THE IMPACT OF GENDER ON ALPHA-METHYL-PARATYROSINE MEDIATED CHANGES INPROLACTIN SECRETION AND 6-HYDROXYMELATONIN SULFATE EXCRETION

Prolactin (PRL) and melatonin (ML) secretion are mediated by dopamine (DA) and norepinephrine (NE), respectively. Alpha-methyl-para-tyrosine (AMPT) inhibits the production, of CNS catecholamines (CA). The purpo se of the study is to determine: (1) if AMPT inhibition of ML has the same gender-dependent effect as on PRL secretion; (2) if there is a po st AMPT-induced NE depletion mood change in men and/or women. In a ran domized double-blind cross-over fashion, live healthy young males and five females were either given five doses of AMPT 1 g (active) or prom ethazine 50 mg (placebo) over a 28 h period, separated by 4-6 weeks. T he PRL and ML concentrations were collected at regular intervals via a n indwelling venous catheter and concurrently, two 12 h urinary 6-hydr oxymelatonin sulfate (6-MS) measurements were made. Mood and anxiety s tates of subjects at baseline and post drug were assessed with appropr iate rating scales at regular intervals. Light exposure beginning at d usk and lasting until dawn was controlled to no more than 200 lux duri ng all phases of the study. The PRL secretion showed a significant int eraction of drug x time (p = .0001) in women and a non-significant tre nd (p = .056) in men. No difference in PRL secretion was found between the two genders in the placebo condition, whereas the PRL secretion w as significantly higher in the AMPT condition in women when compared t o men (df 17,119, F = 1.9, p = .021). Total 24 h urinary S-MS secretio n highly correlated with ML secretion expressed as area under the curv e (AUG) during both active and placebo experiments (r = 0.8, p < .01) and (r = 0.86, p less than or equal to .01), respectively. The ANOVA r eveals a significant interaction of drug x time for 6-SM excretion. Th ere was no gender difference in AMPT suppression of 6-MS excretion. No mood changes were detected in men or women. We conclude that urinary 6-MS is a reliable indirect measure of the degree of AMPT-induced decr ease in CNS NE activity as part of the overall AMPT-induced reduction of central catecholamine activities. The pre and post AMPT-induced cha nges in 6-MS are not gender dependent, dissimilar to the AMPT-induced changes in PRL secretion. Therefore, 6-MS, in addition to PRL, should be measured when applying the AMPT paradigm in future research. Copyri ght (C) 1996 Published by Elsevier Science Ltd