α1-Adrenergic receptors mediate LH-releasing hormone secretion through phospholipases C and A2 in immortalized hypothalamic neurons

Journal Article

Norepinephrine has long been known to stimulate the pulsatile and preovulatory release of LH-releasing hormone (LHRH). In vivo and in vitro studies indicate that these effects are mediated primarily through α 1 -adrenergic receptors (α 1 -ARs). With the immortalized hypothalamic LHRH neurons, we have found that α 1 -adrenergic agents directly stimulate the secretion of LHRH in a dose-dependent manner. Ligand binding and RNA studies demonstrate that the GT1 cells contain both α 1A - and α 1B -ARs. Competition binding experiments show that approximately 75% of the binding is due to α 1B -ARs; the remainder is made up of α 1A -ARs. Receptor activation leads to stimulation of PLC. PLCβ1 and PLCβ3 are expressed in GT1 neurons, and these PLCs are probably responsible for the release of diacylglycerol and IP as well as the increase in intracellular calcium. The mobilization of cytoplasmic calcium is sufficient to stimulate cytosolic PLA 2 (cPLA 2 ) and release arachidonic acid. A dissection of the contributions of the phospholipases to LHRH secretion suggests that cPLA 2 acts downstream of PLC and that it significantly augments the PLC-stimulated LHRH secretory response. Inasmuch as the α 1 -ARs are known to play a critical role in LHRH physiology, we propose that both PLC and cPLA 2 are critical in regulating and amplifying LHRH release.

Full Text

Duke Authors

Cited Authors

  • Kreda, SM; Sumner, M; Fillo, S; Ribeiro, CM; Luo, GX; Xie, W; Daniel, KW; Shears, S; Collins, S; Wetsel, WC

Published Date

  • November 12, 2001

Published In

Volume / Issue

  • 142 / 11

Start / End Page

  • 4839 - 4851

International Standard Serial Number (ISSN)

  • 0013-7227

Digital Object Identifier (DOI)

  • 10.1210/en.142.11.4839

Citation Source

  • Scopus