Melatonin and rat epididymal epithelial cell proliferation: possible mechanisms of actions.

pp. 53-75 of this journal issue entitled: Receptor and Non-Receptor Mediated Actions of Melatonin - International Symposium, Hong Kong, China, November 6-8, 1999Previous studies by our group have demonstrated the presence of putative high affinity 2-[125I]iodomelatonin binding sites in the rat corpus epididymidis, thus indicating a novel direct action of melatonin on the physiology of the epididymis [1]. To explore the possible actions and attendant mechanisms of melatonin on the rat epididymis, the effect of melatonin on the proliferation of corpus-epididymal epithelial cells was studied. Melatonin was found to stimulate rat corpusepididymal epithelial cell proliferation as determined by tritiated thymidine incorporation and flow cytometric analyses. The stimulatory effect of melatonin was dependent on the concentration and duration of exposure to the hormone. Maximal stimulation of [3H]thymidine incorporation into epididymal epithelial cells by melatonin was observed at 1 nM 5•-dihydrotestosterone, while lower or higher concentrations of androgen attenuated the stimulatory effect of melatonin. Interestingly, a MEL1B (MT2) receptor ligand (4-phenyl-2-propionamidotetraline, 4-PPDOT) and a nuclear melatonin receptor agonist (1-[3-allyl-4-oxothiazolidine-2-ylidene]-4-methyl-thiosemi-carbazone, CGP52608) induced, respectively, similar and opposite effects on epithelial cell proliferation to that produced by melatonin. Moreover, epididymal epithelial cell proliferation was inhibited by 8-bromo-cAMP. Given the expression of Gi-coupled MEL1A (mt1) and MEL1B (MT2) receptors in the principal and basal epithelial cells of the rat corpus epididymidis [2], our data suggest that melatonin may act to stimulate epithelial cell proliferation via inhibition of cAMP signaling pathway through MEL1A (mt1) and MEL1B (MT2) receptors in the rat epididymis. It is possible that in young adult rats, MEL1A (mt1) and MEL1B (MT2) receptor-mediated stimulation of epithelial cell proliferation is important for the maintenance of the architectural organization of the functional epithelium in the corpus epididymidis by replacing effete principal and basal cells. References 1 Shiu SYW, Chow PH, Yu ZH, Tang F, Pang SF: Autoradiographic distribution and physiological regulation of 2-[125I]iodomelatonin binding in rat epididymis. Life Sci 1996;59:1165–1174. 2 Li L, Xu JN, Wong YH, Wong JTY, Pang SF, Shiu SYW: Molecular and cellular analyses of melatonin receptormediated cAMP signaling in rat corpus epididymis. J Pineal Res 1998;25:219–228