The human ovarian surface epithelium is an androgen responsive tissue.
The pathogenesis of epithelial ovarian cancer remains unclear. From epidemiological studies raised levels of androgens have been implicated to increase the risk of developing the disease. The purpose of this study was to determine the responses of normal human ovarian surface epithelium to androgens. We have established primary cultures of human ovarian surface epithelium from patients undergoing oophorectomy for benign disease. Total RNA was isolated from these cultures and expression of mRNA encoding for the androgen receptor was demonstrated using reverse transcriptase polymerase chain reaction. The presence of androgen receptor in sections of normal ovary was also investigated using an antibody against androgen receptor. The effects of androgens on DNA synthesis and cell death were determined. Eight out of eight (100%) cultures expressed mRNA encoding the androgen receptor. The presence of androgen receptor in ovarian surface epithelium of sections of normal ovaries was demonstrated in all sections. Mibolerone, a synthetic androgen, caused a significant stimulation of DNA synthesis in 5 out of 9 (55%) cultures when used at a concentration of 1 nM. Mibolerone also caused a significant decrease in cell death in 2 out of 5 (40%) cultures tested. We have demonstrated that the ovarian surface epithelium is an androgen responsive tissue and that androgens can cause an increase in proliferation and a decrease in cell death. These findings have important implications for the pathophysiology of ovarian carcinogenesis.
Edmondson
R J
RJ
Department of Surgery, University of Newcastle upon Tyne, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. r.j.edmondson@care4free.net
Monaghan
J M
JM
Davies
B R
BR
D000728:Androgens / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000209:etiology*; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D011944:Receptors, Androgen / Q000032:analysis
D000728:Androgens; D011944:Receptors, Androgen; D009277:Nandrolone; C100075:mibolerone