Abstract
The net interconversion of inactive cortisone to active cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11betaHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post-menopausal, oestrogen-deficient women and elderly men. Fifteen healthy men, aged 60.8-82.0 years, and 7 healthy women, aged 62.4-87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post-menopausal and none was receiving sex steroid replacement therapy. 24-h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X-ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF-I and IGFBP1 levels. The ratio of 11-hydroxy cortisol metabolites to 11-oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55-1.86) vs. 0.67 (0.46-0.98) (P < 0.02), as was the ratio of allo-tetrahydrocortisol (5alpha-THF) + tetrahydrocortisol (THF)/tetrahydrocortisone (THE), 0.74 (0.37-2.08) vs. 0.40 (0.22-1.10) (P < 0.047). In the group as a whole there was a negative correlation between Fm/Em and percent body fat, r = - 0. 43 (P < 0.05), and the negative relationship between cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = - 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = - 0.48, and Fm/Em and trunk fat mass, r = - 0.48 which approached significance (both P = 0.07). Serum IGFBP-1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP-1 and Fm/Em in the men, r = 0. 84 (P < 0.0001) which persisted when total body fat mass, r = 0.85 (P < 0.0001) and trunk fat mass, r = 0.83 (P < 0.0001), were controlled for. This relationship was not evident among the women. This study demonstrates that the previously described sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11beta-HSD1 gene expression during the pre-menopausal period cannot be excluded. The findings confirm the primary importance of body fat as a determinant of cortisol-cortisone conversion.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.