Endocrine Abstracts

Cortisol is metabolised by two 11βHSD isoenzymes. Recently, we reported that 11βHSD1 and 11βHSD2 mRNA and protein are co-expressed in boar testis and throughout the male reproductive tract. However, enzyme activities were only detectable in boar testis, caput epididymidis, bulbourethral glands and penile urethra. The objective of the present study was to assess whether cortisol–cortisone metabolism in the boar testis and caput epididymidis could be regulated via the gonadotrophin-cAMP signalling pathway, androgens and their 7/11-oxysteroid metabolites. 11βHSD activities were measured using a radiometric conversion assay. Freshly isolated pieces of boar testis and caput epididymidis (1 cm³) were incubated for 2 h in 1 ml phosphate-buffered saline containing either 100 nmol/l [1,2,6,7-³H]-cortisol or [1,2,(n)-³H]-cortisone ±1 μg/ml LH, 1 μg/ml FSH, forskolin, 8-br-cAMP, testosterone (T), 11αOH-T, 11βOH-T, 11-keto-T, DHEA, 7αOH-DHEA, 7βOH-DHEA, or 7-keto-DHEA (each at a concentration of 10 μmol/l). In testis, net 11-ketosteroid reductase (11KSR) activity, but not 11β-dehydrogenase activity, was significantly inhibited by forskolin, 8-br-cAMP and LH (by 59.7±7.0%, 54.0±4.3% and 53.0±20.1% respectively, P<0.05). H89 partially reversed the inhibitory effects of forskolin on 11KSR activity. In caput epididymidis, net 11KSR (but not 11β-dehydrogenase) activity was significantly inhibited by forskolin, 8-br-cAMP, LH and FSH (by 56.6±9%, 64.4±1.1%, 45.0±9.1% and 54.4±8.8% respectively, P<0.05). In boar testis, 11βDH activity was significantly inhibited by T, 11αOH-T, 11βOH-T and 11-keto-T (by 34.8±4.5%, 71.3±9.4%, 83.5±4.6% and 76.5±2.6% respectively, P<0.05). In caput epididymidis, 11β-dehydrogenase activity was significantly inhibited by 11αOH-T, 11βOH-T and 11-keto-T (by 55.4±13.6%, 77.2±3.6% and 72.3±6.0% respectively, P<0.05) but not T itself. DHEA and its 7-oxy derivatives exerted no significant effect on cortisol–cortisone metabolism in either tissue. Gonadotrophin-cAMP signalling pathways, testosterone and its 11-oxy-metabolites regulate 11βHSD enzyme activities which may influence the local actions of glucocorticoids in boar testis and/or epididymis.