Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls
| Autor: | Uberto Pagotto, Federica Tomassoni, Ruth Andrew, Renato Pasquali, Alessandra Gambineri, Flaminia Fanelli, Brian R. Walker, Alessandra Munarini |
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| Přispěvatelé: | Gambineri, Alessandra, Fanelli, Flaminia, Tomassoni, Federica, Munarini, Alessandra, Pagotto, Uberto, Andrew, Ruth, Walker, Brian R., Pasquali, Renato |
| Rok vydání: | 2014 |
| Předmět: |
Adult
endocrine system medicine.medical_specialty Adolescent Hydrocortisone Endocrinology Diabetes and Metabolism Adipose tissue Context (language use) Biology Overweight Excretion Young Adult Endocrinology 11β-hydroxysteroid dehydrogenase type 1 Internal medicine 11-beta-Hydroxysteroid Dehydrogenase Type 1 medicine Humans Obesity General Medicine Middle Aged Polycystic ovary Case-Control Studies biology.protein Female Cortisone medicine.symptom Case-Control Studie hormones hormone substitutes and hormone antagonists Human Polycystic Ovary Syndrome medicine.drug |
| Zdroj: | European Journal of Endocrinology. 171:47-57 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje-13-1030 |
| Popis: | ContextAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic–pituitary–adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.ObjectiveTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.DesignCase–control study.SettingMedical center.PatientsA total of 20 overweight–obese unmedicated Caucasian women with PCOS, aged 18–45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, andHSD11B1genotypes (rs846910 and rs12086634).Main outcome measuresCortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[2H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-2H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity andHSD11B1mRNA were measured,ex vivo, in biopsies.ResultsUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (PHSD11B1mRNA levels and activity were increased (PConclusionsTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS. |
| Databáze: | OpenAIRE |
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