Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1alpha

The Journal of Endocrinology
Stina Häggström Rudolfsson, Anders Bergh

Abstract

Testosterone-stimulated growth of the ventral prostate (VP) in castrated rats is preceded by angiogenesis, but the mechanisms coordinating vascular and tissue growth are unknown. Adult rats were castrated and some treated with testosterone. Tissue hypoxia was studied morphologically using the hypoxia marker pimonidazole (Hypoxyprobe), hypoxia-inducible factor-1 (HIF-1) alpha, vascular endothelial growth factor (VEGF), and carbonicanhydrase 9 (CA-9) levels by western blotting and quantitative RT-PCR. In the intact untreated prostate, most glands were unstained by the hypoxia marker but already 1 day after castration most epithelial cells in the VP were stained. Seven days after castration prostate glands were apparently normoxic again, and HIF-1alpha, VEGF, and CA-9 were decreased. Treatment of 7-day castrated rats with testosterone resulted in increased epithelial hypoxyprobe staining and increased HIF-1alpha, VEGF, and CA-9 levels. The transient increase in tissue hypoxia after testosterone treatment is probably caused by a temporary mismatch between oxygen consumption and supply. Treatment of prostate epithelial cells in vitro under normoxic conditions also increased HIF-1alpha, and this could be blocked if epidermal growth f...Continue Reading

Citations

May 12, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Philip P FitchevJennifer A Doll
Apr 15, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity·Daniel P SievekingMartin K C Ng
Apr 19, 2011·International Journal of Cancer. Journal International Du Cancer·Indu SinhaRaghu Sinha
Aug 20, 2009·American Journal of Physiology. Endocrinology and Metabolism·Guey-Shyang HwangShyi-Wu Wang
Dec 17, 2010·Medical Hypotheses·Ajit Vikram, Gopabandhu Jena

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