Androgen, estrogen, and progesterone receptor gene regulation during diabetic erectile dysfunction and insulin treatment

Abstract

Objectives To determine whether altered levels of sex hormone receptor genes (androgen, estrogen, and progesterone receptors) are involved in the etiology of diabetes-related erectile dysfunction. Insulin treatment can restore erectile function through modulation of sex hormone receptor genes. Methods Diabetes was induced in rats (n = 40) by intraperitoneal injection of streptozotocin. The diabetic rats were divided into two groups: untreated rats (n = 20) and rats treated daily with 10 U subcutaneous human recombinant insulin (n = 20). Control nondiabetic rats (n = 20) were given only vehicle. Erectile function was analyzed by measurement of intracavernous pressure. Gene and protein expression of sex hormone receptors were analyzed by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Results The mean intracavernous pressure was significantly decreased in the diabetic rats compared with the controls and was restored to normal after insulin treatment. In the diabetic rat crura, mRNA and protein expression for estrogen receptor-β and progesterone receptor were significantly lower than in the control crura, and the expression profile of androgen receptor and estrogen receptor-β did not change. Insulin treatment restored estrogen receptor-β and progesterone receptor mRNA and protein expression. Insulin treatment significantly increased the expression of mRNA and protein for androgen receptor and estrogen receptor-α in diabetic rats compared with control rats. Conclusions This is the first study to demonstrate that insulin treatment may restore erectile function through restoration of sex hormone receptor gene and protein expression in the diabetic rat crura.