Effects of Nitric Oxide Synthase Blockade on the Acute Response of the Reproductive Axis to Ethanol in Pubertal Male Rats

• Published in: Alcoholism, clinical and experimental research Vol. 23; no. 5; pp. 870 - 877
• Main Authors: Emanuele, M. A., LaPaglia, N., Steiner, J., Kirsteins, L., Emanuele, N. V.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1999; Lippincott Williams & Wilkins
• Subjects: Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Drug Antagonism; Enzyme Inhibitors - pharmacology; Ethanol; Ethanol - pharmacology; Leydig Cells - drug effects; Leydig Cells - metabolism; Luteinizing Hormone; Luteinizing Hormone - blood; Luteinizing Hormone Releasing Hormone; Male; Medical sciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Testosterone; Testosterone - blood; Toxicology; Endocrinopathy; Androgen; Ethanol; Rat; Toxicity; Rodentia; Peptide hormone; Gonadotropin RH; Male; Gonadotropin; Gene expression; Glycoprotein hormone; Hypothalamic hormone; Testosterone; Vertebrata; Mammalia; Adenohypophyseal hormone; Nitric oxide; Luteinizing hormone; Testicular hormone; Puberal animal; Hormone releasing factor; Sex steroid hormone; Mechanism of action
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.1999.tb04196.x

The effects of ethanol (EtOH) and nitric oxide (NO) are well known in the adult male rat reproductive axis. In the present study, we investigate the effects of EtOH, NO, and their interaction on key genes and reproductive hormone levels in mid‐(45‐day) and late pubertal(55‐day) male rats. Using three different NO synthase blockers—N‐nitro‐L‐arginine methyl ester (L‐NAME), N;‐nitro‐L‐arginine (L‐NA), and 7‐nitroi‐ndazole—we show that it is possible to block, in part, some of the disruptive effects of EtOH. L‐NAME totally prevented the EtOH‐induced fall in serum testosterone in both 45‐ and 55‐day‐old rats (p < 0.05 and p < 0.001, respectively). On the other hand, the D‐NAME, an inactive isomer of L‐NAME, did not protect testosterone from suppression caused by EtOH. Similarly, L‐NA and 7‐nitroindazole prevented the suppression of testosterone caused by EtOH in 55‐day‐old animals (p < 0.001 L‐NA and p <0.05 for 7‐nitroindazole), but not in the 45‐day‐old rats. Serum luteinizing hormone (LH) was significantly reduced by EtOH in all the studies in both age groups. L.‐NAME (but not D‐NAME) and L‐NA prevented this inhibition in 55‐day‐old animals (p < 0.001 for L‐NAME and p < 0.01 for L‐NA). However, only L‐NA was able to prevent the effects of EtOH on LH in the 45‐day‐old rats. 7‐Nitroindazole was unable to prevent the decrease in LH in either age group. Despite changes in the other reproductive hormones, there were no consistent changes in hypothalamic concentrations of either LH releasing hormone (LHRH) or its precursor. pro‐LHRH. No treatment caused any change in steady‐state levels of β‐LH mRNA. There were no consistent changes in pro‐LHRH mRNA; but, interestingly, in 45‐day‐old rats, L‐NA given with or without EtOH lead to a significant fall in LHRH gene expression. Our findings indicate that the acute suppressive effects of EtOH on the hypothalamic‐pituitary‐gonadal axis of the purbertal male rat can be at least partially prevented by NO synthase blockade.