Evidence for a primary involvement of somatostatin in clonidine-induced growth hormone release in conscious rats.
The GH-releasing activity of the alpha 2-adrenergic agonist clonidine has been extensively studied in the rat, but the mechanism(s) by which clonidine stimulates GH release remains controversial. In the present study, we examined the effects of various doses of clonidine on spontaneous pulsatile GH secretion in conscious rats, and tested the hypothesis that the GH-releasing activity of clonidine is mediated primarily by an inhibition of hypothalamic somatostatin (SRIF) release. In the first experiment, free-moving adult male rats were given either saline or various doses of clonidine i.v. (30, 50 and 125 micrograms/kg) at times of spontaneous peaks (1100 h) and troughs (1300 h) in the GH rhythm. Clonidine, at all doses tested, failed to stimulate GH release when administered at the time of a spontaneous peak. In contrast, injection of clonidine at trough times (when SRIF tone is high) consistently augmented plasma GH levels (mean +/- S.E.M. integrated GH release; 30 micrograms/kg, 1843.0 +/- 484.0; 50 micrograms/kg, 1469.0 +/- 490.3; 125 micrograms/kg, 1675.6 +/- 513.4 vs 201.3 +/- 100.1 ng/ml per 45 min in saline-injected controls; p < 0.05 or less). No significant regression was observed between increasing doses of clonidine and GH release. In the second experiment, i.v. administration of 30 micrograms clonidine/kg during a GH trough period, 30 min prior to GH-releasing factor (GRF) challenge, significantly potentiated the GH response to GRF compared with rats given saline (7218.7 +/- 806.6 vs 4206.9 +/- 1068.1 ng/ml per 30 min; p < 0.05). Clonidine treatment, at all doses tested, resulted in hyperglycaemia and behavioural effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Lanzi
R
R
Department of Pediatrics, McGill University, Quebec, Canada.
Lapointe
M
M
Gurd
W
W
Tannenbaum
G S
GS
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*
D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D003000:Clonidine