Expression and role of thyroid-stimulating hormone receptors in proopiomelanocortin-producing pituitary cells.

BACKGROUND Thyrotropin (TSH) is well known as the hormone of the anterior pituitary thyrotrophs responsible for acting in the thyroid gland, where it stimulates synthesis and release of thyroid hormones through Gs and Gq/11 protein coupled TSH receptors. METHODS Here we examined whether the functional TSH receptors are also expressed in cultured rat pituitary cells, using double immunocytochemistry, qRT-PCR analysis, cAMP and hormone measurements, and single cell calcium imaging. RESULTS Double immunocytochemistry revealed the expression of TSH receptors in cultured corticotrophs and melanotrophs, in addition to previously identified receptors in folliculostellate cells. The functional coupling of these receptors to the Gq/11 signaling pathway was not observed, as demonstrated by the lack of TSH activation of IP3-dependent calcium mobilization in these cells when bathed in calcium-deficient medium. However, TSH increased cAMP production in a time- and concentration-dependent manner and facilitated calcium influx in single corticotrophs and melanotrophs, indicating their coupling to Gs signaling pathway. Consistent with these findings, TSH stimulated adrenocorticotropin and β-endorphin release in male and female pituitary cells in a time and concentration-dependent manner without affecting the expression of proopiomelanocortin gene. CONCLUSIONS These results indicate that TSH is a potential paracrine modulator of anterior pituitary corticotrophs and melanotrophs, controlling the exocytotic but not the transcriptional pathway in a cAMP/calcium influx-dependent manner.