CLONING EXPERIMENTS AND DEVELOPMENTAL EXPRESSION OF BOTH MELATONIN RECEPTOR ME1(1A) MESSENGER-RNA AND MELATONIN BINDING-SITES IN THE SYRIAN-HAMSTER SUPRACHIASMATIC NUCLEI

The suprachiasmatic nuclei (SCN) are implicated in the control of circ adian biological rhythms, and especially the melatonin nocturnal synth esis. In numerous rodents, melatonin has been shown to feed back on th e SCN activity through high affinity receptors. In contrast, Syrian ha mster SCN activity is unresponsive to melatonin injections. As this la ck of effect could be linked to a developmental loss of SCN melatonin receptors, the goals of the present study were 1) to report in Syrian hamster SCN, and pars tuberalis (PT) as a control, a complete pattern of the postnatal (PN) development of the melatonin receptor density an d 2) to investigate whether the regulation of the Mel(1a) mRNA express ion could be implicated in the post natal variations of the melatonin binding capacities. We first subcloned by PCR a partial cDNA encoding the Mel(1a) receptor from Syrian hamster SCN. Subsequent quantificatio n of Mel(1a) mRNA. expression and melatonin receptor density revealed that in the PT and SCN, both Mel(1a) mRNA expression and melatonin bin ding capacities declined abruptly between PN 0 and PN 8. Afterwards, i n the PT, both parameters went up until they got stabilized in adultho od. Therefore, in the PT, post natal melatonin receptor density variat ions were highly correlated with post natal variations of the Mel(1a) mRNA expression. In the SCN, after PN 8, the melatonin receptor densit y followed its drop and then declined by more than 92% between post na tal day 0 (PN 0) and PN 60 (12.11 +/- 0.27 vs. 0.94 +/- 0.08 fmol/mg p rotein at PN 0 and PN 60 respectively). In contrast, Mel(1a) mRNA expr ession only slightly went down after PN 8 and got stabilized in adult age at 42% of the birth day expression level. These results show that Syrian hamster SCN undergo a dramatic post natal loss of their melaton in receptors that could explain the lack of effect of melatonin inject ions on SCN circadian activity. Furthermore, this SCN binding capaciti es decline could not be attributed to an inhibition of the mRNA expres sion, but rather to a post transcriptional blockade of the Mel(1a), re ceptor expression. (C) 1998 Elsevier Science B.V. All rights reserved.