This work was graciously supported by the National Institutes of Health and the National Institute on Alcohol Abuse and Alcoholism.
Effect of Nitric Oxide Synthase Inhibitors on Preventing Ethanol-Induced Suppression of the Hypothalamic-Pituitary-Gonadal Axis in the Male Rat
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 22, Issue 8, pages 1763–1770, November 1998
How to Cite
Shi, Q., Emanuele, N. V. and Emanuele, M. A. (1998), Effect of Nitric Oxide Synthase Inhibitors on Preventing Ethanol-Induced Suppression of the Hypothalamic-Pituitary-Gonadal Axis in the Male Rat. Alcoholism: Clinical and Experimental Research, 22: 1763–1770. doi: 10.1111/j.1530-0277.1998.tb03977.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication December 22, 1997; accepted August 5, 1998
- Key Words:;
- Nitric Oxide;
Ethanol (EtOH) suppression of the hypothalamic-pituitary-gonadal (HPG) axis results in broad reproductive malfunction. In the HPG axis, the suppressive effects of EtOH are manifested by decreased serum testosterone, reduced testicular luteinizing hormone (LH) receptor numbers, lowered serum LH and pituitary β-LH mRNA levels (in castrated animals), and impaired luteiniring hormone releasing hormone (LHRH) release from the hypothalamus. Increasing evidence has suggested that nitric oxide (NO) plays a role in regulation of the HPG axis. NO was shown to stimulate LHRH secretion from the hypothalamus and to have variable effects on LH release from the pituitary. At the gonadal level, NO is inhibitory to testosterone production. NO may directly inhibit some testicular steroidogenic enzymes. To investigate the effect of EtOH, NO, and their interaction on the male HPG axis, three NO synthase (NOS) inhibitors, NQ-nitro-l-arginine methyl ester, NQ-nitro-l-arginine, and 7-nitro indazole were used to study overall HPG function in the presence and absence of EtOH. Animals were given intraperitoneal injections of saline, EtOH, various NOS inhibitors, or EtOH, along with NOS inhibitors 2 hr before sacrifice. Serum testosterone and LH concentrations, pituiiry βLH mRNA levels, hypothalamic LHRH mRNA levels, and LHRH content were determined. It was found that blocking NOS by these NOS inhibitors prevented EtOH-induced suppression of testosterone and, in some cases, serum LH. However, this was not accompanied by concurrent changes with NOS blockade on LHRH mRNA, hypothalamic pro-LHRH or LHRH content or pituitary LH β mRNA levels. It appears that the protective effect of NOS blockade was largely, although not completely, due to a direct effect at the gonadal level.