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Androgens Induce Increases in Intracellular Calcium Via a G Protein–Coupled Receptor in LNCaP Prostate Cancer Cells

From the Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China.

Correspondence to: Dr Ying-hao Sun, Department of Urology, Changhai Hospital, 174 Changhai Road, Shanghai 200433, China.

The receptor mechanism of testosterone-induced nongenomic Ca²⁺ signaling in prostate cancer cells is poorly understood. In this study we investigated androgen-induced intracellular Ca²⁺ increases in LNCaP human prostate cancer cells with Fura-2 as a Ca²⁺ probe. 5-dihydrotestosterone (DHT) produced fast and transient increases in intracellular Ca²⁺ in LNCaP cells in a concentration-dependent manner. These effects were abolished by extracellular Ca²⁺ removal or pretreatment with L-type Ca²⁺ channel inhibitors (nifedipine, verapamil, and diltiazem). Pretreatment with endoplasmic reticulum ryanodine receptor blocker (procaine) or phospholipase C inhibitor (neomycin sulfate) did not alter DHT-induced Ca²⁺ influx. The concentration of Ca²⁺ was also increased by impermeable testosterone conjugated to bovine serum albumin. Neither an antagonist of intracellular androgen receptors (cyproterone acetate) nor a protein synthesis inhibitor (cycloheximide) affected this fast Ca²⁺ influx. Furthermore, the effect of DHT was abolished in cells incubated with a G protein inhibitor (pertussis toxin) and a nonhydrolyzable analog of guanosine triphosphate (guanosine 5-[b-thio]disphosphate) but not in cells incubated with the tyrosine kinase inhibitor genistein. These results indicate that androgens induced an L-type calcium channel–dependent intracellular Ca²⁺ increase in LNCaP prostate cancer cells. The rapid responses triggered by DHT did not appear to be mediated through classic intracellular androgen receptors, c-Src kinase-androgen receptor complex, or sex hormone–binding globulin but through a G protein–coupled receptor in LNCaP prostate cancer cells. These results may provide a new explanation for progression of prostate cancer.

     Key words: 5-Dihydrostestosterone, Ca²⁺, GPCR