alpha(1)-adrenergic receptors mediate LH-releasing hormone secretion through phospholipases C and A(2) in immortalized hypothalamic neurons

Norepinephrine has long been known to stimulate the pulsatile and preovulat ory release of LH-releasing hormone (LHRH). In vivo and in vitro studies in dicate that these effects are mediated primarily through alpha (1)-adrenerg ic receptors (alpha (1)-ARs). With the immortalized hypothalamic LHRH neuro ns, we have found that alpha (1)-adrenergic agents directly stimulate the s ecretion of LHRH in a dose-dependent manner. Ligand binding and RNA studies demonstrate that the GT1 cells contain both alpha (1A)- and alpha (1B)-ARs . Competition binding experiments show that approximately 75% of the bindin g is due to alpha (1B)-ARs; the remainder is made up of alpha (1A)-ARs. Rec eptor activation leads to stimulation of PLC.PLC beta1 and PLC beta3 are ex pressed in GT1 neurons, and these PLCs are probably responsible for the rel ease of diacylglycerol and IP as well as the increase in intracellular calc ium. The mobilization of cytoplasmic calcium is sufficient to stimulate cyt osolic PLA(2) (cPLA(2)) and release arachidonic acid. A dissection of the c ontributions of the phospholipases to LHRH secretion suggests that cPLA(2) acts downstream of PLC and that it significantly augments the PLC-stimulate d LHRH secretory response. Inasmuch as the alpha (1)-ARs are known to play a critical role in LHRH physiology, we propose that both PLC and cPLA(2) ar e critical in regulating and amplifying LHRH release.