Do androgens have a direct effect on endometrial function? An in vitro study.
OBJECTIVE
To test the hypothesis that androgens have a direct effect on the function of endometrial epithelial cells.


METHODS
In vitro study.


METHODS
Academic research center.


METHODS
Endometrial epithelial cells were prepared from biopsy samples obtained from normal fertile women.


METHODS
Cells were incubated with androstenedione, testosterone, dihydrotestosterone, and DHEA.


METHODS
Secretion of glycodelin A into the culture fluid was used to assess secretory activity. Uptake of (3)H-thymidine and immunostaining for Ki67 was used to assess cell growth. The specific action of the androgens was confirmed by incubation with an antiandrogen, cyproterone acetate.


RESULTS
Androstenedione (10(-6) M and 10(-7) M) caused a dose-dependent decrease in glycodelin A secretion, uptake of (3)H-thymidine, and percentage of positive Ki67 cells in cultured human endometrial epithelial cells. Testosterone, dihydrotestosterone, and DHEA had no effect on glycodelin A secretion or (3)H-thymidine uptake. The direct effect of androgens on endometrial function were confirmed by demonstrating the presence of androgen receptors in cultured endometrial epithelial cells and showing that the direct effects of the androgens were not observed when cyproterone acetate was added to the cultures.


CONCLUSIONS
The results suggest that androstenedione can inhibit human endometrial cell growth and secretory activity. Infertility and miscarriage associated with high androgen levels (e.g., that caused by the polycystic ovary syndrome) may be due to an adverse effect of high androgen levels on the endometrium.
Tuckerman
E M
EM
Biomedical Research Unit, Jessop Hospital for Women, Sheffield, United Kingdom.
Okon
M A
MA
Li
T
T
Laird
S M
SM
D000728:Androgens / Q000502:physiology*; D000735:Androstenedione / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D002478:Cells, Cultured; D017373:Cyproterone Acetate / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000502:physiology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004717:Endometrium / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D017063:Outcome Assessment, Health Care; D011257:Pregnancy Proteins / Q000378:metabolism; D011863:Radioimmunoassay; D013739:Testosterone / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
D000728:Androgens; D015415:Biomarkers; D000071816:Glycodelin; D006023:Glycoproteins; D019394:Ki-67 Antigen; C045246:PAEP protein, human; C489047:Paep protein, mouse; D011257:Pregnancy Proteins; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D017373:Cyproterone Acetate; D013936:Thymidine