A novel androgen signalling pathway uses dihydrotestosterone, but not testosterone, to activate the EGF receptor signalling cascade in prostate stromal cells

Victoria Louise Oliver, Kalliope Poulios, Sabatino Ventura, John Michael Haynes

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9 Citations (Scopus)


Background and Purpose Human prostate growth and function are tightly controlled by androgens that are generally thought to exert their effects by regulating gene transcription. However, a rapid, non-genomic steroid action, often involving an elevation of intracellular calcium ([Ca2+] i), has also been described in a number of cell types. In this study we investigate whether androgens acutely regulate [Ca2+]i in stromal cells derived from the human prostate. Experimental Approach Human-cultured prostatic stromal cells (HCPSCs) were loaded with the calcium-sensitive fluorophore, fura-2-acetoxymethyl ester (FURA-2AM) (10 ?M). Changes in [Ca2+]i in response to the androgens, dihydrotestosterone (DHT) and testosterone, as well as EGF were measured by fluorescence microscopy. Key Results DHT, but not testosterone (0.03-300 nM), elicited concentration-dependent elevations of [Ca2+]i within 1 min of addition. These responses were blocked by the androgen receptor antagonist, flutamide (10 ?M); the sarcoplasmic reticulum ATPase pump inhibitor, thapsigargin (1 ?M); the inositol trisphosphate receptor inhibitor, 2-aminoethyldiphenyl borate (50 ?M) and the PLC inhibitor, U-73122 (1 ?M). Responses were also blocked by the L-type calcium channel blocker, nifedipine (1 ?M), and by removal of extracellular calcium. A similar transient elevation of [Ca2+]i was elicited by EGF (100 ng?mL-1). The EGF receptor inhibitor, AG 1478 (30 nM), and the MMP inhibitor, marimastat (100 nM), blocked the DHT-induced elevation of [Ca2+]i. Conclusions and Implications These studies show that DHT elicits an androgen receptor-dependent acute elevation of [Ca 2+]i in HCPSC, most likely by activating EGF receptor signalling.
Original languageEnglish
Pages (from-to)592 - 601
Number of pages10
JournalBritish Journal of Pharmacology
Issue number3
Publication statusPublished - 2013

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