Androgenic action of dehydroepiandrosterone (DHEA) on nerve density in the ovariectomized rat vagina.

Introduction. We have recently reported that dehydroepiandrosterone (DHEA) increases the density of nerve fibers in the ovariectomized (OVX) rat vagina. Aim. To better define the mechanism of action of DHEA, we have examined the effect of DHEA, conjugated estrogens (premarin) and the potent blocker of estrogen action acolbifene on the innervation in the lamina propria in the OVX rat vagina. Methods. Female Sprague-Dawley rats (10-12 weeks old) were used. Innervation of the vagina was examined 9 months after OVX and was compared to that of OVX animals treated daily with DHEA (80 mg/kg) by topical application on the skin, premarin (0.5 mg/kg) orally as well as acolbifene (2.5 mg/kg) orally administrated alone or in combination with DHEA or premarin. Main Outcome Measures. Four histological sections from each vagina (5 animals/group) were immunostained using antibodies to the panneuronal marker protein gene product 9.5 (PGP 9.5). The areas were measured by stereological analysis. Results. OVX reduced the area of the lamina propria to 44% of the intact value, an effect which was reversed to 69% and 84% of the intact value by DHEA and premarin, respectively, at the doses used. When acolbifene was used, no inhibition of the stimulatory effect of DHEA was observed, while the action of premarin was completely blocked. Evaluation of the PGP 9.5 fiber density revealed that DHEA treatment increased the density of fibers by 60% compared to OVX animals, while a further 27% increase was observed when acolbifene was combined with DHEA. Premarin, on the other hand, had no effect on the density of PGP 9.5 fibers. Conclusions. Considering that the antiestrogen acolbifene had no inhibitory effect on the effect of DHEA in rat vagina while blocking the stimulatory effect of premarin, the present data indicate that DHEA exerts its stimulatory effect on the fiber density through an androgenic action.