Effects of estradiol and progestogens on human breast cells: regulation of sex steroid receptors.
OBJECTIVE
To examine the effects of 17β-estradiol (E2) and progestogens, used in hormone therapy, on estrogen receptors (ER), progesterone receptors (PR), and human breast tumor cell growth.


METHODS
MCF-7 cells were incubated in pure E2 (1 nM and 10 nM) as well as in E2 in conjunction with 10 nM progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NET), and cyproterone acetate (CPA). Cell proliferation, apoptosis, expression of caspase-3, and both ER and PR isoforms were evaluated.


RESULTS
Caspase-3 was significantly diminished in cultures with only E2, whereas ERα significantly increased. A significant increase of caspase-3 in addition to the entire abolishment of E2-induced augmentation of ERα was observed in 1 nM E2 plus MPA and 10 nM E2 plus NET, whereas PR isoform B (PRB) was significantly increased. The ratios of apoptosis: proliferation significantly increased in 1 nM E2 plus progestogens (except P4) and 10 nM E2 plus NET. The changes of the PRA/PRB ratio were inversely related to the changes of the apoptosis to proliferation ratio. Significant increase of ERβ and PRB was noted in the E2 plus MPA or NET, in addition to a significant increase of ERα and decrease of PRA in the E2 plus CPA, as well as an increase of ERα and decrease of PRA and PRB in the E2 plus P4.


CONCLUSIONS
The combination of E2 and various progestogens resulted in diverging effects on ERs and PRs expressions, which induced different effects on MCF-7 cell growth. Compared with P4, aberrant hormone and biological activity of synthetic progestin, by way of altered receptor expression, may be an important factor in affecting breast cell growth.
Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taiwan. Electronic address: fangping@cgmh.org.tw.
Fang-Ping
FP
Chen
Mei-Hua
MH
Chien
Huang-Yang
HY
Chen
Ting-Shuo
TS
Huang
Yuet-Tong
YT
Ng
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D017373:Cyproterone Acetate / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D017258:Medroxyprogesterone Acetate / Q000378:metabolism / Q000494:pharmacology; D009640:Norethindrone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000077563:Norethindrone Acetate; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000378:metabolism / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011372:Progestins; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone; D017373:Cyproterone Acetate; D004958:Estradiol; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; C505407:CASP3 protein, human; D053148:Caspase 3; D009640:Norethindrone
17-β-estradiol; caspase-3; estrogen receptor; progesterone receptor; progestogen