17-beta-estradiol treatment maintains differentiative potential of virgin mouse mammary gland in culture and its responsiveness to insulin.
Synthesis of the milk proteins, casein and alpha-lactalbumin was not induced in cultured mammary explants from C3H/HeN castrated virgin mice in the presence of lactogenic hormones such as insulin, cortisol and PRL. Replacement therapy with 17-beta-estradiol to the castrated mice completely restored the differentiative potentials of mammary explants, inducing synthesis of the two milk proteins. [3H]thymidine incorporation into DNA synthesized in cultured mammary explants was also decreased by castration to less than 50% (P less than 0.001) of that obtained in intact mice, and 17-beta-estradiol treatment to castrated animals restored DNA synthesis to 90% of the intact level. The addition of insulin to culture medium significantly (P less than 0.001) enhanced [3H]thymidine incorporation into DNA in cultured mammary explants from both intact and 17-beta-estradiol-treated castrated mice but not from castrated animals. Insulin binding sites (1710 +/- 260 sites/cell) to mammary epithelial cells from castrated mice were significantly (P less than 0.05) lower than those from both intact (2870 +/- 300 sites/cell) and 17-beta-estradiol-treated castrated animals (2860 +/- 190 sites/cell). The present findings suggest that 17-beta-estradiol maintains growth and differentiative responses of mammary epithelial cells to insulin, which may be through preserving the number of insulin binding sites in the cells.
Komura
H
H
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Fukui
H
H
Wakimoto
H
H
Miyake
T
T
Terakawa
N
N
Tanizawa
O
O
Matsumoto
K
K
Terada
N
N
D000818:Animals; D002364:Caseins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D007768:Lactalbumin / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D010052:Ovariectomy; D011972:Receptor, Insulin / Q000187:drug effects
D002364:Caseins; D007328:Insulin; D004958:Estradiol; D004247:DNA; D007768:Lactalbumin; D011972:Receptor, Insulin