Studies on the Role of Natural and Synthetic Sex Steroids in the Regulation of Carbohydrate Metabolism

Abstract

This thesis examines the effects of natural and synthetic sex steroids on the regulation of glucose homeostasis in adult female mice. Natural (estradiol-17B) and synthetic (ethynyl estradiol) estrogens elevate plasma insulin concentrations, glycogen deposition and peripheral glucose utilisation, and reduce plasma glucose concentrations. Natural (progesterone) and synthetic (norethnodrel and norethisterone acetate) progestogens elevate plasma insulin concentrations and glycogen deposition, reduce peripheral glucose utilisation, and frequently elevate plasma glucose concentrations. Since progestogens generally have deleterious effects on glucose homeostasis, their use is contra-indicated in those individuals with compromised B cell status. Natural sex steroids have a greater hypoglycaemic and hyperinsulinaemic influence than synthetic sex steroids. Combined steroid preparations elevate glycogen deposition, increase peripheral glucose utilisation and lower plasma glucose without elevating plasma insulin. Synthetic combined steroid preparations have a greater hypoglycaemic and hyperinsulinaemic influence than natural combined steroid preparations. Combined sex steroid preparations have a beneficial influence on glucose homeostasis and do not appear to represent a diabetic threat in normal healthy individuals. Antagonism between the two steroid components may play a role in improving glucose homeostasis. The subcutaneous route of administration potentiates, whereas the intramuscular and oral routes generally reduce the efficacy of the steroid preparations which benefit glucose homeostasis. Thus, more frequent use of the subcutaneous route might be advantageous in hormonal contraceptive users. The present study shows that female sex steroids influence carbohydrate homeostasis via changes in plasma insulin concentrations. Since these steroids bind to tissues involved in glucose metabolism, including liver, muscle, fat and pancreas, they may also act directly on these tissues. In addition, sex steroids might affect glucose homeostasis via changes in circulating adrenocorticoid levels.