Regulation of episodic growth hormone secretion by the central epinephrine system. Studies in the chronically cannulated rat.
Catecholamines are postulated to regulate growth hormone (GH) secretion by their influence on the release of two hypothalamic substances, somatostatin, which inhibits GH release, and GH-releasing factor, as yet unidentified. Extensive pharmacologic studies in man and animals indicate a stimulatory effect of central norepinephrine and dopamine on GH, but the function of epiphephrine (EPI) is uncertain. Furthermore, many of the agents used to study the role of catecholamines in GH regulation are not selective in that they affect adrenergic as well as nor-adrenergic and/or dopaminergic neurotransmission. In the present investigation, central nervous system (CNS) EPI biosynthesis was selectively interrupted with the specific norepinephrine N-methyltransferase inhibitors, SK & F 64139 (Smith, Kline & French Laboratories) and LY 78335, (Eli Lilly & Co. Research Laboratories) and the effects of central EPI depletion on episodic GH secretion in the chronically cannulated rat model were determined. Inhibition of CNS EPI synthesis with SK & F 64139 caused complete suppression of episodic GH secretion and concomitantly reduced the EPI level in the hypothalamus without affecting dopamine or norepinephrine. Administration of LY 78335 produced similar effects on pulsatile GH. Morphine-induced, but not clonidine-induced, GH release also was blocked by SK & F 64139. These results indicate that (a) the central EPI system has a major stimulatory function in episodic GH release, (b) morphine-induced GH release is mediated by the central EPI system, and (c) clonidine stimulates GH release by activation of postsynaptic alpha-adrenergic receptors. Drugs that affect CNS adrenergic systems have a potential role in the diagnosis and treatment of disorders of GH secretion.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010507:Periodicity; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D044005:Tetrahydroisoquinolines
D000588:Amines; D001596:Benzylamines; D007546:Isoquinolines; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines; C018428:1,2,3,4-tetrahydroisoquinoline-7-sulfonamide; C002569:2,3-dichloro-alpha-methylbenzylamine; D009020:Morphine; D011388:Prolactin; D013006:Growth Hormone; C012153:7,8-dichloro-1,2,3,4-tetrahydroisoquinoline; D010625:Phenylethanolamine N-Methyltransferase; D003000:Clonidine; D004837:Epinephrine