Effects of alcohol on intraovarian nitric oxide synthase and steroidogenic acute regulatory protein in the prepubertal female rhesus monkey

• Published in: Journal of Studies on Alcohol and Drugs Vol. 68; no. 2; pp. 182 - 191
• Main Authors: SRIVASTAVA, Vinod K, DISSEN, Gregory A, OJEDA, Sergio R, HINEY, Jill K, PINE, Michelle D, LES DEES, W
• Format: Journal Article
• Language: English
• Published: Piscataway, NJ Alcohol Research Documentation, Inc., Rutgers, the State University of New Jersey 01-03-2007; Alcohol Research Documentation, Inc
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol and youth; Alcohol consumption; Alcoholism; Alcoholism - physiopathology; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Estradiol - blood; Ethanol - blood; Ethanol - toxicity; Evaluation; Female; Gene Expression - drug effects; Health aspects; Hormones; Juvenile drinking; Luteinizing Hormone - blood; Macaca mulatta; Medical sciences; Menstruation; Monkeys; Nitric Oxide Synthase Type I - genetics; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type III - genetics; Ovary - drug effects; Ovary - physiopathology; Phosphoproteins - genetics; Physiological aspects; Progesterone - blood; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; RNA, Messenger - genetics; Sexual Maturation - drug effects; Toxicology; United States; Human; Ethanol; Enzyme; Alcoholism; Monkey; Steroidogenic acute regulatory protein; Nitric-oxide synthase; Alcoholic beverage; Vertebrata; Toxicology; Mammalia; Prepuberty; Primates; Female; Oxidoreductases
• ISSN: 1937-1888; 1938-4114; 1934-2683
• DOI: 10.15288/jsad.2007.68.182

In addition to affecting hypothalamic-pituitary function, alcohol is a gonadal toxin capable of inhibiting ovarian function and suppressing circulating levels of estradiol (E2) in female rats, rhesus monkeys, and adolescent girls. Both nitric oxide (NO) and steroidogenic acute regulatory protein (StAR) are intraovarian substances that influence steroidogenesis in opposite directions. This study was undertaken to determine whether alcohol exposure affects prepubertal ovarian steroidogenesis in female rhesus monkeys by altering nitric oxide synthase (NOS), StAR, or both.
At 20 months of age, monkeys received a single intragastric dose of alcohol (2.4 g/kg) or an equal volume of a saline/sucrose solution daily until they were 36 months old. Blood and ovaries were then collected for assessment of serum hormone levels and tissue gene and protein expression.
Alcohol caused depressed levels of serum E2 (p < .05) and luteinizing hormone (p < .05) but not follicle-stimulating hormone. Real-time polymerase chain reaction (RT-PCR) assessment of ovarian mRNA encoding the three isoforms (i.e., neuronal [n] NOS, endothelial [e] NOS, and inducible [i] NOS) of NOS revealed that alcohol exposure did not alter gene expression of nNOS but caused increased basal levels of eNOS (p < .05) and iNOS (p < .01) mRNA expression compared with control ovaries. Alcohol also increased expression of eNOS (p < .01) and iNOS (p < .05) proteins. In contrast, ovaries from monkeys exposed to alcohol showed decreased (p < .05) StAR gene expression compared with controls.
We showed previously that alcohol exposure during adolescence suppressed E2 and delayed development of regular monthly menstruation patterns in rhesus monkeys. The present results suggest that the combined action of alcohol to elevate ovarian NOS and suppress StAR synthesis contributes to these abnormalities.