CHARACTERIZATION OF ENDOTHELIN RECEPTORS IN THE ANTERIOR-PITUITARY GLAND

To characterize endothelin (ET) receptors modulating pituitary hormone secretion, potencies of ET-like agonists were compared on prolactin (PRL), thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) secretion from primary cultures of female rat pituitary cells. ET-1 was more potent than ET-3 in all cases. Sarafotoxin (SRFX) S6b an ET(A) agonist, was also more potent than ET-3 in all cases. SRTX-c, an ET(B) receptor agonist, was inactive. The ET-1-to-ET-3 potency ratio was three orders of magnitude higher on PRL or TSH secretion than on LH and FSH secretion, whereas SRTX-b-to-ET-3 potency ratios were similar on all four hormones. The ET(A) antagonist BQ-123 caused a parallel dextral displacement of dose-response curves of ET-1 and ET-3 on all four hormones. Schild regressions for BQ-123 on ET-1-induced PRL, TSH, LH, and FSH secretion indicated that BQ-123 has a similar affinity for the receptors mediating ET-1's effects. When BQ-123 was assessed against ET-3, Schild regressions indicated greater affinity for ET-3 on lactotrophs and thyrotrophs than gonadotrophs. Thus changes in pituitary hormone secretion are mediated by ET(A)-like receptors. ET receptors in lactotrophs and thyrotrophs are clearly distinguishable from gonadotrophs. We suggest the existence of distinct ET(A) receptor subtypes (ET(A1) and ET(A2)) on these differing pituitary cells.