α1-Adrenergic Receptors Mediate LH-Releasing Hormone Secretion through Phospholipases C and A2 in Immortalized Hypothalamic Neurons

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 α1-adrenergic receptors (α1-ARs). With the immortalized hypothalamic LHRH neurons, we have found that α1-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 α1A- and α1B-ARs. Competition binding experiments show that approximately 75% of the binding is due toα 1B-ARs; the remainder is made up ofα 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 PLA2 (cPLA2) and release arachidonic acid. A dissection of the contributions of the phospholip...