Androgen deprivation induces rapid involution and recovery of human prostate vasculature

Alejandro Godoy, Viviana P. Montecinos, Danny R. Gray, Paula Sotomayor, Jeffrey M. Yau, R. Robert Vethanayagam, Swaroop Singh, James L. Mohler, Gary J. Smith

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

29 Citas (Scopus)

Resumen

The response of the prostate tissue microenvironment to androgen deprivation (AD) represents a critical component in the treatment of benign prostatic hyperplasia and prostate cancer (CaP). Primary xenografts of human benign and CaP tissue transplanted to immunocompromized SCID mice were used to characterize the response of the prostate vasculature during the initial 14 days of AD. Microvessel density and vascular lumen diameter in the prostate xenografts decreased rapidly after AD, reached a nadir on days 2-4, and recovered between days 4 and 14. The number of apoptotic endothelial cells peaked on day 2 after AD and decreased to precastration levels over days 4-7. Leakage of vascular contents in the interstitial space was apparent between days 1 and 3 after AD; however, the vascular permeability barrier reestablished between days 7 and 14. Expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor-2, and basic fibroblast growth factor protein increased in endothelial cells between days 2 and 4 after AD, which preceded vascular recovery and appeared to be a direct and specific response of the endothelial cells to AD. Lack of comparable upregulation of these genes in primary cultures of human prostate endothelial cells in response to AD suggests a role for paracrine signaling mediated through stromal or epithelial cells. VEGF-A expression by prostate endothelial cells appears to represent a key facilitator of the vascular rebound in human prostate tissue induced by removal of circulating testicular androgens.

Idioma originalInglés
Páginas (desde-hasta)E263-E275
PublicaciónAmerican Journal of Physiology - Endocrinology and Metabolism
Volumen300
N.º2
DOI
EstadoPublicada - feb 2011

Áreas temáticas de ASJC Scopus

  • Endocrinología, diabetes y metabolismo
  • Fisiología
  • Fisiología (médica)

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