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INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE
Citation:
Bocchinfuso, W. P., J. K. Lindzey, S. C. Hewitt, J. A. Clark, P. H. Myers, R L. Cooper, AND K. S. Korach. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE. ENDOCRINOLOGY 141(8):2982-2994, (2000).
Description:
Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute to the ERKO mammary phenotype. We report that circulating prolactin in reduced in the female ERKO mouse. Implantation of an age-matched ER -positive pituitary isograft under the renal capsule of 25 day or 12 week old ERKO mice increased circulating prolactin and progesterone levels, and induced mammary gland development. Grafted ERKO mice also possessed hypertrophied corpora lutea demonstrating that prolactin in luteotropic in the ERKO ovary. By contrast, ovariectomy at the time of pituitary grafting prevented mammary gland development in ERKO mice despite prolactin levels remaining elevated. 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. Prolactin alone or in combination with progesterone or estradiol did not induce ERKO mammary growth. Estradiol and progesterone are required for the structural development of the ERKO mammary gland, and prolactin contributes to this development by inducing ovarian progesterone levels. Therefore, the manifestation of the ERKO mammary phenotype appears due to the lack of both direct estrogen action at the mammary gland and an indirect contributory role of estrogen signaling at the hypothalamic/pituitary axis.