Endogenous inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 do not explain abnormal cortisol metabolism in polycystic ovary syndrome.
OBJECTIVE
The aetiology of enhanced adrenal androgen secretion in polycystic ovary syndrome is poorly understood. Previous reports suggest that enhanced peripheral metabolism of cortisol results in decreased negative feedback suppression of ACTH secretion, either by enhanced inactivation of cortisol by 5alpha-reductase or impaired reactivation of cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Endogenous inhibitors of hepatic 11beta-HSD1 can be extracted from urine. We have tested the hypothesis that these are increased in patients with polycystic ovary syndrome.


METHODS
A case-control study.


METHODS
57 patients with polycystic ovary syndrome and 27 healthy control women.


METHODS
Aliquots from 24 h urine samples were extracted with Sep-Paks and incubated with rat liver microsomes in which 11beta-HSD1 activity was quantified by conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone.


RESULTS
Inhibition of 11beta-HSD1 activity was not different in extracts from patients compared with controls (40.8 +/- 18.9 arbitrary units in patients vs. 42.7 +/- 16.6 in controls, mean (+/- SEM, P > 0.60) and did not correlate with ratios of cortisol metabolites in urine or with body mass index.


CONCLUSIONS
The altered cortisol metabolism in polycystic ovarian syndrome, which is consistent with impaired 11beta-HSD1 activity, cannot be accounted for by increased production of measurable endogenous inhibitors of this enzyme.
Walker
B R
BR
University of Edinburgh, Endocrinology Unit, Western General Hospital, Edinburgh, UK. B.Walker@ed.ac.uk
Rodin
A
A
Taylor
N F
NF
Clayton
R N
RN
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000293:Adolescent; D000328:Adult; D000818:Animals; D001681:Biological Assay; D016022:Case-Control Studies; D003348:Cortisone / Q000378:metabolism* / Q000652:urine; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000652:urine; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D008862:Microsomes, Liver / Q000201:enzymology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000652:urine; D051381:Rats
D004791:Enzyme Inhibitors; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone