Physiological levels of melatonin enhance gap junction communication in primary cultures of mouse hepatocytes

Gap junction communication is known to be involved in controlling cell prol iferation and differentiation, and seems to play a crucial role in suppress ion of tumor promotion. Melatonin, a hormone secreted by the pineal gland, has putative oncostatic properties. Intercellular communication through gap junctions was assessed by microinjecting Lucifer yellow fluorescent dye in to primary hepatocytes and visualizing the spread of the dye to adjacent ne ighboring cells using phase contrast/fluorescent microscopy. Treatment of p rimary hepatocyte cultures with a physiological range of melatonin concentr ations for 24 h prior to microinjection resulted in significant enhancement in intercellular communication at 0.2 and 0.4 nmol/L but not at lower (0.1 nmol/L) or higher (0.8 or 1.0 nmol/L) concentrations. A time-dependent stu dy showed that the changes in intercellular communication began 10 h after melatonin treatment and reached a maximum at 12 h of treatment. This nonlin ear, functional gap junction response to melatonin occurred in the physiolo gical concentration range detected in blood of mammals during nightly relea ses of the hormone by the pineal gland. These melatonin levels may affect t he ability of gap junction communication to exert cell growth control in vi vo. The uneven decline between individuals in nocturnal release of melatoni n that occurs with age could identify potentially sensitive subpopulations susceptible to developing pathologies involving alterations in biological p rocesses dependent on gap junction communication.