Dataset Information

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

ABSTRACT:

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 ([Ca(2+) ]i ), has also been described in a number of cell types. In this study we investigate whether androgens acutely regulate [Ca(2+) ]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 μM). Changes in [Ca(2+) ]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 [Ca(2+) ]i within 1 min of addition. These responses were blocked by the androgen receptor antagonist, flutamide (10 μM); the sarcoplasmic reticulum ATPase pump inhibitor, thapsigargin (1 μM); the inositol trisphosphate receptor inhibitor, 2-aminoethyldiphenyl borate (50 μM) and the PLC inhibitor, U-73122 (1 μM). Responses were also blocked by the L-type calcium channel blocker, nifedipine (1 μM), and by removal of extracellular calcium. A similar transient elevation of [Ca(2+) ]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 [Ca(2+) ]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.

SUBMITTER: Oliver VL

PROVIDER: S-EPMC3791997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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