Estrogen metabolizing enzymes in endometrium and endometriosis.
BACKGROUND
Estradiol (E(2)) is an important promoter of the growth of both eutopic and ectopic endometrium. The findings with regard to the expression and activity of steroidogenic enzymes in endometrium of controls, in endometrium of endometriosis patients and in endometriotic lesions are not consistent.


METHODS
In this study, we have looked at the mRNA expression and protein levels of a range of steroidogenic enzymes [aromatase, 17beta-hydroxysteroid dehydrogenases (17beta-HSD) type 1, 2 and 4, estrogen sulfotransferase (EST) and steroid sulfatase (STS)] in eutopic and ectopic endometrium of patients (n = 14) with deep-infiltrative endometriosis as well as in disease-free endometrium (n = 48) using real-time PCR and immunocytochemistry. In addition, we evaluated their menstrual cycle-related expression patterns, and investigated their steroid responsiveness in explant cultures.


RESULTS
Aromatase and 17beta-HSD type 1 mRNA levels were extremely low in normal human endometrium, while mRNAs for types 2 and 4 17beta-HSD, EST and STS were readily detectable. Only 17beta-HSD type 2 and EST genes showed sensitivity to progesterone in normal endometrium. Types 1 and 2 17beta-HSD and STS protein was detected in normal endometrium using new polyclonal antibodies.


CONCLUSIONS
In endometriosis lesions, the balance is tilted in favor of enzymes producing E(2). This is due to a suppression of types 2 and 4 17beta-HSD, and an increased expression of aromatase and type 1 17beta-HSD in ectopic endometrium.
Dassen
H
H
Research Institute GROW, University Hospital Maastricht/University Maastricht, Peter Debyelaan, The Netherlands.
Punyadeera
C
C
Kamps
R
R
Delvoux
B
B
Van Langendonckt
A
A
Donnez
J
J
Husen
B
B
Thole
H
H
Dunselman
G
G
Groothuis
P
P
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000201:enzymology*; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D043266:Steryl-Sulfatase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques
D004967:Estrogens; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D043266:Steryl-Sulfatase