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The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion.

Abstract

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 purpose 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 post AMPT-induced NE depletion mood change in men and/or women. In a randomized, double-blind cross-over fashion, five healthy young males and five females were either given five doses of AMPT 1 g (active) or promethazine 50 mg (placebo) over a 28 h period, separated by 4-6 weeks. The PRL and ML concentrations were collected at regular intervals via an indwelling venous catheter and concurrently, two 12 h urinary 6-hydroxymelatonin sulfate (6-MS) measurements were made. Mood and anxiety states of subjects at baseline and post drug were assessed with appropriate rating scales at regular intervals. Light exposure beginning at dusk and lasting until dawn was controlled to no more than 200 lux during all phases of the study. The PRL secretion showed a significant interaction of drug x time (p = .0001) in women and a non-significant trend (p = .056) in men. No difference in PRL secretion was found between the two genders in the placebo condition, whereas the PRL secretion was significantly higher in the AMPT condition in women when compared to men (df 17,119, F = 1.9, p = .021). Total 24 h urinary 6-MS secretion highly correlated with ML secretion expressed as area under the curve (AUC) during both active and placebo experiments (r = 0.8, p < .01) and (r = 0.86, p < or = .01), respectively. The ANOVA reveals a significant interaction of drug x time for 6-SM excretion. There 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 decrease in CNS NE activity as part of overall AMPT-induced reduction of central catecholamine activities. The pre and post AMPT-induced changes 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.

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  • Authors+Show Affiliations

    ,

    Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA.

    , , , ,

    Source

    Psychoneuroendocrinology 21:5 1996 Jul pg 469-78

    MeSH

    Adult
    Affect
    Arousal
    Cross-Over Studies
    Dopamine
    Double-Blind Method
    Female
    Humans
    Male
    Melatonin
    Methyltyrosines
    Norepinephrine
    Prolactin
    Promethazine
    Reference Values
    Sex Factors
    alpha-Methyltyrosine

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    8888369

    Citation

    Zimmermann, R C., et al. "The Impact of Gender On Alpha-methyl-para-tyrosine Mediated Changes in Prolactin Secretion and 6-hydroxymelatonin Sulfate Excretion." Psychoneuroendocrinology, vol. 21, no. 5, 1996, pp. 469-78.
    Zimmermann RC, Krahn L, Klee G, et al. The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion. Psychoneuroendocrinology. 1996;21(5):469-78.
    Zimmermann, R. C., Krahn, L., Klee, G., Lu, P. Y., Ory, S. J., & Lin, S. C. (1996). The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion. Psychoneuroendocrinology, 21(5), pp. 469-78.
    Zimmermann RC, et al. The Impact of Gender On Alpha-methyl-para-tyrosine Mediated Changes in Prolactin Secretion and 6-hydroxymelatonin Sulfate Excretion. Psychoneuroendocrinology. 1996;21(5):469-78. PubMed PMID: 8888369.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion. AU - Zimmermann,R C, AU - Krahn,L, AU - Klee,G, AU - Lu,P Y, AU - Ory,S J, AU - Lin,S C, PY - 1996/7/1/pubmed PY - 1996/7/1/medline PY - 1996/7/1/entrez SP - 469 EP - 78 JF - Psychoneuroendocrinology JO - Psychoneuroendocrinology VL - 21 IS - 5 N2 - 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 purpose 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 post AMPT-induced NE depletion mood change in men and/or women. In a randomized, double-blind cross-over fashion, five healthy young males and five females were either given five doses of AMPT 1 g (active) or promethazine 50 mg (placebo) over a 28 h period, separated by 4-6 weeks. The PRL and ML concentrations were collected at regular intervals via an indwelling venous catheter and concurrently, two 12 h urinary 6-hydroxymelatonin sulfate (6-MS) measurements were made. Mood and anxiety states of subjects at baseline and post drug were assessed with appropriate rating scales at regular intervals. Light exposure beginning at dusk and lasting until dawn was controlled to no more than 200 lux during all phases of the study. The PRL secretion showed a significant interaction of drug x time (p = .0001) in women and a non-significant trend (p = .056) in men. No difference in PRL secretion was found between the two genders in the placebo condition, whereas the PRL secretion was significantly higher in the AMPT condition in women when compared to men (df 17,119, F = 1.9, p = .021). Total 24 h urinary 6-MS secretion highly correlated with ML secretion expressed as area under the curve (AUC) during both active and placebo experiments (r = 0.8, p < .01) and (r = 0.86, p < or = .01), respectively. The ANOVA reveals a significant interaction of drug x time for 6-SM excretion. There 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 decrease in CNS NE activity as part of overall AMPT-induced reduction of central catecholamine activities. The pre and post AMPT-induced changes 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. SN - 0306-4530 UR - https://www.unboundmedicine.com/medline/citation/8888369/The_impact_of_gender_on_alpha_methyl_para_tyrosine_mediated_changes_in_prolactin_secretion_and_6_hydroxymelatonin_sulfate_excretion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0306-4530(95)00049-6 DB - PRIME DP - Unbound Medicine ER -