Prolactin regulation of estrogen and progesterone receptors in normal and neoplastic mouse mammary tissue.
The transplantable mouse mammary tumor, TPDMT-4, is pregnancy-dependent and requires prolactin (PRL), estradiol (E2) and progesterone (Pg) for growth. To examine the role of PRL in regulating tissue growth and the levels of estrogen receptor (ER) and progesterone receptor (PgR), tumor-bearing mice were ovariectomized, hysterectomized and then injected with ergocornine hydrogenmaleate (ERG), ERG + PRL, or ERG + PRL + E2 + Pg. Total (nuclear + cytoplasmic) ER and PgR in normal and neoplastic mammary tissues were measured. In addition, tumor size and tritium-labeled thymidine [( 3H]dThd) incorporation into nuclei of the tumor and mammary gland were determined. PRL alone caused a 2- to 3-fold increase in ER and PgR levels in normal mammary gland but not in the tumor. PRL alone caused a modest increase in the number of 3H-thymidine-labeled nuclei in both tissues. PRL combined with E2 and Pg increased the percent of labeled nuclei 5- to 10-fold in both tissues, and increased the PgR levels in normal but not in tumor tissue. Thus, PRL alone can increase ER in normal mammary tissue but this increase is not required for growth since ER levels are unchanged when PRL + E2 + Pg are injected and mammary cell growth is stimulated. The ability of PRL to up-regulate ER has been lost in the tumor. Since basal levels of ER and PgR are not altered in the tumor when PRL + E2 + Pg are given, an increase in ER and PgR levels is not required for the three hormones to stimulate tumor growth.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004261:DNA Replication; D005260:Female; D008321:Mammary Glands, Animal / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000503:physiopathology*; D051379:Mice; D010052:Ovariectomy; D011247:Pregnancy; D011388:Prolactin / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D011980:Receptors, Progesterone / Q000502:physiology*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011388:Prolactin