Effect of acute and chronic administration of clonidine on hypothalamic content of growth hormone-releasing hormone and somatostatin in the rat.
Hypothalamic GH-releasing hormone (GHRH) and somatostatin contents were determined in male rats at pre- and mid-pubertal stages following acute (0.15 mg/kg) or chronic (0.1 mg/kg twice daily for 7 days) administration of clonidine. Hypothalamic GHRH content increased markedly during transition from pre- to mid- and late-pubertal stages (2.05 +/- 0.17 vs 3.13 +/- 0.26 and 3.46 +/- 0.20 ng/hypothalamus respectively, means +/- S.E.M.). Hypothalamic GHRH content was markedly decreased 1 h after clonidine administration in mid-pubertal but not in prepubertal rats (3.67 +/- 0.23 vs 2.65 +/- 0.22 ng/hypothalamus). Hypothalamic somatostatin content, on the other hand, decreased in both age groups, although the decrease in the mid-pubertal group was more pronounced (51% and 38% respectively). In addition, the GH responsiveness to clonidine was higher at mid-puberty than at prepuberty. Determination of hypothalamic somatostatin and GHRH content in the chronic experiment 4 h after the last drug administration revealed a marked decrease in GHRH in the mid-pubertal rats and a slight decrease in the prepubertal rats (1.78 +/- 0.32 vs 3.15 +/- 0.31 and 2.01 +/- 0.30 vs 2.35 +/- 0.15 ng/hypothalamus; P less than 0.005 and P less than 0.05 respectively) whereas somatostatin levels were not altered. It is suggested that the clonidine-induced GH secretion is modulated by a chain of events which involves primary stimulation of GHRH release resulting in increased GH secretion which, via a negative-feedback mechanism, triggers an enhancement of somatostatin release which ultimately normalizes the system. This mechanism is age-dependent and reaches full maturity only at the onset of puberty.
Institute of Pediatric and Adolescent Endocrinology, Beilinson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tiqva, Israel.
I
I
Gil-Ad
Z
Z
Laron
Y
Y
Koch
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage*; D005246:Feedback / Q000502:physiology; D013006:Growth Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism*
D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D003000:Clonidine