title: Increased 5alpha-reductase and normal 11beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome.
abstract: OBJECTIVE
  To test the hypothesis that 5alpha-reductase (5alphaR) and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity are increased in adolescent and young-adult women with PCOS and that an altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis occurred in these subjects.
  
  
  METHODS
  Prospective non-randomized study in an academic research environment.
  
  
  METHODS
  Eleven women, aged 14 to 25 years, were studied who were at least one year post-menarche and who had a diagnosis of PCOS based on a history of oligomenorrhea and elevated total and or free serum testosterone.
  
  
  METHODS
  24-Hour urinary metabolites were assessed in nine subjects and five underwent stimulation with ovine corticotropin releasing factor (oCRF).
  
  
  METHODS
  C19 and C21 steroid urinary metabolite 5-alpha/5-beta pairs, 11-oxo/11-hydroxy products and the ratio of the total 5-alpha/5-beta reduced and 11-oxo/11-hydroxy products were compared to values in control women. Urinary cortisol (F) (sum of conjugated and free, and free F) and total F metabolites (the sum of THE, THF, 5alpha-THF, cortolones, and cortols) were determined. A 1 microg/kg oCRF stimulation test was performed with timed samples determined for plasma ACTH and serum F levels.
  
  
  RESULTS
  The 24-hour total and free urinary F were not different from control. However, the total F metabolites were markedly elevated (7922+/-2666 vs 5418+/-1549 microg/24 h, p<0.01). A marked increase in the total 5-alpha reduced C19 and C21 metabolites was observed in the PCOS population vs control (5084+/-1977 vs 2681+/-1188 microg/24 h, p<0.01). The total urinary 11-oxo/11-hydroxy metabolite ratio was not different, p=0.23. The basal values and response of both ACTH and F to oCRF stimulation were not different from those of controls.
  
  
  CONCLUSIONS
  There is a marked increase in 5alphaR metabolism of both C19 and C21 steroids in younger women with PCOS.
authors.affiliation: Department of Pediatrics, New York University Medical Center, New York, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chin
authors.forename: C
authors.initials: C
authors.lastname: Shackleton
authors.forename: V K
authors.initials: VK
authors.lastname: Prasad
authors.forename: B
authors.initials: B
authors.lastname: Kohn
authors.forename: R
authors.initials: R
authors.lastname: David
authors.forename: J
authors.initials: J
authors.lastname: Imperato-McGinley
authors.forename: H
authors.initials: H
authors.lastname: Cohen
authors.forename: D J
authors.initials: DJ
authors.lastname: McMahon
authors.forename: S E
authors.initials: SE
authors.lastname: Oberfield
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000201:enzymology*; D011446:Prospective Studies; D013256:Steroids / Q000378:metabolism*
chemical_list: D013256:Steroids; D003346:Corticotropin-Releasing Hormone; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D006854:Hydrocortisone