can be increased via the cAMP cascade. In terms of the cognate ligands for TSHR, we demonstrated that the testicular TSHR is likely to be activated via an endocrine loop by the pituitary-secreted TSH since the negligible level of the genes encoding TSH or thyrostimulin can be detected in male reproductive organs. Furthermore, using cultured testis tubules or explants, TSH treatment can not only promote the proliferation of germ cells ex vivo but also increase the transcripts of Tgn, Tpo and Slc5a5. Taken together, activation of the TSHR signaling in situ can influence spermatogenesis and may potentially regulate the amounts of thyroid hormones locally. Therefore, our findings overthrow the traditional concept regarding the physiological roles of TSHR and may open a new era of TSHR functions in the reproductive system.