Effects of Chronic Ethanol (EtOH) Administration on Pro-Inflammatory Cytokines of the Hypothalamic-Pituitary-Gonadal (HPG) Axis in Female Rats

Abstract

We and others have investigated the effects of acute and chronic ethanol (EtOH) administration on function of the hypothalamic-pituitary-gonadal (HPG) axis in female rats, consistently finding EtOH to be detrimental. There are now substantial data that pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), have anti-reproductive effects. If EtOH increased levels of these cytokines, such data would be consistent with, though not necessarily prove, a cytokine mediated mechanism for EtOH’s deleterious effects on reproduction. Young adult female Sprague Dawley rats were used. In the experiment reported here, the Lieber DeCarli diet was used, with animals fed a 36% EtOH containing diet or pair fed an identical diet which contained dextrimaltose instead of EtOH. This was done for 4 to 6 weeks. TNFα and IL-6 were measured in the hypothalamus, pituitary, and ovary by ELISA. EtOH exposure resulted in significant increases in TNFα and IL-6 in hypothalami, pituitaries, and ovaries. The data reported here are the first to show consistent stimulatory effects of EtOH exposure on cytokines in the reproductive axis of female rats. Because the effects of these cytokines are generally anti-reproductive, these data provide a rational for more rigorous testing of the notion that part of EtOH’s deleterious HPG effects may be due to such immuno-endocrine interactions.

KeyWords:

• Ethanol
• TNFα
• IL-6
• Hypothalamus
• Pituitary
• Gonad

ACKNOWLEDGMENTS

This work was supported by grants from the Medical Research Service of the Department of Veterans Affairs (Nicholas Emanuele), by NIH AA12034 (Elizabeth J. Kovacs), and by the Ralph and Marion C. Falk Foundation (Elizabeth J. Kovacs).