Brain Research, 506 (1990) 353-357 Elsevier
353
BRES 23901
Melatonin receptors and signal transduction in melatonin-sensitive and melatonin-insensitive populations of white-footed mice (Peromyscus
leucopus) David R. Weaver 1-3, Linda L. Carlson 1'2 and Steven M. Reppert 1-3 1Laboratory of Developmental Chronobiology, Children's Service, Massachusetts General Hospital and 2Department of Pediatrics and ~Program in Neuroscience, Harvard Medical School, Boston, MA 02114 (U.S.A.) (Accepted 19 September 1989) Key words: Melatonin; Cyclic adenosine monophosphate; Receptor autoradiography; Photoperiodism; Pars tuberalis; Median eminence; Reproduction The pineal hormone melatonin times seasonal alterations in reproductive function in photoperiodic mammals. In white-footed mice, there is variation in responsiveness to the reproductive effects of melatonin between populations originating in different locations; mice from Connecticut (CT) respond normally to melatonin, while mice from Georgia (GA) appear insensitive to melatonin. In the present paper, we compare melatonin receptor distribution and a second messenger response to melatonin in white-footed mice from CT and GA. Specific binding of 125I-labeled melatonin (I-MEL) was observed in a variety of brain regions in each population, but there were no consistent differences in the distribution or intensity of I-MEL binding between the populations. Furthermore, melatonin inhibited forskolin-stimulated cAMP accumulation in median eminence/pars tuberalis explants from both populations. These results suggest that insensitivity to melatonin in GA mice is not due to a gross defect in melatonin receptors or receptor-effector coupling. Changes in day length cause dramatic changes in physiology in many mammalian species, including alterations in reproductive function and metabolism. In mammals, the pineal hormone melatonin (N-acetyl5-methoxytryptamine) mediates these effects of daylength (for reviews, see refs. 5, 11, 17, 18). The hypothalamus appears to be the primary site of melatonin action in the regulation of reproduction 5-7'9"11. W e 21"22 and others 12"2°'23 have developed in vitro autoradiographic methods to study high-affinity melatonin receptors using 125I-labeled melatonin (I-MEL; 2[125I]iodomelatonin). In the rodent species examined to date, the distribution of melatonin receptors is remarkably restricted. In rats, Syrian hamsters and Djungarian hamsters, c o m m o n sites of I - M E L binding are the median eminence/pars tuberalis (ME/PT) region and suprachiasmatic nuclei in the hypothalamus and the paraventricular nucleus of the thalamus 22. Other areas are labeled in a species-specific pattern, with relatively few labeled sites detected in each species 22. The site containing the highest concentration of melatonin receptors in these rodent species is the ME/PT region 2
353
BRES 23901
Melatonin receptors and signal transduction in melatonin-sensitive and melatonin-insensitive populations of white-footed mice (Peromyscus
leucopus) David R. Weaver 1-3, Linda L. Carlson 1'2 and Steven M. Reppert 1-3 1Laboratory of Developmental Chronobiology, Children's Service, Massachusetts General Hospital and 2Department of Pediatrics and ~Program in Neuroscience, Harvard Medical School, Boston, MA 02114 (U.S.A.) (Accepted 19 September 1989) Key words: Melatonin; Cyclic adenosine monophosphate; Receptor autoradiography; Photoperiodism; Pars tuberalis; Median eminence; Reproduction The pineal hormone melatonin times seasonal alterations in reproductive function in photoperiodic mammals. In white-footed mice, there is variation in responsiveness to the reproductive effects of melatonin between populations originating in different locations; mice from Connecticut (CT) respond normally to melatonin, while mice from Georgia (GA) appear insensitive to melatonin. In the present paper, we compare melatonin receptor distribution and a second messenger response to melatonin in white-footed mice from CT and GA. Specific binding of 125I-labeled melatonin (I-MEL) was observed in a variety of brain regions in each population, but there were no consistent differences in the distribution or intensity of I-MEL binding between the populations. Furthermore, melatonin inhibited forskolin-stimulated cAMP accumulation in median eminence/pars tuberalis explants from both populations. These results suggest that insensitivity to melatonin in GA mice is not due to a gross defect in melatonin receptors or receptor-effector coupling. Changes in day length cause dramatic changes in physiology in many mammalian species, including alterations in reproductive function and metabolism. In mammals, the pineal hormone melatonin (N-acetyl5-methoxytryptamine) mediates these effects of daylength (for reviews, see refs. 5, 11, 17, 18). The hypothalamus appears to be the primary site of melatonin action in the regulation of reproduction 5-7'9"11. W e 21"22 and others 12"2°'23 have developed in vitro autoradiographic methods to study high-affinity melatonin receptors using 125I-labeled melatonin (I-MEL; 2[125I]iodomelatonin). In the rodent species examined to date, the distribution of melatonin receptors is remarkably restricted. In rats, Syrian hamsters and Djungarian hamsters, c o m m o n sites of I - M E L binding are the median eminence/pars tuberalis (ME/PT) region and suprachiasmatic nuclei in the hypothalamus and the paraventricular nucleus of the thalamus 22. Other areas are labeled in a species-specific pattern, with relatively few labeled sites detected in each species 22. The site containing the highest concentration of melatonin receptors in these rodent species is the ME/PT region 2
