Increased 5alpha-reductase and normal 11beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome.
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.
Chin
D
D
Department of Pediatrics, New York University Medical Center, New York, USA.
Shackleton
C
C
Prasad
V K
VK
Kohn
B
B
David
R
R
Imperato-McGinley
J
J
Cohen
H
H
McMahon
D J
DJ
Oberfield
S E
SE
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*
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