AHR signaling in prostate growth, morphogenesis, and disease.
Most evidence of aryl hydrocarbon receptor (AHR) signaling in prostate growth, morphogenesis, and disease stems from research using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pharmacologically activate the AHR at various stages of development. This review discusses effects of TCDD on prostate morphogenesis and highlights interactions between AHR and other signaling pathways during normal and aberrant prostate growth. Although AHR signaling modulates estrogen and androgen signaling in other tissues, crosstalk between these steroid hormone receptors and AHR signaling cannot account for actions of TCDD on prostate morphogenesis. Instead, the AHR appears to act within a cooperative framework of developmental signals to regulate timing and patterning of prostate growth. Inappropriate activation of AHR signaling as a result of early life TCDD exposure disrupts the balance of these signals, impairs prostate morphogenesis, and has an imprinting effect on the developing prostate that predisposes to prostate disease in adulthood. Mechanisms of AHR signaling in prostate growth and disease are only beginning to be unraveled and recent studies have revealed its interactions with WNT5A, retinoic acid, fibroblast growth factor 10, and vascular endothelial growth factor signaling pathways.
Vezina
Chad M
CM
School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
Lin
Tien-Min
TM
Peterson
Richard E
RE
D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D008297:Male; D038081:Organogenesis / Q000187:drug effects / Q000502:physiology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011467:Prostate / Q000196:embryology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D011469:Prostatic Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011987:Receptors, Steroid