Evidence of dopamine receptors in human growth hormone (GH)-secreting adenomas with concomitant study of dopamine inhibition of GH secretion in a perifusion system.
Dopamine (DA) is known to influence human GH release both in vivo and in vitro. The direct control of GH secretion at the pituitary level has been observed using human GH-secreting pituitary adenomas in organ culture, but no dose-response relationship between DA and GH inhibition was demonstrated. Such a dose-response relationship was obtained using GH-secreting adenomatous cells in a perifusion column. The IC50 of DA was 5 X 10(-8) M. Binding studies with [3H]apomorphine on human GH-secreting pituitary adenoma membranes demonstrated the presence of a dopaminergic receptor (Kd = 0.73 +/- 0.24 nM; maximum binding, 18.5 +/- 3.6 fmol/mg protein), which presumably mediates the effect of DA on GH release. In comparison to prior studies with PRL-secreting adenomas, several differences were apparent: 1) the maximum inhibition of GH release by DA is lower than that of PRL (50% vs. 80%), 2) the maximum number of binding sites is much lower (5-20 times) in GH-secreting adenomas than in PRL-secreting adenomas, and 3) [3H]domperidone does not show specific binding on GH-secreting adenomas but does on PRL-secreting adenomas. These experimental results indicate that the dopaminergic control of GH secretion is different from that of PRL secretion, as DA is less effective on GH release than on PRL release from human pituitary adenomas.
D000236:Adenoma / Q000378:metabolism*; D001058:Apomorphine / Q000378:metabolism; D004294:Domperidone / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D010477:Perfusion; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*
D011954:Receptors, Dopamine; D004294:Domperidone; D013006:Growth Hormone; D001058:Apomorphine; D004298:Dopamine