Elsevier

Urology

Volume 64, Issue 6, December 2004, Pages 1244-1249
Urology

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

https://doi.org/10.1016/j.urology.2004.06.062Get rights and content

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.

Section snippets

Animals

Male Sprague-Dawley rats aged 6 months (weight range 440 to 560 g) were purchased from Charles River Laboratories (Wilmington, Mass). The rats were divided into three groups. Group 1 (n = 20) served as the nondiabetic control group. In groups 2 (n = 20) and 3 (n = 20), diabetes was induced by two intraperitoneal STZ injections (40 mg/kg) in citrate phosphate buffer (0.1 M citric acid and 0.2 M disodium phosphate, pH 7.0) at a 1-week interval. The development of diabetes was confirmed by blood

Results

The diabetic rats showed significantly lower body weight than the controls. The HbA1 level was high in the diabetic rats but lowered significantly after insulin treatment. The blood glucose levels were significantly greater in the 4-week and 8-week diabetic rats than in the 4-week and 8-week control rats, respectively. The 4-week and 8-week insulin-treated diabetic rats showed statistically significant lower blood glucose levels than did the diabetic rats, respectively.

Comment

We investigated the effect of short-term diabetes and insulin treatment on erectile function using the STZ-induced diabetic rat model, with special reference to the alteration of SHR expression in the smooth muscle cells of the rat crura.

Alterations in ICP and the latency period have been used as in vivo indexes of the impaired neurovascular elements of penile erectile function.14 In this study, a statistically significant reduction in the ICP with a prolonged latency period was observed in the

Conclusions

To our knowledge, this is the first study to demonstrate that insulin treatment may restore erectile function through restoration of SHR gene and protein expression in the diabetic rat crura.

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  • Cited by (0)

    This research was supported by National Institutes of Health grants RO1DK055040 and RO1AG016870.

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