Androgen control of cyclooxygenase expression in the rat epididymis

Bradykinin and a number of peptide hormones such as angiotensin, endothelin , and vasopressin stimulate anion secretion in rat epididymis via local for mation of PGE(2). These effects are mediated by cyclooxygenase (COX)-1 isoz yme. The present study was undertaken to assess the androgen control of COX expression in the epididymis. Adult male Sprague-Dawley rats were bilatera lly castrated through a scrotal route. Reverse transcription-polymerase cha in reaction was used to measure COX-1 and COX-2 mRNAs in the epididymis in normal and castrated rats. Anion secretion in epithelia grown from the epid idymides of these rats was studied by the short-circuit current technique. In normal rats, COX-1 and COX-2 mRNAs were detected in the intact epididymi s. Elimination of spermatozoa by the technique of efferent duct ligation or flushing out spermatozoa did not affect the expression of either enzyme in the epididymis, indicating that the epithelium, but not spermatozoa, expre ssed the enzymes. Castration caused a time-dependent decrease in expression of COX-1 and COX-2 mRNAs, which were partially restored upon testosterone replacement. In epithelia cultured from castrated rats, there was a complet e loss of bradykinin-induced anion secretion. This effect was reversible up on testosterone replacement. Although epithelia from castrated rats did not respond to bradykinin, they could respond to cAMP, forskolin, and PGE(2) w ith only 20% loss of response magnitude when compared with epithelia from n ormal rats. These results suggest that the expression of COX-1 and COX-2 ar e dependent on androgen. The loss of COX-1 expression after castration corr elates with the specific loss of anion secretion induced by bradykinin and possibly other hormones.