Increased expression of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage and P450 17alpha-hydroxylase enzymes in ovarian hyperthecosis.
OBJECTIVE
To investigate whether the increased ovarian androgen synthesis in hyperthecosis is due to increased expression of the steroidogenic enzymes essential for androgen synthesis.


METHODS
Controlled study to investigate concentration of steroidogenic enzymes in the ovarian stroma of women with hyperthecosis of the ovaries.


METHODS
Academic research environment.


METHODS
Three women with ovarian hyperthecosis and eight with normal ovulatory cycles.


METHODS
Ovarian stromal tissues were obtained from women with hyperthecosis and women with normal ovaries. Diagnosis of hyperthecosis was confirmed by histologic examination of the ovaries. Steroid levels were measured in the ovarian vein serum of one patient with hyperthecosis.


METHODS
Tissues were frozen immediately in liquid nitrogen and kept frozen until RNA was extracted. Total RNA was examined by Northern blot analysis using 32P-labeled complementary DNA (cDNA) probes encoding human P450scc and P450(17alpha) enzymes.


RESULTS
P450scc and P450(17alpha) messenger RNAs (mRNAs) were detected in the normal ovarian stroma and stromal hyperthecosis. Compared with normal ovarian stroma, P450scc mRNA was increased twofold and P450(17alpha) mRNA was increased threefold in stromal hyperthecosis.


CONCLUSIONS
[1] Ovarian stroma is probably the site of androgen production in ovarian hyperthecosis. [2] Increased stromal androgen synthesis in hyperthecosis could be due to increased expression of the enzymes P450scc and P450(17alpha) in the ovarian stroma. [3] Markedly increased concentrations of 17alpha-hydroxyprogesterone in the ovarian vein serum indicate possible dysregulation of P450(17alpha) in ovarian hyperthecosis.
Nagamani
M
M
Division of Reproductive Endocrinology, University of Texas Medical Branch at Galveston, 77555-0587, USA. mnagaman@utmb.edu
Urban
R J
RJ
D000328:Adult; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D005260:Female; D005815:Genetic Code; D006801:Humans; D010049:Ovarian Diseases / Q000473:pathology* / Q000601:surgery; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D017154:Stromal Cells / Q000473:pathology; D013577:Syndrome; D013799:Theca Cells / Q000473:pathology*