The fallopian tube epithelium is the site of origin for a majority of high grade serous ovarian
carcinomas (HGSOC). The chemical communication between the fallopian tube and the ovary in the development of HGSOC from the fallopian tube is of interest since the fimbriated ends in proximity of the ovary harbor serous tubal
intraepithelial carcinoma (STICs). Epidemiological data indicates that
androgens play a role in ovarian
carcinogenesis; however, the oncogenic impact of
androgen exposure on the fallopian tube, or tubal neoplastic precursor lesions, has yet to be explored. In this report, imaging mass spectrometry identified that
testosterone is produced by the ovary when exposed to tumorigenic fallopian tube derived PTEN deficient cells.
Androgen exposure increased cellular viability, proliferation, and invasion of murine cell models of healthy fallopian tube epithelium and PAX2 deficient models of the preneoplastic secretory cell outgrowths (SCOUTs). Proliferation and invasion induced by
androgen was reversed by co-treatment with
androgen receptor (AR) antagonist,
bicalutamide. Furthermore, ablation of phosphorylated ERK reversed proliferation, but not invasion. Investigation of two hyperandrogenic rodent models of
polycystic ovarian syndrome revealed that peripheral administration of
androgens does not induce fallopian proliferation in vivo. These data suggest that tumorigenic lesions in the fallopian tube may induce an androgenic microenvironment proximal to the ovary, which may in turn promote proliferation of the fallopian tube epithelium and preneoplastic lesions.