Effect of the benzodiazepine derivative, diazepam, on the clonidine-stimulated human growth hormone secretion.
gamma-Aminobutyric acid (GABA) has both stimulatory and inhibitory effect on human GH secretion. We previously reported that the benzodiazepine derivative diazepam, which exerts its main pharmacological effect by facilitating GABA-mediated transmission, is able to reduce the GH response to L-dopa and apomorphine. To establish whether diazepam affects the alpha-adrenergic regulation of GH secretion, the GH response to clonidine (an alpha-agonist) was investigated in seven volunteers after placebo and diazepam premedications. After placebo pretreatment, clonidine (0.15 mg iv infused over 20 min) significantly stimulated GH secretion: the mean serum GH level rose from a basal level of 4.7 +/- 1.1 (+/- SEM) ng/ml to a maximum of 10.8 +/- 1.6 ng/ml (P less than 0.025). After 3 days of diazepam treatment, a similar GH response to clonidine was observed; the mean serum GH level rose from a basal value of 2.3 +/- 0.3 ng/ml to a maximum of 9.4 +/- 1.3 ng/ml. It is concluded that the inhibitory effect of diazepam on human GH secretion is mediated via inhibition of dopaminergic transmission, whereas the alpha-adrenergic control of GH release is not affected. Since diazepam potentiates GABAergic transmission, its effect may reflect the role of endogenous GABA in human GH secretion.
D000328:Adult; D003000:Clonidine / Q000008:administration & dosage*; D003975:Diazepam / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors
D013006:Growth Hormone; D003000:Clonidine; D003975:Diazepam