A Study of the Effects of Ovariectomy and Ovarian Hormone Replacement Therapy on Carbohydrate Metabolism in Mice

Abstract

This thesis examines the effects of long-term ovariectomy and ovarian hormone replacement therapy on the regulation of glucose homeostasis and certain aspects of lipid metabolism in adult female mice. Long-term (15 weeks) ovariectomy increased body weight, food intake and intestinal glucose absorption. This was accompanied by increased gluconeogenesis and reduced glycogenesis in the liver, skeletal muscle, heart and uterus. Glucose tolerance was impaired and the insulin response to glucose, arginine, glucagon and epinephrine was reduced. Insulin sensitivity was decreased, and the antagonism of insulin by growth hormone and cortisone was more severe. Insulin secretion in vitro was decreased, the total pancreatic and islet insulin content was reduced, and preliminary histological studies showed evidence of a reduction in β-cell numbers and some islet degeneration. Plasma non-esterified fatty acids, triglycerides and cholesterol levels were increased. Oestradiol, progesterone and a combination of these hormones reversed the effects of ovariectomy, and returned most values to within the range of normal intact control mice. The mechanisms through which ovarian steroids may produce their effects on carbohydrate and lipid metabolism are discussed. It is tentatively suggested that natural long-term ovarian hormone replacement therapy exerts a beneficial effect on glucose homeostasis in cases of ovarian endocrine insufficiency.