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Androgen Control of Cyclooxygenase Expression in the Rat Epididymis¹

^a Department of Physiology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong

ABSTRACT

Bradykinin and a number of peptide hormones such as angiotensin, endothelin, and vasopressin stimulate anion secretion in rat epididymis via local formation of PGE₂. These effects are mediated by cyclooxygenase (COX)-1 isozyme. The present study was undertaken to assess the androgen control of COX expression in the epididymis. Adult male Sprague-Dawley rats were bilaterally castrated through a scrotal route. Reverse transcription-polymerase chain 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 epididymides 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 epididymis. 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, expressed 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 complete loss of bradykinin-induced anion secretion. This effect was reversible upon testosterone replacement. Although epithelia from castrated rats did not respond to bradykinin, they could respond to cAMP, forskolin, and PGE₂ with only 20% loss of response magnitude when compared with epithelia from normal rats. These results suggest that the expression of COX-1 and COX-2 are dependent on androgen. The loss of COX-1 expression after castration correlates with the specific loss of anion secretion induced by bradykinin and possibly other hormones.

FOOTNOTES

First decision: 29 March 2000.

¹ This work was supported by the Research Grant Council (earmarked research grant CUHK4293/99M), the International Consortium on Male Contraception, and the Chinese University of Hong Kong.

² Correspondence. FAX: 852 2603 5022;patrickwong{at}cuhk.edu.hk

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