Growth regulation effects of gonadotropin induced steroidogenic response in human ovarian cancer.
BACKGROUND
Despite a substantial body of epidemiological evidence, there is only a limited indication that gonadotropins and steroids have growth regulating functions in ovarian cancer. To elucidate the role of gonadotropins in regulating steroid metabolism in human ovarian cancer, we analyzed the modulation of estradiol secretion by FSH and hCG and the gonadotropic regulation of hCG secretion in vitro. Furthermore, we analyzed estradiol and hCG levels in serum and cyst fluids of patients with ovarian cancer.


METHODS
OVCAR3 cells were incubated with estradiol (1, 5, 10 nM), FSH (100 microg/L) and hCG (10, 25 microg/L). Growth stimulation was evaluated by MTT assay. Estradiol was measured in the supernatant after incubation with hCG and FSH, while hCG was measured after FSH incubation. FSH, estradiol and hCG levels were measured in serum and cyst fluids of patients with ovarian cancer.


RESULTS
OVCAR3 cells responded to hCG and FSH by increased estradiol secretion (p<0.001), while estradiol led to a dose-dependent stimulation of cell growth (p<0.05). 100 microg/L FSH led to a 75% decrease of hCG secretion (p<0.001).


CONCLUSIONS
Gonadotropins stimulate estradiol secretion in ovarian cancer cells and modulate steroid dependent growth stimulation. FSH modulates hCG related growth stimulation in ovarian cancer. These results were supported by in vivo measurements in ovarian cancer patients.
Kraemer
S
S
Department of Obstetrics and Gynecology, University of Erlangen-Nuremberg, Erlangen, Germany. stefan.kraemer@gyn.med.uni-erlangen.de
Jaeger
W H
WH
Lang
N
N
D002455:Cell Division; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D005640:Follicle Stimulating Hormone