Progesterone but not estradiol 17beta potentiates local GH secretions by hormone-dependent breast cancer explants. An in vitro study.
The aim of this study was to evaluate the effects of treatment of breast cancer explants with tamoxifen (TMX) or RU486 on GH secretory dynamics in the presence of exogenous estrogen (E2), progesterone (P4) or both. Explants obtained during surgery were divided according to their sex steroid hormone receptor status. P4 (10(-7) M) or 17beta-estradiol (10(-5) M) or both were tested in vitro for their ability to induce hGH secretion and cell proliferation. TMX (10(-7) M) was added to E2, RU486 (10(-7) M) to P4, and both were applied to E2 plus P4-supplemented cultures. The stimulatory action of P4 on GH secretion was noted in hormone-dependent (ER+/PR+) but not in hormone-independent explants (ER-/PR-). RU486 did not abolish this effect. The stimulatory action of P4 on GH release was not parallel to the stimulation of cell proliferation. E2 alone was without effect on GH secretion by both types of breast cancer explants. Combined treatment with both steroids stimulated GH secretion and cell proliferation by (ER+/PR+) explants. Both TMX and RU486 reversed this effect on cell proliferation while only RU486 abolished augmentation of GH secretion. In none of the hormone-dependent breast cancers, the combined treatment with E2 and P4 had any effect on GH secretion and cell proliferation. Taken together, these results lead us to the hypothesis that P4 but not E2 potentiates local GH secretion by hormone-dependent breast cancer explants. The fact that RU486 reversed neither GH secretion nor cell proliferation in hormone-dependent explants indicates its non-receptor-mediated mechanism of action.
Milewicz
T
T
Department of Endocrinology and Fertility, Jagiellonian University, Krakow, Poland.
Gregoraszczuk
E L
EL
Augustowska
K
K
Krzysiek
J
J
Sztefko
K
K
Ryś
J
J
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D015409:Mastectomy, Radical; D011374:Progesterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D019382:Human Growth Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone