Induction of mammary gland development in estrogen receptor-alpha knockout mice.

TitleInduction of mammary gland development in estrogen receptor-alpha knockout mice.
Publication TypeJournal Article
Year of Publication2000
AuthorsBocchinfuso WP, Lindzey JK, Hewitt SC, Clark JA, Myers PH, Cooper R, Korach KS
JournalEndocrinology
Volume141
Issue8
Pagination2982-94
Date Published2000 Aug
ISSN0013-7227
KeywordsAnimals, Corpus Luteum, Dihydrotestosterone, Estradiol, Estrogen Receptor alpha, Female, Hypertrophy, Mammary Glands, Animal, Mice, Mice, Knockout, Ovariectomy, Pituitary Gland, Progesterone, Prolactin, Receptors, Estrogen
Abstract

Mammary glands from the estrogen receptor-a knockout (alphaERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted ERalpha signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute to the alphaERKO mammary phenotype. We report that circulating PRL is reduced in the female alphaERKO mouse. Implantation of an age-matched, heterozygous ERalpha pituitary isograft under the renal capsule of 25-day-old or 12-week-old alphaERKO mice increased circulating PRL and progesterone levels, and induced mammary gland development. Grafted alphaERKO mice also possessed hypertrophied corpora lutea demonstrating that PRL is luteotropic in the alphaERKO ovary. By contrast, ovariectomy at the time of pituitary grafting prevented mammary gland development in alphaERKO mice despite elevated PRL levels. Hormone replacement using pellet implants demonstrated that pharmacological doses of estradiol induced limited mammary ductal elongation, and estradiol in combination with progesterone stimulated lobuloalveolar development. PRL alone or in combination with progesterone or estradiol did not induce alphaERKO mammary growth. Estradiol and progesterone are required for the structural development of the alphaERKO mammary gland, and PRL contributes to this development by inducing ovarian progesterone levels. Therefore, the manifestation of the alphaERKO mammary phenotype appears due to the lack of direct estrogen action at the mammary gland and an indirect contributory role of estrogen signaling at the hypothalamic/pituitary axis.

Alternate JournalEndocrinology
PubMed ID10919287
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