Colocalization of Androgen Binding Protein, Oxytocin Receptor, Caveolin 1 and Proliferation Marker p21 in Benign Prostate Hyperplasia

Abstract

Androgen-binding protein (ABP) and oxytocin (OT) are among the factors that control smooth muscle proliferation and tumour growth through oxytocin receptor (OTR). A close functional interaction of OTR and caveolin 1 has been shown to modulate cell growth and proliferation. We investigated samples from 10 patients (mean age 68.3) who underwent transurethral prostate resection because of benign prostate hyperplasia (BPH) by immunohistochemistry. Post-mortem prostate samples of three young men (age 18, 28, 33) were used as controls. Tissue samples were embedded in epoxy resin and cut into serial 1 microm sections for colocalization of ABP, OTR, proliferation marker p21 and caveolin 1. ABP was found in stroma of the smooth muscle cells in all studied samples. OTR staining occurred in most of these cells in BPH while controls contained only scattered cells positive for OTR. There were no apparent differences in immunostaining for p21 while immunoreactivity for caveolin 1 was observed in most cells in BPH and only in few cells in controls. Caveolin 1 was mostly colocalized with ABP and OTR in BPH samples while controls did only occasionally show this colocalization. Our observations indicate an interaction of ABP and OTR, associated with caveolin 1, which may account in part for known non-genomic actions of gonadal steroids. Androgen dependent prostate growth in BPH may be linked to these mechanisms.

Oxytocin in the Male Reproductive Tract; The Therapeutic Potential of Oxytocin-Agonists and-Antagonists

“…The prevalence of OTRs inside caveolae has been found to be increased in BPHtissue (37). Both caveolin-1-and OTR-expression increase with age (37) and their colocalization increases in BPH patients (38).…”

“…The similarities of the two nonapeptides and their receptors, and their demonstrated potential to crosstalk underpins current interest in finding more selective OT-and AVP-agonists and -antagonists especially when administering the drug systemically (82). Nevertheless, the classic roles of (38) In epithelial and stromal cells: both peptides are still preserved; where OT is associated with contractile effects and social bonding whereas AVP is associated with water homeostasis and blood pressure regulation. OT acting through AVP-receptors in addition to its own receptor, might account for some of the observed OT side effects because of their possible relation to homeostasis (headache and dizziness).…”

“…Only one OTR-isoform is known to be expressed throughout different tissues. It has been demonstrated by western blotting (WB), real time polymerase chain reaction (RT-PCR) or IHC that the OTR in the human male reproductive tract is present in the testis (59, 60), epididymis (60) and prostate (38,59,60). The OTR was further localized via IHC, immunofluorescence (IF) and WB to the interstitial Leydig cells and Sertoli cells of the testis (59) and the epithelial and stromal cells of the prostate (36,39,54).…”

Age-Dependent Sex Hormone-Binding Globulin Expression in Male Rat

“…SHBG is an active participant in many of these age-associated physiological changes [8]. Jirikowski et al [9] have recently demonstrated that SHBG is co-localized in prostate and benign prostate hyperplasia with oxytocin. The colocalization of these two important endocrine elements in the prostate may suggest an interaction in their function in prostate cells.…”

Imunolocalização dos receptores de ocitocina no testículo e epidídimo de cães

“…Este hormônio exerce um papel fundamental na contração do miométrio no momento do parto e na contração das células mioepiteliais da glândula mamária permitindo a ejeção do leite e lactação, apresentando receptores que circundam os alvéolos e ductos mamários (ANOUAR et al, 1996;FUCHS et al, 1996;REZAPOUR;BACKSTROM;ULMSTEN, 1996;ZINGG, 1996;IVELL, 1997;KIMURA et al, 1998;INABA et al, 1999;BAE;WATSON, 2003;THACKARE;WHITTINGTON, 2006;PRETZER, 2008;LEE et al, 2009;GORDON et al, 2010;LUI et al, 2010;DEBLON et al, 2011;MAGON;KALRA, 2011;CARSON et al, 2013 2 ; KOEHBACH et al, 2013). Outras funções da OT incluem os efeitos no sistema cardiovascular (HATAMI;VALOJERDI;MOWLA, 2007;AHMED;ELOSAILY, 2011;LOPATINA et al, 2012), a regulação da proliferação celular em diferentes tecidos (PETERSSON et al, 2002;HATAMI;VALOJERDI;MOWLA, 2007;SENDEMIR et al, 2008;ZHONG et al, 2010;VRACHNIS et al, 2011), e os efeitos no sistema nervoso central relacionados ao aprendizado, memorização, estresse, desordens neuropsiquiátricas, tendo um papel chave no comportamento social e relacionamento entre os mamíferos (OSTROWSKI, 1998;UVNAS-MOBERG et al, 2001;PRETZER, 2008;…”