Dopaminergic stimulation and inhibition of growth hormone secretion in normal man: studies of the pharmacologic specificity.
We have previously reported that dopamine (DA) stimulates basal GH secretion, but blunts the response to hypoglycemia. Because the pharmacological specificity of these dual actions has never been determined, a four-part study was undertaken. Before the administration of regular insulin (0.1 U/kg), male subjects received saline, DA or the DA agonist bromocriptine either alone or during dopaminergic blockade with metoclopramide. DA and bromocriptine increased GH levels comparably, and pretreatment with metoclopramide abolished this response [control, 2.9 +/- 0.7 (+/- SE); DA, 12.8 +/- 3.2 (P less than 0.01); bromocriptine, 13.0 +/- 3.4 (P less than 0.05); bromocriptine plus metoclopramide, 4.8 +/- 1.4 ng/ml (NS compared to control; P less than 0.05 compared to bromocriptine)]. Both DA and bromocriptine significantly inhibited the GH response to hypoglycemia [peak increment: control, 35.2 +/- 4.8; DA, 7.5 +/- 1.8 (P less than 0.001); bromocriptine, 13.7 +/- 3.2 ng/ml (P less than 0.05)], while pretreatment with metoclopramide restored GH secretion to normal (24.5 +/- 6.8; NS compared to control). Similar results were obtained comparing the mean GH peaks and areas under the curve. While there was no correlation in the hypoglycemic GH responses between the control and dopaminergic studies, the blunting effects of dopamine and bromocriptine were highly correlated (r = 0.93; P less than 0.001). Consequently, under basal conditions, DA and bromocriptine stimulate GH to a similar degree and diminish the GH response to hypoglycemia comparably. Pretreatment with the DA antagonist metoclopramide returns GH secretion to normal by preventing the increase after bromocriptine and restoring the hypoglycemia-medicated rise. Therefore, the dual actions of DA on GH secretion are mediated by a dopaminergic mechanism, since they are mirrored by a specific DA agonist and prevented by a DA antagonist.
D001786:Blood Glucose / Q000378:metabolism; D001971:Bromocriptine; D004298:Dopamine; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin; D007700:Kinetics; D008297:Male; D008787:Metoclopramide
D001786:Blood Glucose; D007328:Insulin; D001971:Bromocriptine; D013006:Growth Hormone; D008787:Metoclopramide; D004298:Dopamine