Studies of dopaminergic mechanisms in hyperprolactinemic states.

Results are presented of studies of pharmacologic agents that modify dopaminergic function in subjects with diverse hyperprolactinemic states including prolactin-secreting tumors (PST) idiopathic hyperprolactinemia (IH) and chronic renal failure (CRF) and among postpartum women. The studies were conducted in 22 normal subjects including 15 women and 7 men; 33 patients with PST 11 of whom were studied before and after adenomectomy; 15 IH patients; 20 patients with CRF 14 of whom received maintenance hemodialysis and 6 after renal transplants; and 6 women 2-4 days postpartum. Protocols called for administration of L-dopa and carbidopa dopamine hydrochloride bromocriptine apomorphine and metoclopramide. In normal subjects plasma prolactin was suppressed by L-dopa to 50% of initial values and a similar result was noted in response to L-dopa plus carbidopa. In PST and IH patients the prolactin-suppressing effects of L-dopa were comparable to those in normals whereas there was only minimal prolactin suppression by L-dopa plus carbidopa. Normal subjects and patients with PST responded similarly to an influsion of dopamine with a decrease in plasma prolactin levels on the order of 42%. A single dose of bromocriptine suppressed plasma prolactin in normal subjects to 51 +or- 3% of basal values at 2 hours. Patients with PST and IH also exhibited suppression of prolactin values but of lesser magnitude. Patients with PST and IH showed a significantly smaller response to metoclopramide than did normal women. L-dopa administration to postpartum women resulted in greater prolactin suppression than in normal subjects and the suppressive response to L-dopa plus carbidopa wsa less than to L-dopa alone but comparable to that observed in normal subjects. In postpartum subjects alone carbidopa administration for 24 hours resulted in an increase in basal prolactin levels. Prolactin responses to metoclopramide in postpartum subjects was greater than in normal subjects. The suppressive effect of L-dopa was attenuated in patients with CRF. Successful renal transplantation was followed by delayed restoration of the prolactin-suppressing effect of L-dopa. Patients with CRF also had impaired prolactin suppression in response to dopamine and apomorphine and in 2 uremic patients to bromocriptine. The results indicated that alterations in dopaminergic mechanisms vary considerably depending on the etiology of the hyperprolactinemia. The impaired responsiveness cannot be attributed solely to alterations in dopaminergic metabolism secondary to hyperprolactinemia but must be explained at least in part by a separate mechanism.