The Effect of Neonatal Sex Hormone Manipulation on the Incidence of Diabetes in Nonobese Diabetic Mice

Abstract

The nonobese diabetic (NOD) mouse is a model of Type I (insulin-dependent) diabetes. It develops autoimmune pancreatic β-cell lesions characterized by lymphocytic infiltration and β-cell destruction. The incidences of diabetes for male and female NOD mice in our colony were 24% and 73%, respectively. In this study, we investigated the effect of neonatal manipulation of the sex hormone profile on the incidence of diabetes in male and female NOD mice. One day after birth, male mice were castrated and female mice were either ovariectomized, given testosterone, or ovariectomized and given testosterone. The mice were maintained for 140 days and blood samples were collected biweekly starting at 42 days old. Diabetes was determined by three consecutive blood glucose levels > 200 mg/dl. Neonatal gonadectomy increased the incidence of diabetes in males but decreased it in females. Females treated with testosterone also had a decreased incidence of diabetes, whereas ovariectomy plus testosterone increased the incidence to 100%. Castration decreased the body weight in males and increased body weight in females. Testosterone treatment with or without ovariectomy also increased body weight. From these studies, we concluded that neonatal hormonal imprinting has a significant influence on the incidence of diabetes in the NOD mouse.