PMID- 18180313
OWN - NLM
STAT- MEDLINE
DCOM- 20080205
LR  - 20191210
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 196
IP  - 1
DP  - 2008 Jan
TI  - Testosterone-stimulated growth of the rat prostate may be driven by tissue 
      hypoxia and hypoxia-inducible factor-1alpha.
PG  - 11-9
LID - 10.1677/JOE-07-0272 [doi]
AB  - 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 factor receptor (EGFR) signaling was blocked with gefitinib. In vivo 
      gefitinib could, however, not block the testosterone induced increase in 
      HIF-1alpha. Testosterone may thus induce HIF-1alpha and its downstream 
      angiogenesis promoting genes by at least two mechanisms, hypoxia and EGFR 
      signaling. Transient epithelial cell hypoxia could by rapidly increasing 
      HIF-1alpha and VEGF be an essential coordinator of testosterone-stimulated 
      vascular and glandular growth.
FAU - Rudolfsson, Stina Haggstrom
AU  - Rudolfsson SH
AD  - Department of Surgical and Perioperative Sciences, Umea University, Umea S-90185, 
      Sweden. stina.rudolfsson@urologi.umu.se
FAU - Bergh, Anders
AU  - Bergh A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Biomarkers)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nitroimidazoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 3XMK78S47O (Testosterone)
RN  - 46JO4D76R2 (pimonidazole)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 4.2.1.1 (Ca9 protein, rat)
RN  - EC 4.2.1.1 (Carbonic Anhydrase IX)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Animals
MH  - Biomarkers/analysis
MH  - Carbonic Anhydrase IX
MH  - Carbonic Anhydrases/analysis
MH  - Cell Hypoxia
MH  - Epithelial Cells/chemistry
MH  - ErbB Receptors/drug effects/physiology
MH  - Gene Expression/drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Male
MH  - Neovascularization, Physiologic
MH  - Nitroimidazoles/analysis
MH  - Orchiectomy
MH  - Prostate/blood supply/*growth & development/metabolism
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Testosterone/*pharmacology
MH  - Vascular Endothelial Growth Factor A/analysis/genetics
EDAT- 2008/01/09 09:00
MHDA- 2008/02/06 09:00
CRDT- 2008/01/09 09:00
PHST- 2008/01/09 09:00 [pubmed]
PHST- 2008/02/06 09:00 [medline]
PHST- 2008/01/09 09:00 [entrez]
AID - 196/1/11 [pii]
AID - 10.1677/JOE-07-0272 [doi]
PST - ppublish
SO  - J Endocrinol. 2008 Jan;196(1):11-9. doi: 10.1677/JOE-07-0272.