title: Ovarian 11β-hydroxysteroid dehydrogenase (11βHSD) activity is suppressed in women with anovulatory polycystic ovary syndrome (PCOS): apparent role for ovarian androgens.
abstract: BACKGROUND
  Altered hepatic cortisol-cortisone metabolism by type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) has previously been linked with polycystic ovary (PCO) syndrome (PCOS).
  
  
  OBJECTIVE
  Our objectives were to establish whether ovarian 11βHSD activities are also altered in PCOS and to determine whether any changes in ovarian cortisol metabolism might reflect exposure to elevated concentrations of insulin or androgens.
  
  
  METHODS
  Cortisol and cortisone concentrations were measured in follicular fluid aspirated from size-matched follicles dissected from normal, ovulatory, and anovulatory PCOs. Human granulosa-lutein cells, recovered during oocyte retrieval for assisted conception, were maintained in primary culture for 4 days, after which 11βHSD1 activities were measured as the net oxidation of [(3)H]cortisol (100 nmol/L) in the absence and presence of insulin (100 nmol/L) with or without metformin (1 μmol/L) or a range of androgens/oxy-androgen metabolites (0.01-10 μmol/L).
  
  
  RESULTS
  Intrafollicular cortisol to cortisone ratios were elevated in anovulatory PCOs (2.1 ± 0.4, P < .05, n = 13) but did not differ between follicles from ovulatory PCOs (1.6 ± 0.1, n = 24) and normal ovaries (1.2 ± 0.1, n = 14). 11βHSD1 activities were lower in granulosa-lutein cells recovered from patients with PCOS compared with all other causes of infertility (median = 5.8 vs 14.9 pmol cortisone/4 h, respectively; P < .05). Cortisol oxidation was unaffected by insulin with or without metformin, dehydroepiandrosterone, and androstenedione, but was inhibited in a concentration-dependent manner by testosterone, 11β-hydroxyandrostenedione, and 7α- and 7β-hydroxy-dehydroepiandrosterone (P < .01).
  
  
  CONCLUSIONS
  There is decreased inactivation of cortisol in follicles from anovulatory PCOS. This may reflect inhibition of 11βHSD1 by androgens and their 7/11-oxy-metabolites, local concentrations of which are increased in PCOS, and may contribute to the block to folliculogenesis seen in PCOS.
authors.affiliation: Division of Biomedical Sciences, Room J2.140B, Jenner Wing, St. George's (University of London), Cranmer Terrace, London SW17 0RE, United Kingdom. aemichae@sgul.ac.uk
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Michael
authors.forename: Christine
authors.initials: C
authors.lastname: Glenn
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wood
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Webb
authors.forename: Laura
authors.initials: L
authors.lastname: Pellatt
authors.forename: Helen D
authors.initials: HD
authors.lastname: Mason
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000328:Adult; D000728:Androgens / Q000494:pharmacology*; D000858:Anovulation / Q000378:metabolism*; D003348:Cortisone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007247:Infertility, Female / Q000209:etiology; D007328:Insulin / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D008875:Middle Aged; D010053:Ovary / Q000201:enzymology*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*
chemical_list: D000728:Androgens; D007328:Insulin; D008687:Metformin; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone