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Manganese-induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation in Female Rats
Alina M Hamilton1,2,3, Vinod K Srivastava4, Jill K Hiney4
1School of Integrative Biological and Chemical Sciences, College of Sciences, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA.
Endocrinology
|March 19, 2025
Summary
Precocious puberty (PP) increases hormone receptor-positive (HR+) proliferating cells in mammary glands. Early puberty alters cell regulation, potentially increasing breast cancer risk by promoting high-risk HR+ cells.
Area of Science:
- Endocrinology
- Developmental Biology
- Oncology
Background:
- Precocious puberty (PP) is a known breast cancer risk factor.
- Hormone receptor-positive (HR+) cells in normal mammary glands show limited proliferation.
- The impact of PP on proliferating HR+ cells in the mammary gland remains unclear.
Purpose of the Study:
- To investigate the distribution of HR+ proliferating mammary epithelial cells in prepubertal and adult rats with manganese-induced precocious puberty (MnPP).
- To determine if MnPP alters the characteristics of proliferating HR+ cells in the mammary gland.
Main Methods:
- Female rats were exposed to manganese chloride or saline from postnatal day (PND) 12 to PND 30.
- Mammary glands were analyzed on PNDs 30 and 120 using western blot and immunofluorescence staining.
- Key markers for proliferation (PCNA) and hormone receptors (ER, PR) were assessed.
Main Results:
- MnPP significantly increased the percentage of proliferating HR+ mammary epithelial cells at PND 30.
- Estrogen receptor-regulated proteins (FOXA1, AREG, c-Myc) were upregulated in MnPP mammary glands at PND 30.
- Proliferating HR+ cells remained elevated at PND 120 in MnPP rats, with altered expression of cell-cycle regulators (p27) and progesterone receptor targets (EREG, sp1).
Conclusions:
- Early puberty, induced by MnPP, alters steroidal regulation of mammary gland proliferation.
- This alteration leads to a higher prevalence of high-risk proliferating HR+ cells in the prepubertal mammary gland.
- Findings suggest a mechanism linking precocious puberty to increased breast cancer risk.
