Development of the functional secretory epithelium in the mammary gland of the female mouse requires the elongation of the anlage through the mammary fat pad to form the primary/secondary ductal network from which tertiary ductal side-branches and lobuloalveoli develop. In this study we examined the hormonal requirements for the spatial development of the primary/secondary epithelial network and tertiary side-branches by quantifying ductal growth and epithelial cell proliferation in normal and hormone-treated BALB/c mice between 21 and 39 days of age. In normal mice, an allometric increase in ductal length commenced at 31 days of age and resulted in completion of the primary/secondary ductal network by 39 days of age. Concurrent with this allometric growth was a significant increase in cellular proliferation in the terminal end-buds (TEBs) of the ductal epithelium from 29 days of age, as determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation. A level of cellular proliferation similar to that in the TEBs of 33-day-old control mice could be induced in the TEBs of 25-day-old mice following treatment for 1 day with estrogen (E), or progesterone (P) or both (E/P), indicating that both E and P were mitogenic for epithelial cells of the peripubertal TEBs. However, the period of allometric ductal growth in untreated mice did not correspond to an increase in serum E or P (which might have been expected during the estrous cycle). In addition, epithelial growth was not observed in mammary glands from 24-day-old mice that were cultured in vitro with E, P or E/P. In contrast to treatment with E, treatment with P promoted a dramatic increase, relative to control mice, in the number of tertiary branch points upon the primary/secondary ductal network. BrdU labeling of mammary glands from 24- 33-day-old mice pelleted with cholesterol (C), E, P or E/P confirmed the greater mitogenicity of P on the epithelial cells of the secondary/tertiary ducts as compared with C or E. Concurrent with these changes, localized progesterone receptor (PR) expression in clusters of cells in the ductal epithelium was associated with structures that histologically resembled early branch points from ductules. In conclusion, our results suggest that additional endocrine growth factor(s) other than E and P contribute to the development of the primary/secondary ductal network, and that P is responsible for the formation of tertiary side-branches in the mammary glands of mice during puberty.

This article has been cited by other articles:

				W. V. Ingman and S. A. Robertson Mammary Gland Development in Transforming Growth Factor Beta1 Null Mutant Mice: Systemic and Epithelial Effects Biol Reprod, October 1, 2008; 79(4): 711 - 717. [Abstract] [Full Text] [PDF]

				M. Hiremath, J. P. Lydon, and P. Cowin The pattern of {beta}-catenin responsiveness within the mammary gland is regulated by progesterone receptor Development, October 15, 2007; 134(20): 3703 - 3712. [Abstract] [Full Text] [PDF]

				J. N. Lucas, D. G. Rudmann, K. M. Credille, A. R. Irizarry, A. Peter, and P. W. Snyder The Rat Mammary Gland: Morphologic Changes as an Indicator of Systemic Hormonal Perturbations Induced by Xenobiotics Toxicol Pathol, February 1, 2007; 35(2): 199 - 207. [Abstract] [Full Text] [PDF]

				M. D. Aupperlee, K. T. Smith, A. Kariagina, and S. Z. Haslam Progesterone Receptor Isoforms A and B: Temporal and Spatial Differences in Expression during Murine Mammary Gland Development Endocrinology, August 1, 2005; 146(8): 3577 - 3588. [Abstract] [Full Text] [PDF]

				R. C. Hovey, M. Asai-Sato, A. Warri, B. Terry-Koroma, N. Colyn, E. Ginsburg, and B. K. Vonderhaar Effects of Neonatal Exposure to Diethylstilbestrol, Tamoxifen, and Toremifene on the BALB/c Mouse Mammary Gland Biol Reprod, February 1, 2005; 72(2): 423 - 435. [Abstract] [Full Text] [PDF]

				J. Zhang, C. Wang, P. L. Terroni, F. R. A. Cagampang, M. Hanson, and C. D. Byrne High-unsaturated-fat, high-protein, and low-carbohydrate diet during pregnancy and lactation modulates hepatic lipid metabolism in female adult offspring Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R112 - R118. [Abstract] [Full Text] [PDF]

				M. S. Selvan, A. V. Wilkinson, R. Chamberlain, and M. L. Bondy Social and Dietary Changes Associated with Obesity and Breast Cancer Risk Journal of Health Management, October 1, 2004; 6(2): 103 - 114. [Abstract] [PDF]

				I. Lamote, E. Meyer, L. Duchateau, and C. Burvenich Influence of 17{beta}-Estradiol, Progesterone, and Dexamethasone on Diapedesis and Viability of Bovine Blood Polymorphonuclear Leukocytes J Dairy Sci, October 1, 2004; 87(10): 3340 - 3349. [Abstract] [Full Text] [PDF]

				H. Y. Shi, J. P. Lydon, and M. Zhang Hormonal Defect in Maspin Heterozygous Mice Reveals a Role of Progesterone in Pubertal Ductal Development Mol. Endocrinol., September 1, 2004; 18(9): 2196 - 2207. [Abstract] [Full Text] [PDF]

				I. Gourdou, J. Paly, C. Hue-Beauvais, L. Pessemesse, J. Clark, and J. Djiane Expression by Transgenesis of a Constitutively Active Mutant Form of the Prolactin Receptor Induces Premature Abnormal Development of the Mouse Mammary Gland and Lactation Failure Biol Reprod, March 1, 2004; 70(3): 718 - 728. [Abstract] [Full Text] [PDF]

				J. F. Dorgan, S. A. Hunsberger, R. P. McMahon, P. O. Kwiterovich Jr., R. M. Lauer, L. Van Horn, N. L. Lasser, V. J. Stevens, L. A. Friedman, J. A. Yanovski, et al. Diet and Sex Hormones in Girls: Findings From a Randomized Controlled Clinical Trial J Natl Cancer Inst, January 15, 2003; 95(2): 132 - 141. [Abstract] [Full Text] [PDF]

				P. M. Ismail, J. Li, F. J. DeMayo, B. W. O'Malley, and J. P. Lydon A Novel LacZ Reporter Mouse Reveals Complex Regulation of the Progesterone Receptor Promoter During Mammary Gland Development Mol. Endocrinol., November 1, 2002; 16(11): 2475 - 2489. [Abstract] [Full Text] [PDF]

				J. M. Shillingford, K. Miyoshi, M. Flagella, G. E. Shull, and L. Hennighausen Mouse Mammary Epithelial Cells Express the Na-K-Cl Cotransporter, NKCC1: Characterization, Localization, and Involvement in Ductal Development and Morphogenesis Mol. Endocrinol., June 1, 2002; 16(6): 1309 - 1321. [Abstract] [Full Text] [PDF]

				L. You, M. Sar, E. J. Bartolucci, B. S. McIntyre, and R. Sriperumbudur Modulation of Mammary Gland Development in Prepubertal Male Rats Exposed to Genistein and Methoxychlor Toxicol. Sci., April 1, 2002; 66(2): 216 - 225. [Abstract] [Full Text] [PDF]

				G. Zinser, K. Packman, and J. Welsh Vitamin D3 receptor ablation alters mammary gland morphogenesis Development, January 7, 2002; 129(13): 3067 - 3076. [Abstract] [Full Text] [PDF]