Multiple factors affect prolactin secretion (Fig. 20-1). However, the principal influence on prolactin secretion is tonic inhibition by dopamine input from the hypothalamus. Dopamine interaction with receptors of the D2 subtype on pituitary lactotroph membranes activates the inhibitory G-protein, leading to decreased adenylate cyclase activity and decreased levels of cyclic adenosine monophosphate (cAMP). In prolactin-secreting pituitary adenomas, a monoclonal population of prolactin-producing cells escapes the normal physiologic input of dopamine from the hypothalamus, apparently by acquiring a peripheral blood supply. In almost all cases, responsiveness to a pharmacologic dose of dopamine is maintained.

The normal serum prolactin level is less than 15 or 30 ng/mL, depending on the laboratory. Women tend to have slightly higher levels than men, probably because of estrogen stimulation of prolactin secretion. In patients with prolactin-secreting tumors, the levels are usually higher than 100 ng/mL but may be as low as 30 to 50 ng/mL if the tumor is small. A level greater than 200 ng/mL is almost always indicative of a prolactin-secreting tumor. Very high prolactin levels may be found to be falsely normal because of the high-dose hook effect of the assay; if clinically indicated, the sample should be assayed again after dilution.

The most important physiologic states in which prolactin is found to be elevated are pregnancy and lactation. During the third trimester of pregnancy, the prolactin level may reach 200 to 300 ng/mL. It then gradually decreases during the first week postpartum, despite continued lactation, but may continue to rise acutely at the time of breastfeeding. Prolactin values are also elevated during sleep, strenuous exercise, stress, and nipple stimulation. In these cases, the elevation is mild, below 50 ng/mL.

See Table 20-1.

In all these cases, the prolactin value is usually mildly elevated, 30 to 50 ng/mL, and rarely above 100 ng/mL.