Role of growth hormone (GH)-releasing hormone and somatostatin in the mediation of clonidine-induced GH release in sheep.
GH secretion is stimulated by the administration of an alpha 2-adrenergic agonist, clonidine, in several species, including man. This action is probably mediated at the level of the hypothalamus, where the drug may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to collect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. Clonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorded during the same period. Next, we tested the effect of clonidine in sheep actively immunized against GHRH or SRIH. The alpha 2-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas immunization against SRIH did not modify the GH response. Finally, we observed that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect is mediated through changes in GHRH, but not SRIH, release into hypophysial portal blood.
Magnan
E
E
Laboratoire de Neuroendocrinologie Expérimentale, INSERM U-297, Institut Fédératif Jean Roche, Faculté de Médecine Nord, Marseille, France.
Cataldi
M
M
Guillaume
V
V
Mazzocchi
L
L
Dutour
A
A
Razafindraibe
H
H
Sauze
N
N
Renard
M
M
Oliver
C
C
D000818:Animals; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D013004:Somatostatin / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D003000:Clonidine