α-Adrenergic inhibition of thyrotropin-releasing hormone-induced prolactin secretion in GH 4C 1 cells is associated with a depressed rise in intracellular Ca 2+

Abstract

α-Adrenergic receptors are present on the plasma membrane of normal anterior pituitary cells and α-adrenergic agonists may play a role in the secretion of corticotropin (ACTH) and thyrotropin (TSH). However, α-adrenergic involvement in prolactin (PRL) secretion is uncertain. We have therefore examined this question in the PRL-secreting clonal rat pituitary tumor-derived GH 4C 1 cells. Norepinephrine (NE), an α-adrenergic agonist, had no effect on basal PRL secretion but abolished thyrotropin-releasing hormone (TRH)-induced PRL secretion in a dose-dependent manner (EC 50 100 nM). NE also significantly suppressed the TRH-stimulated rise in [Ca 2+] i. Phentolamine (PA), a non-selective α-adrenergic antagonist, reversed the inhibitory effect of NE on both the TRH-stimulated PRL secretion and [Ca 2+] i rise. NE did not inhibit the rise in PRL secretion or [Ca 2+] i induced by depolarizing 30 mM K +, 30% hyposmolarity or BAY K-8644, a specific L-type Ca 2+ channel agonist. The inhibitory effect of NE on TRH-induced PRL and [Ca 2+] i changes was also present when Ca 2+ influx was prevented by removing medium Ca 2+ or by blocking L-type Ca 2+ channels with 2 μM nifedipine. The TRH-stimulated first-phase rise in [Ca 2+] i in GH 4C 1 cells is believed to result primarily from release of sequestered Ca 2+ from an intracellular pool through the activation of inositol 1,4,5-tri-sphosphate (IP 3) and this [Ca 2+] i spike stimulates PRL secretion. Our data thus suggest that GH 4C 1 cells have α-adrenergic receptors and that α-adrenergic agonists either suppress IP 3 generation or block IP 3 release of sequestered intracellular Ca 2+.