Interaction between norepinephrine and serotonin in the neuroendocrine control of growth hormone release in the rat.
Both alpha 2-adrenergic (alpha 2) and serotonergic (5HT) neurons are associated with stimulation of GH secretion via GRH release. The object of this study was to determine whether the 5HT system is involved in the stimulation of GH secretion by alpha 2-receptor agonists. There are two parts of this study. In the first, the relationship between alpha 2-5HT systems were analyzed by determining if alpha 2-stimulated GH release is mediated by 5HT. In this model, systemically administered alpha 2-agonists [clonidine (CLON) or UK14,304] were tested against 5HT antagonists (meterogoline or cyproheptadine) or 5HT synthesis inhibitors (p-chlorophenylalanine methylester hydrochloride). In the second, sites of 5HT-GRH interaction were determined by testing the response to CLON after 5HT neurotoxin [5,7-dihydroxytryptamine (5,7-DHT)] microinjection at specific hypothalamic nuclei. In both experiments sequential blood samples were withdrawn from silastic jugular cannulas in unanesthetized, freely moving animals. Metergoline (0.045 and 0.135 mg/kg, iv) and cyproheptadine (0.969 micrograms/kg, iv) suppressed, in a dose-dependent manner, the CLON (33 or 66 micrograms/kg, iv)-induced GH surge that was detected 15-30 min after injection in control animals. Both cyproheptadine (0.969 micrograms/kg, iv) and p-chlorophenylalanine (300 mg/kg, ip) effectively suppressed the UK14,304 (220 micrograms/kg, iv)-induced GH surge that occurred 15-30 min after injection in control animals. These data suggest that an intact 5HT system is required for alpha 2-stimulated GH release. 5,7-DHT neurotoxin microinjected into the midline arcuate nucleus (6 micrograms/mg,iv) or bilaterally into the ventromedial nucleus or perifornical area (4 micrograms/0.2 microliter) 5 days previously suppressed the CLON (30 micrograms/kg)-induced GH surge only in animals with arcurate nucleus lesions. To determine if the suppression was mediated by inhibition of GH-releasing hormone (GRH) or stimulation of somatostatin (SRIF), an additional experiment was conducted including 5,7-DHT arcuate nucleus-lesioned animals injected with anti-SRIF. Inasmuch as anti-SRIF failed to reverse the 5,7-DHT suppression of GH secretion, the results of this experiment suggest that GRH mediates NE-5HT-induced GH secretion. In conclusion, these data suggest that alpha 2 activation of GH secretion requires intact serotonergic terminals in the arcuate nucleus and most likely involves GRH rather than SRIF, release.
Conway
S
S
Department of Biological Sciences, Northern Illinois University, DeKalb 60115.
Richardson
L
L
Speciale
S
S
Moherek
R
R
Mauceri
H
H
Krulich
L
L
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D012702:Serotonin Antagonists; D008711:Metergoline; C020261:4-chlorophenylalanine methyl ester; D003533:Cyproheptadine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000068438:Brimonidine Tartrate; D006897:Hydroxyindoleacetic Acid; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D003000:Clonidine; D010134:Fenclonine; D009638:Norepinephrine