Androgen induction of DNA synthesis in the rat penis.

OBJECTIVES

The androgen sensitivity of the mammalian penis has long been appreciated. However, the precise biochemical and structural sequelae of alterations in testosterone, and the mechanisms thereof, remain to be elucidated. Recently, the androgen dependence of rat penile erectile tissue was further clarified at our institution, where the induction of apoptosis was demonstrated in response to castration. In continuity, we report the results of a follow-up study of the regenerative capacity of the regressed, castrated rat penile erectile tissue when testosterone is replenished.

METHODS

Three groups of rats were used: normal control rats, castrated without testosterone replenishment, and castrated with subsequent testosterone replenishment. In the third group, castrated rats were given testosterone and killed at 24-hour intervals over 4 days. Specimens of the penis, small bowel, and prostate were obtained from all animal groups. Immunohistochemical identification of intraperitoneally administered 5-bromo-2'-deoxyuridine, a thymidine analogue, was performed to detect new DNA synthesis. The incorporation of this molecule into high molecular weight nuclear DNA served as a measure of DNA synthesis and, hence, cellular proliferation.

RESULTS

Testosterone-replenished castrated rat penile stromal cells, both cavernosal and spongiosal, showed more enhanced proliferative activity than those of both castrated unreplenished and uncastrated control rats. Trichrome staining permitted the differentiation of responsive cell subsets. Various cell types were found to respond to replenished testosterone, including myocytes, fibrocytes, endothelial cells, and Schwann cells. Pronounced DNA synthesis occurred as early as 48 hours after the replenishment of testosterone. For purposes of technique validation, sections of small bowel were examined, in which glandular crypt cells would be expected to show rapid turnover. The nuclei of these bowel sections stained in all animal groups throughout the experiment, thus validating the staining technique. The technique of castration and testosterone replenishment was validated by confirming the known response of rat ventral prostate to androgen withdrawal and replenishment.

CONCLUSIONS

Our findings provide evidence that testosterone induces cellular proliferation and new DNA synthesis in the penile erectile tissue of castrated rats. This response to testosterone is not limited to one cell type, but rather is multicellular.