Functional Studies of Dopamine Control of Prolactin Secretion in Normal Women and Women with Hyperprolactinemic Pituitary Microadenoma*

Abstract

Functional studies of the dopamine[D]-PRL [prolactin] system in the control of the secretory activity of the lactotrope were conducted in 8 normal cycling women during the early follicular phase of the cycle and in 14 hyperprolactinemic patients with pituitary microadenoma (prolactinoma). Dynamic changes in PRL release in response to D infusion and a D receptor antagonist [metoclopramide (MCP)], singly and in combination, were determined and compared between normal women and prolactinoma patients. The degree of D inhibition of PRL (via 4-h infusion) in prolactinoma patients was significantly greater in terms of both the absolute PRL decrement and the rate of PRL decline compared to normal women. A strong positive correlation (r = 0.964) was found between basal PRL levels and the magnitude of PRL decline during D infusion. The rebound PRL release above basal levels after D withdrawal was significantly smaller in prolactinoma patients than in normal women. In response to MCP alone, prolactinoma patients exhibited only 1/8 the PRL increment observed in normal women; once substantial inhibition of PRL release was achieved in prolactinoma patients (via D infusion), the D receptor antagonistic function of MCP (interposed during the 3rd h of D infusion) was restored. In normal women, the consequence of this D-D antagonist interaction on PRL release was manifested by a significant reduction in the magnitude of PRL release due to MCP and a significant increase in the rate as well as the magnitude of PRL release upon D withdrawal when compared with the response to either experiment alone. Thus, the sensitivity of the normal lactotrope to D inhibition changed markedly when its action was interrupted by the D-receptor antagonist. The rate of PRL rise after D withdrawal in prolactinoma patients was similarly increased, but the magnitude of PRL increments was smaller. Hypothalamic D in humans apparently constitutes a major PRL-inhibiting hormone, and the inhibitory function of D on lactotrope PRL release is a tightly punctuated system. The adenoma lactotrope appears to be capable of recognizing both D and its antagonist, implying functionally intact D receptors; reduced receptor-binding affinity for D cannot be excluded. The hypersecretion of PRL in prolactinoma patients is causally related, at least in part, to a relative local deficiency of D at the receptor site of the adenoma lactotrope.