Activation of Penile Proadipogenic Peroxisome Proliferator-Activated Receptor š¯›¾ with an Estrogen: Interaction with Estrogen Receptor Alpha during Postnatal Development
Mahmoud M. Mansour,
Hari O. Goyal,
Tim D. Braden,
John C. Dennis,
Dean D. Schwartz,
Robert L. Judd,
Frank F. Bartol,
Elaine S. Coleman,
Edward E. Morrison
Affiliations
Mahmoud M. Mansour
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Hari O. Goyal
Department of Biomedical Sciences, Tuskegee University, Tuskegee, AL 36088, USA
Tim D. Braden
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
John C. Dennis
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Dean D. Schwartz
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Robert L. Judd
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Frank F. Bartol
Cellular and Molecular Biosciences Program, Department of Animal Sciences, Auburn University, Auburn, AL 36849, USA
Elaine S. Coleman
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Edward E. Morrison
Departments of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Exposure to the estrogen receptor alpha (ERš¯›¼) ligand diethylstilbesterol (DES) between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ERš¯›¼ and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARš¯›¾). Transcripts for PPARs š¯›¼, š¯›½, and š¯›¾ and š¯›¾1a splice variant were detected in Sprague-Dawley normal rat penis with PPARš¯›¾ predominating. In addition, PPARš¯›¾1b and PPARš¯›¾2 were newly induced by DES. The PPARš¯›¾ transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPARš¯›¾ protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ERš¯›¼ and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPARš¯›¾ expression. These results suggest a biological overlap between PPARš¯›¾ and ERš¯›¼ and highlight a mechanism for endocrine disruption.
