Decreased dopaminergic control of prolactin secretion in male obesity: normalization by fasting

To test whether short-term fasting has a different effect on hormone release from lactotrophs and thyrotrophs in normal-weight men compared with obese men, 10 mg metoclopramide (MET) was administered orally to seven normal and six obese men before and after a 56-hour fast. In the normal subjects, MET raised the serum prolactin (PRL) level before fasting from 5.1 +/- 1.3 to 58.6 +/- 9.5 micrograms/L in 60 minutes (P less than .02), but left the thyrotropin (TSH) level unaffected. An almost identical hormone response was seen after fasting. Obese men responded differently. Their lactotrophs were initially refractory to MET stimulation (PRL increase from 9.5 +/- 5.1 to 17.5 +/- 5.7 micrograms/L, NS), but became sensitive to such stimulation after fasting (PRL increase from 8.2 +/- 4.5 to 46.3 +/- 6.7 micrograms/L, P less than .01). The thyrotrophs were unaffected by MET before, as well as after, the fast. Although decreased PRL synthesis, reduced cell membrane permeability, and inadequate MET stimulation are plausible mechanisms by which the reduced PRL responsiveness to MET could be explained in the obese patients, neither is likely in view of the fact that the lactotrophs responded promptly to thyrotropin-releasing hormone (TRH), administered intravenously (IV) 60 minutes after MET, in the fed obese patients (PRL increase after TRH from 17.5 +/- 5.7 to a maximum of 48.0 +/- 8.7 micrograms/L, P less than .05). Furthermore, a 50% reduction of the MET dose (5 mg) resulted in a significant PRL response in non-obese healthy men (PRL increase from 3.1 +/- 1.1 to 40.3 +/- 0.9 micrograms/L, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)