Interaction of Ethanol and Nitric Oxide in the Hypothalamic-Pituitary-Gonadal Axis in the Male Rat

Authors

  • Qin Shi,

    1. Departments of Molecular and Cellular Biochemishy (Q.S., M.A.E.) and Medicine (N.KE., MAE.), the Molecular Biology Program (N.KE., M.A.E.), the Division of Research on Drugs of Abuse of the Neuroscience and Aging Institute (Q.S., N.V.E., M.A.E.), Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois; Research and Medical Services (N.V.E., M.A.E.), Veterans Affairs Hospital, Hines, Illinois; and the Department of Physiology and Biophysics (D.B.H., N. KE., MAE.), College of Medicine, University of Illinois at Chicago, Chicago, Illinok.
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  • Dale B. Hales,

    1. Departments of Molecular and Cellular Biochemishy (Q.S., M.A.E.) and Medicine (N.KE., MAE.), the Molecular Biology Program (N.KE., M.A.E.), the Division of Research on Drugs of Abuse of the Neuroscience and Aging Institute (Q.S., N.V.E., M.A.E.), Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois; Research and Medical Services (N.V.E., M.A.E.), Veterans Affairs Hospital, Hines, Illinois; and the Department of Physiology and Biophysics (D.B.H., N. KE., MAE.), College of Medicine, University of Illinois at Chicago, Chicago, Illinok.
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  • Nicholas V. Emanuele,

    1. Departments of Molecular and Cellular Biochemishy (Q.S., M.A.E.) and Medicine (N.KE., MAE.), the Molecular Biology Program (N.KE., M.A.E.), the Division of Research on Drugs of Abuse of the Neuroscience and Aging Institute (Q.S., N.V.E., M.A.E.), Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois; Research and Medical Services (N.V.E., M.A.E.), Veterans Affairs Hospital, Hines, Illinois; and the Department of Physiology and Biophysics (D.B.H., N. KE., MAE.), College of Medicine, University of Illinois at Chicago, Chicago, Illinok.
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  • Mary Ann Emanuele

    Corresponding author
    1. Departments of Molecular and Cellular Biochemishy (Q.S., M.A.E.) and Medicine (N.KE., MAE.), the Molecular Biology Program (N.KE., M.A.E.), the Division of Research on Drugs of Abuse of the Neuroscience and Aging Institute (Q.S., N.V.E., M.A.E.), Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois; Research and Medical Services (N.V.E., M.A.E.), Veterans Affairs Hospital, Hines, Illinois; and the Department of Physiology and Biophysics (D.B.H., N. KE., MAE.), College of Medicine, University of Illinois at Chicago, Chicago, Illinok.
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  • This work was supported by the National Institutes of Health and the National Institute on Alcohol Abuse and Alcoholism.

Reprint requests: Mary Ann Emanuele, M.D., Department of Medicine, Division of Endocrinology and Metabolism, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153.

Abstract

Ethanol (EtOH) exerts deleterious actions on reproductive function at all three levels: the hypothalamus, pituitary, and gonad (HPG). Nitric oxide (NO), a newly identified messenger molecular in a variety of biological systems, has been suggested as playing a role in HPG hormone regulation. NO stimulates luteinizing hormone releasing hormone secretion from the hypothalamus and has variable effects on luteinizing hormone release from the pituitary. NO is inhibitory to testosterone production, and it may also directly inhibit some steroidogenic enzymes. Related studies in the accompanying paper have demonstrated that inhibiting NO synthase (NOS) using various NOS inhibitors can prevent the EtOH-induced suppression of testosterone on the male HPG axis, and this action is mainly, although not entirely, due to a direct gonadal effect. To further investigate the role of NO in the HPG axis, we assessed the HPG NO-NOS system by determining NOS mRNA levels, protein levels, and enzyme activity in the presence and absence of EtOH. At the testicular level, EtOH's action did not appear to be mediated by increasing NO content. However, EtOH was able to potentiate NO'S suppressive effect on the testicular synthesis system. One locus where EtOH and NO interacted was at the steroidogenic enzyme level. NQ-nitro-l-arginine methyl ester, a NOS inhibitor, was found to antagonize the EtOH-induced fall on P-450 17α-hydroxylase/C17-20 lyase mRNA levels when administered along with EtOH. EtOH had no apparent effect on the pituitary NO-NOS system and its effects on the hypothalamic NO-NOS system do not explain its ability to reduce luteinizing hormone releasing hormone secretion.

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