Effect of food restriction (undernutrition) on plasma sex hormone binding globulin (SHBG) capacity, liver drug metabolizing enzymes and uterine cytosol progesterone receptor levels in rabbits

Abstract

The present investigation was designed to understand the mechanism underlying the altered pharmacokinetic and pharmacodynamic properties of norethindrone and levonorgestrel observed in undernourished rabbits. Eighteen albino rabbits aged 3–4 months were divided into two groups. One group received a stock diet ad libitum and the other group was individually fed half the food consumed by the matched animal in ad lib group. Three pairs of animals were sacrificed at the end of three months and the remaining at the end of five months. Liver and uterine tissues were dissected out and processed for analysis. For both sets of animals, whether killed at the end of three months or 5 months, the trend of results obtained were similar. The capacity and affinity characteristics of plasma sex hormone binding globulin were found to be not significantly different between control and experimental animals. The specific activities of liver microsomal glucuronyl transferase and cytochrome P-450 were significantly higher in undernourished rabbits. The increase observed in the activity of sulfuryl transferase was, however, not statistically significant. Uterine cytosol progesterone receptor levels were found to be higher in food restricted animals though there were no changes in the affinity properties of the receptors. Thus, it appears that imposition of food restriction leads to increased drug metabolism as a result of increased drug metabolizing enzyme activities and that the animals appear to adapt by enhanced target organ response in terms of elevated receptor concentration.