Dopaminergic inhibition of glycoprotein hormone alpha-subunit in normal subjects

Abstract

The pituitary glycoprotein hormones thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) consist of two noncovalently linked subunits, alpha and beta. In addition to producing intact hormone, the pituitary releases free alpha-subunit, which is stimulated by gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH). However, little is known about the dopaminergic regulation of free alpha-subunit in vivo. The effect of dopamine (DA), metoclopramide (MTC), and the specific DA D-1 receptor agonist, fenoldopam, on circulating alpha-subunit levels was studied in normal men and women. Normal women received 4-hour infusions of either glucose (n = 6) or DA at rates of 0.04 (n = 6), 0.4 (n = 6), and 4.0 micrograms/kg.min (n = 6). After 3 hours, 10 mg MTC was administered intravenously (IV). The high dose of DA significantly lowered alpha-subunit levels (P less than .05). No response to MTC was observed in any of the groups. Six women received glucose or DA infusion (4.0 micrograms/kg.min) for 18 hours. DA significantly reduced basal alpha-subunit levels compared with control infusion (P less than .05). MTC administration after 17 hours induced a significant increase in alpha-subunit levels on the day of DA infusion compared with control (P less than .05). In a third study, nine normal males received fenoldopam (0.5 microgram/kg.min) or placebo infusions for 4 hours. Fenoldopam did not affect basal alpha-subunit levels, but the alpha-subunit response to a GnRH/TRH bolus was significantly increased during fenoldopam compared with control (P less than .05). The results suggest that alpha-subunit release may be modulated by the dopaminergic system in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)