ToxSci Advance Access originally published online on January 27, 2006
Toxicological Sciences 2006 91(1):93-103; doi:10.1093/toxsci/kfj120
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Altered Mammary Gland Development in Male Rats Exposed to Genistein and Methoxychlor
* CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709; and Reproductive Toxicology Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Received August 20, 2005; accepted January 2, 2006
Genistein (GE) is a prevalent phytoestrogen whose presence in human and animal foods may affect biological actions of synthetic endocrine active compounds. We have previously reported that in utero and lactational exposure to high doses of GE or the endocrine active pesticide methoxychlor (MXC) caused mammary epithelial proliferation in 21-day-old male rats. Combined exposure to GE and MXC resulted in significant feminization of the male mammary glands. The goals of the current study were to evaluate mammary responses to GE and MXC at the adult stage and investigate relevant mechanisms. Following in utero, lactational exposure (through maternal diet), and direct dietary exposure, the inguinal mammary gland of male rats (90 days of age) was found to exhibit significant morphological alterations in the groups treated with GE and/or MXC compared to the control. GE exposure (at 300 and 800 ppm concentrations) caused lobular enlargement and epithelial proliferation, whereas MXC exposure (800 ppm) led to ductal elongation and lobular enlargement. Combining the two treatments caused prominent proliferation of both ducts and alveoli; secretory material was seen in readily recognizable alveolar lumens, which are absent in untreated male mammary. We also surveyed gene expression in the mammary tissue using a cDNA microarray and evaluated relevant protein factors. The results indicated that the treatment effects are likely due to interactions between steroid hormone receptor–mediated signals and growth factor–driven cellular pathways. The distinctive responses associated with the GE+MXC combination were likely linked to enhanced actions of insulin-like growth factor 1 and related downstream pathways.
Key Words: endocrine disruptor; genistein; methoxychlor; mammary; microarray; insulin-like growth factor 1; ß-catenin; casein.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Penza, C. Montani, A. Romani, P. Vignolini, P. Ciana, A. Maggi, B. Pampaloni, L. Caimi, and D. Di Lorenzo Genistein Accumulates in Body Depots and Is Mobilized during Fasting, Reaching Estrogenic Levels in Serum that Counter the Hormonal Actions of Estradiol and Organochlorines Toxicol. Sci., June 1, 2007; 97(2): 299 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Price, S. K. Murphy, and E. V. Younglai Perspectives: The Possible Influence of Assisted Reproductive Technologies on Transgenerational Reproductive Effects of Environmental Endocrine Disruptors Toxicol. Sci., April 1, 2007; 96(2): 218 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Padilla-Banks, W. N. Jefferson, and R. R. Newbold Neonatal Exposure to the Phytoestrogen Genistein Alters Mammary Gland Growth and Developmental Programming of Hormone Receptor Levels Endocrinology, October 1, 2006; 147(10): 4871 - 4882. [Abstract] [Full Text] [PDF]
|
|