Enhanced prolactin responsiveness to galanin in patients with Cushing's disease.

Abstract

Galanin is believed to play a role in the control of prolactin (PRL) secretion in the rat. Such a role is uncertain in humans where the neuropeptide is expressed by the corticotrophs. However, in clinical conditions of enhanced ACTH secretion, increased PRL levels are often observed. Therefore, we evaluated the effect of galanin infusion on serum PRL levels in patients with Cushing's disease and in control subjects. For comparison, the PRL responses to TRH and metoclopramide were also investigated in the same patients. Four tests were performed: (a) 40-minute infusion of 0.3 micrograms/kg/min of galanin; (b) infusion of normal saline only; (c) metoclopramide test (10 mg as i.v. bolus); (d) TRH test (200 mg as i.v. bolus). Twenty-four normal subjects and nine patients suffering from active Cushing's disease were investigated. Serum concentrations of PRL were measured by radioimmunoassay on blood samples collected before and for 90 minutes after drug or saline administration. Serum baseline PRL levels were superimposable in normal subjects and in patients with Cushing's disease. In normal subjects, infusion of galanin induced a distinct PRL increase compared to saline (mean +/- SEM incremental areas 6514 +/- 2572 vs 540 +/- 571 mU/l/90 min, P = 0.05, respectively). In patients with Cushing's disease, galanin evoked a remarkable PRL rise with hormone levels which were significantly greater (P < 0.001) than those observed in the same patients after infusion of saline (21908 +/- 4180 vs 534 +/- 1556 mU/l/90 min) or after galanin administration in controls (P < 0.01). The PRL response to TRH and, much more so, to metoclopramide was significantly lower in patients with Cushing's disease than in normal subjects (42125 +/- 8000 vs 73181 +/- 7246 mU/l/90 min, P < 0.01 after TRH and 79095 +/- 27265 vs 229049 +/- 10602 mU/l/90 min, P < 0.01 after metoclopramide). Galanin appears to be a specific, though weak, PRL secretagogue in normal subjects. The galanin-induced PRL release was significantly increased in patients with Cushing's disease. A number of hypothetical mechanisms may underlie the enhanced PRL reactivity to galanin in Cushing's disease. This finding together with the impaired PRL responsiveness to TRH and metoclopramide, also observed in this study, is a further example of a dysregulation of PRL secretion in patients with Cushing's disease.