PPAR Research (Jan 2008)

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

DOI
https://doi.org/10.1155/2008/651419
Journal volume & issue
Vol. 2008

Abstract

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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.