11β-hydroxysteroid dehydrogenase enzymes in the testis and male reproductive tract of the boar (Sus scrofa domestica) indicate local roles for glucocorticoids in male reproductive physiology

Abstract

11β-Hydroxysteroid dehydrogenase (11 βHSD) enzymes modulate the target cell actions of corticosteroids by catalysing metabolism of the physiological glucocorticoid (GC), cortisol, to inert cortisone. Recent studies have implicated GCs in boar sperm apoptosis. Hence, the objective of this study was to characterise 11βHSD enzyme expression and activities in the boar testis and reproductive tract. Although 11 βHSD1 and 11βHSD2 mRNA transcripts and proteins were co-expressed in all tissues, cortisol-cortisone interconversion was undetectable in the corpus and cauda epididymides, vas deferens, vesicular and prostate glands, irrespective of nucleotide cofactors. In contrast, homogenates of boar testis, caput epididymidis and bulbourethral gland all displayed pronounced 11 βHSD activities in the presence of NADPH/NADP+, and NAD+, and the penile urethra exhibited NAD+-dependent 11β-dehydrogenase activity. In kinetic studies, homogenates of boar testis, caput epididymidis and bulbourethral gland oxidised cortisol with Km values of 237-443 and 154-226 nmol/l in the presence of NADP+ and NAD+ respectively. Maximal rates of NADP+-dependent cortisol oxidation were 7.4- to 28.5-fold greater than the Vmax for NADPH-dependent reduction of cortisone, but were comparable with the rates of NAD+-dependent cortisol metabolism. The relatively low Km estimates for NADP+-dependent cortisol oxidation suggest that either the affinity of 11βHSD1 has been increased or the cortisol inactivation is catalysed by a novel NADP+ -dependent 11βHSD enzyme in these tissues. We conclude that in the boar testis, caput epididymidis and bulbourethral gland, NADP+- and NAD+-dependent 11βHSD enzymes catalyse net inactivation of cortisol, consistent with a physiological role in limiting any local actions of GCs within these reproductive tissues. © 2007 Society for Reproduction and Fertility.