Genetic Variation in 11β-Hydroxysteroid Dehydrogenase Type 1 Predicts Adrenal Hyperandrogenism among Lean Women with Polycystic Ovary Syndrome

2007 ◽  
Vol 2007 ◽  
pp. 391-393
Author(s):  
A.W. Meikle
Keyword(s):  
Genetic Variation ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
Ovary Syndrome ◽  
Adrenal Hyperandrogenism

scholarly journals Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

2014 ◽  
Vol 171 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Alessandra Gambineri ◽  
Flaminia Fanelli ◽  
Federica Tomassoni ◽  
Alessandra Munarini ◽  
Uberto Pagotto ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
Whole Body ◽  
Mrna Levels ◽  
Ovary Syndrome ◽  
Tissue Specific ◽  
Cortisol Metabolism ◽  
Cortisol Metabolites

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 (P<0.05), whereas subcutaneous abdominal adipose tissueHSD11B1mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.ConclusionsTissue-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.

scholarly journals Cortisol-Metabolizing Enzymes in Polycystic Ovary Syndrome

2016 ◽  
Vol 10 ◽  
pp. CMRH.S35567 ◽  
Author(s):  
Zeev Blumenfeld ◽  
Gabi Kaidar ◽  
Nehama Zuckerman-Levin ◽  
Elena Dumin ◽  
Carlos Knopf ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Young Women ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
The Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Ovary Syndrome ◽  
Metabolizing Enzymes

Objective The aim of this study was to assess the activity of cortisol-metabolizing enzymes in women with polycystic ovary syndrome (PCOS), using a fully quantitative gas chromatography/mass spectrometry (GCMS) method. Design We investigated the glucocorticoid degradation pathways that include llβ-hydroxysteroid dehydrogenase (llβ-HSD) type 1, 5α-reductase (5α-R) and 5β-reductase (5β-R), 3α-hydroxysteroid dehydrogenase, and 20α- and 20β-hydroxysteroid dehydrogenase (20α-HSD and 20β-HSD, respectively) in young nonobese women with PCOS, using a fully quantitative GCMS method. Setting This study was conducted in a tertiary referral hospital in Israel. Patients This study group consisted of 13 young women, aged 20.1 ±2.8 years (mean ± SD), with the body mass index (BMI) of 22.6 ± 3.7 kg/m2, diagnosed with PCOS according to the Rotterdam criteria. The control group consisted of 14 healthy young women matched for weight, height, and BMI. Interventions Urine samples were analyzed using GCMS. We measured urinary steroid metabolites that represent the products and substrates of the study enzymes and calculated the product/substrate ratios to represent enzyme activity. Main Outcome Measures The calculation of enzymatic activity, based on glucocorticoid degradation metabolites, was done by GCMS in PCOS vs. controls. Results All glucocorticoid degradation metabolites were higher in the PCOS group than in controls. Of the adrenal enzymes, the activities of 21-hydroxylase and 17α-hydroxylase were reduced, whereas the activity of 17,20-lyase was enhanced in PCOS. Of the degradation enzymes, the activity of 11β-HSD type 1 was reduced in women with PCOS only when calculated from cortoles and cortolones ratios. The activities of 5α-R/5β-R were increased only when calculating the 11-hydroxy metabolites of androgens. The activity of 20α-HSD was elevated in the patients with PCOS and its relation with the substrate levels was lost. Conclusions We confirm PCOS association with low 21-hydroxylase activity. PCOS is associated with dysregulation in glucocorticoid degradation. The activity of 5α-R is enhanced only through the backdoor pathway. Marked increase in the activity of 20α-HSD suggests a hitherto unknown derangement in PCOS.

scholarly journals A Study of the Hexose-6-Phosphate Dehydrogenase Gene R453Q and 11β-Hydroxysteroid Dehydrogenase Type 1 Gene 83557insA Polymorphisms in the Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (7) ◽  
pp. 4157-4162 ◽  
Author(s):  
José L. San Millán ◽  
José I. Botella-Carretero ◽  
Francisco Álvarez-Blasco ◽  
Manuel Luque-Ramírez ◽  
José Sancho ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
Ovary Syndrome ◽  
Dehydrogenase Gene

Phenotypic characteristic of type 1 diabetic women with polycystic ovary syndrome

2015 ◽  
Author(s):  
Agnieszka Lebkowska ◽  
Agnieszka Adamska ◽  
Monika Karczewska-Kupczewska ◽  
Agnieszka Nikolajuk ◽  
Elzbieta Otziomek ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Phenotypic Characteristic ◽  
Ovary Syndrome

Adrenal Hyperandrogenism and Polycystic Ovary Syndrome

2016 ◽  
Vol 22 (36) ◽  
pp. 5588-5602 ◽  
Author(s):  
Manuel Luque-Ramírez ◽  
Héctor Escobar-Morreale
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Adrenal Hyperandrogenism
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