Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85468
Title:
Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.
Authors:
Toogood, Andy; Taylor, N F; Shalet, Stephen M; Monson, J P
Abstract:
OBJECTIVE: 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. PATIENTS: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.
Affiliation:
Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent. 2000, 52 (1):61-6 Clin. Endocrinol.
Journal:
Clinical Endocrinology
Issue Date:
Jan-2000
URI:
http://hdl.handle.net/10541/85468
DOI:
10.1046/j.1365-2265.2000.00874.x
PubMed ID:
10651754
Type:
Article
Language:
en
ISSN:
0300-0664
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorToogood, Andyen
dc.contributor.authorTaylor, N Fen
dc.contributor.authorShalet, Stephen Men
dc.contributor.authorMonson, J Pen
dc.date.accessioned2009-11-05T17:17:24Z-
dc.date.available2009-11-05T17:17:24Z-
dc.date.issued2000-01-
dc.identifier.citationSexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent. 2000, 52 (1):61-6 Clin. Endocrinol.en
dc.identifier.issn0300-0664-
dc.identifier.pmid10651754-
dc.identifier.doi10.1046/j.1365-2265.2000.00874.x-
dc.identifier.urihttp://hdl.handle.net/10541/85468-
dc.description.abstractOBJECTIVE: 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. PATIENTS: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.en
dc.language.isoenen
dc.subjectOestrogenen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshBody Composition-
dc.subject.meshCortisone-
dc.subject.meshEstrogens-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshHydrocortisone-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 1-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshSex Characteristics-
dc.subject.meshTetrahydrocortisol-
dc.titleSexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalClinical Endocrinologyen
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