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Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women.

Abstract

Leptin has been called a hormone of reproduction, and seems to link fat and fertility. It has been speculated that the neurotransmitter norepinephrine (NE) (noradrenaline), possibly via the sympathetic nervous system, may represent the afferent signal which modulates leptin release from adipocytes. The purpose of this study was to produce a state of decreased sympathetic output by using the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this compound on the secretion of leptin from fat cells. Ten subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks using a randomized, double-blind, placebo-controlled, cross-over design. Blood samples for hormone measurements were obtained over 24 h (18 time points) on day 2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P < 0.05). Plasma leptin concentrations measured in the control group in women and men were similar to those reported previously in lean subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes with an increase of nocturnal concentrations by approximately 50%. Two-way analysis of variance reveals no significant difference in leptin secretion between the control and active groups in women and men. In summary, preliminary results do not support the hypothesis that NE represents the afferent signal from the central nervous system which modulates leptin release from adipocytes in the human. Further studies are needed to define the role of the sympathetic nervous system as well as NE in the regulation of leptin secretion and its involvement in obesity and reproduction.

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  • Authors+Show Affiliations

    ,

    Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.

    , ,

    Source

    MeSH

    Adult
    Body Weight
    Catecholamines
    Female
    Humans
    Leptin
    Male
    Methoxyhydroxyphenylglycol
    Presynaptic Terminals
    Proteins
    Reference Values
    Sex Characteristics
    Time Factors
    alpha-Methyltyrosine

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    9619531

    Citation

    Zimmermann, R C., et al. "Prolonged Inhibition of Presynaptic Catecholamine Synthesis Does Not Alter Leptin Secretion in Normal-weight Men and Women." Human Reproduction (Oxford, England), vol. 13, no. 4, 1998, pp. 822-5.
    Zimmermann RC, Krahn L, Rahmanie N, et al. Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women. Hum Reprod. 1998;13(4):822-5.
    Zimmermann, R. C., Krahn, L., Rahmanie, N., & Sauer, M. V. (1998). Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women. Human Reproduction (Oxford, England), 13(4), pp. 822-5.
    Zimmermann RC, et al. Prolonged Inhibition of Presynaptic Catecholamine Synthesis Does Not Alter Leptin Secretion in Normal-weight Men and Women. Hum Reprod. 1998;13(4):822-5. PubMed PMID: 9619531.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women. AU - Zimmermann,R C, AU - Krahn,L, AU - Rahmanie,N, AU - Sauer,M V, PY - 1998/6/10/pubmed PY - 1998/6/10/medline PY - 1998/6/10/entrez SP - 822 EP - 5 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 13 IS - 4 N2 - Leptin has been called a hormone of reproduction, and seems to link fat and fertility. It has been speculated that the neurotransmitter norepinephrine (NE) (noradrenaline), possibly via the sympathetic nervous system, may represent the afferent signal which modulates leptin release from adipocytes. The purpose of this study was to produce a state of decreased sympathetic output by using the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this compound on the secretion of leptin from fat cells. Ten subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks using a randomized, double-blind, placebo-controlled, cross-over design. Blood samples for hormone measurements were obtained over 24 h (18 time points) on day 2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P < 0.05). Plasma leptin concentrations measured in the control group in women and men were similar to those reported previously in lean subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes with an increase of nocturnal concentrations by approximately 50%. Two-way analysis of variance reveals no significant difference in leptin secretion between the control and active groups in women and men. In summary, preliminary results do not support the hypothesis that NE represents the afferent signal from the central nervous system which modulates leptin release from adipocytes in the human. Further studies are needed to define the role of the sympathetic nervous system as well as NE in the regulation of leptin secretion and its involvement in obesity and reproduction. SN - 0268-1161 UR - https://www.unboundmedicine.com/medline/citation/9619531/Prolonged_inhibition_of_presynaptic_catecholamine_synthesis_does_not_alter_leptin_secretion_in_normal_weight_men_and_women_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/13.4.822 DB - PRIME DP - Unbound Medicine ER -