Aging and development of ovarian epithelial carcinoma: the relevance of changes in ovarian stromal androgen production.
There are three types of ovarian neoplasms: (1) Those which arise from the surface epithelium covering the ovary. (2) Those which are derived from the cortical mesenchymal stroma. (3) Those which develop from germ cells. Our laboratory has concentrated its effort on solid tumors in women of the first type, epithelial, which has the highest incidence and is the most lethal. Development of these tumors is correlated with aging in the ovary. They form primarily during the perimenopause. Among women, 64% of the total ovarian cancer cases are diagnosed between ages 41 and 60 years. Our approach has been to establish stable tumor cell lines from patient specimens for use as in vitro models. We have investigated the response of these cells to steroid hormones because we hypothesized that these tumors retain some metabolic characteristics which are specific to the ovary. Our data demonstrate that testosterone and androstenedione, but not cortisol, inhibited proliferation of ovarian tumor cells in vitro by a mechanism which was independent of steroid receptors. These androgens are routinely synthesized and secreted by human ovary, and in the menopausal ovary the primary source of androgen is the stromal cell compartment. Because a relatively high local concentration of ovarian androgen exists in vivo, it is possible that androgen may suppress ovarian epithelial carcinoma in women as well. If it does, then development of this carcinoma may be facilitated when the postmenopausal ovary fails to produce adequate androgen during postreproductive years.
Thompson
M A
MA
Department of Obstetrics and Gynecology, S.U.N.Y. Health Science Center, Syracuse 13210.
Adelson
M D
MD
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015994:Incidence; D008593:Menopause; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010053:Ovary / Q000254:growth & development / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000728:Androgens; D009363:Neoplasm Proteins; D013739:Testosterone; D000735:Androstenedione; D001141:Aromatase; D006854:Hydrocortisone