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 preovulatory release of LH-releasing hormone (LHRH). In vivo and in vitro studies indicate that these effects are mediated primarily through alpha(1)-adrenergic receptors (alpha(1)-ARs). With the immortalized hypothalamic LHRH neurons, we have found that alpha(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 alpha(1A)- and alpha(1B)-ARs. Competition binding experiments show that approximately 75% of the binding is due to alpha(1B)-ARs; the remainder is made up of alpha(1A)-ARs. Receptor activation leads to stimulation of PLC. PLC beta 1 and PLC beta 3 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 alpha(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.
Kreda
S M
SM
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Sumner
M
M
Fillo
S
S
Ribeiro
C M
CM
Luo
G X
GX
Xie
W
W
Daniel
K W
KW
Shears
S
S
Collins
S
S
Wetsel
W C
WC
D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D008024:Ligands; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*
D008024:Ligands; D020033:Protein Isoforms; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D016718:Arachidonic Acid; D007987:Gonadotropin-Releasing Hormone; D010741:Phospholipases A; D010738:Type C Phospholipases; D002118:Calcium