Dopaminergic inhibition of glycoprotein hormone α-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, α and β. In addition to producing intact hormone, the pituitary releases free α-subunit, which is stimulated by gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH). However, little is known about the dopaminergic regulation of free α-subunit in vivo. The effect of dopamine (DA), metoclopramide (MTC), and the specific DA D-1 receptor agonist, fenoldopam, on circulating α-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 μg/kg · min (n = 6). After 3 hours, 10 mg MTC was administered intravenously (IV). The high dose of DA significantly lowered α-subunit levels ( P < .05). No response to MTC was observed in any of the groups. Six women received glucose or DA infusion (4.0 μg/kg · min) for 18 hours. DA significantly reduced basal α-subunit levels compared with control infusion ( P < .05). MTC administration after 17 hours induced a significant increase in α-subunit levels on the day of DA infusion compared with control ( P < .05). In a third study, nine normal males received fenoldopam (0.5 μg/kg · min) or placebo infusions for 4 hours. Fenoldopam did not affect basal α-subunit levels, but the α-subunit response to a GnRH TRH bolus was significantly increased during fenoldopam compared with control ( P < .05). The results suggest that α-subunit release may be modulated by the dopaminergic system in vivo. This dopaminergic effect on α-subunit secretion resembles dopaminergic modulation of LH, rather than TSH secretion.