MELATONIN RECEPTORS IN BENIGN PROSTATE EPITHELIAL-CELLS - EVIDENCE FOR THE INVOLVEMENT OF CHOLERA AND PERTUSSIS TOXINS-SENSITIVE G-PROTEINSIN THEIR SIGNAL-TRANSDUCTION PATHWAYS

BACKGROUND. Melatonin, the hormone secreted nocturnally by the pineal gland, binds to epithelial cells from the human benign prostate, and c an reduce their growth and viability. The possible involvement of GTP binding proteins cyclic adenosine monophosphate (cAMP) and cyclic guan osine monophosphate (cGMP) in melatonin responses in these cells were investigated. METHODS. The effects of melatonin on cAMP and cGMP were assessed in prostate cells untreated or pretreated with pertussis toxi n (PTX) or cholera toxin (CTX). RESULTS. Melatonin augmented cAMP but reduced cGMP in the epithelial cells (maximal responses at 10 nM). The increase in cAMP was attenuated by PTX, but not by CTX, whereas the d ecrease in cGMP was attenuated by CTX, but not by PTX. CTX, but not PT X, abolished the melatonin-mediated suppression of H-3-thymidine incor poration. In addition, melatonin facilitated the CTX-and PTX-mediated ADP ribosylation of 44- and 41-kilodalton proteins, respectively. The cGMP analogue 8-bromo-cGMP, negated the melatonin-mediated decrease in 3H-thymidine incorporation, whereas H89, a protein kinase A inhibitor , did not inhibit melatonin's effect. CONCLUSIONS. Melatonin receptors in the human benign prostate epithelial cells enhance cAMP and inhibi t cGMP through PTX-and CTX-sensitive G proteins, respectively. The dec rease in DNA synthesis may be secondary to the melatonin-mediated decr ease in cGMP. (C) 1998 Wiley-Liss, Inc.