Pharmacological manipulations of alpha-adrenoceptors in the infant rat and effects on growth hormone secretion. Study of the underlying mechanisms of action.

Abstract

The aim of this study was to evaluate whether in infant rats, as in adult rats, the brain adrenergic mechanisms regulate plasma GH levels and, if so, to determine the contribution of GH-releasing hormone (GHRH) and/or somatostatin (SS) pathways. In 10-day-old rats, activation of alpha 2-adrenoceptors by clonidine (CLO) was effective to stimulate GH release starting from 50 micrograms/kg ip and up to 450 micrograms/kg ip, though no dose-related effect was evident. Conversely, alpha 2-adrenoceptor blockade by yohimbine (YOH, 10 mg/kg, ip) decreased baseline GH levels. Administration of methoxamine (METHOX, 10 micrograms/rat, ip), a alpha 1-adrenoceptor agonist, significantly reduced plasma GH concentrations, while prazosin (5 mg/kg BW, ip), a specific alpha 1-adrenoceptor antagonist, stimulated plasma GH secretion. Administration of an anti-SS serum (SS-ab, 300 microliters, ip) induced a significant rise in plasma GH levels, while administration of an anti-GHRH serum (GHRH-ab, 100 microliters, ip) was associated with a striking fall in GH levels. In rats pretreated with SS-ab, administration of CLO induced a further rise in plasma GH levels. GHRH-ab significantly reduced plasma GH levels, and this effect was not altered by subsequent CLO administration. Administration of SS-ab and YOH resulted in plasma GH levels intermediate between those of rats treated with SS-ab alone or YOH alone, while pretreatment with GHRH-ab induced a lowering of plasma GH greater than when YOH was given alone. in rats pretreated with SS-ab, the GH-lowering effect of METHOX was completely lacking, while GHRH-ab and METHOX induced a lowering of plasma GH similar to that ensuing after METHOX alone or GHRH-ab alone. Administration of prazosin in rats pretreated with SS-ab did not elicit any further rise in plasma GH, while combined administration with GHRH-ab elicited a GH-lowering effect comparable to that elicited by GHRH-ab alone. These data demonstrate that in the infant rat: brain adrenergic mechanisms involved in the neural regulation of GH secretion are operative; different neuropeptide mechanisms mediate the effect of activation or inhibition of alpha 1- and alpha 2-adrenoceptors. In particular, activation of alpha 2-adrenoceptors stimulates GH secretion via endogenous GHRH release, although a mechanism operating to inhibit hypothalamic SS release cannot be excluded; stimulation of alpha 1-adrenoceptors is inhibitory to GH secretion exclusively via an increased release of hypothalamic SS.