Sheep as a mammalian model of genetic variability in melatonin.

Large inter-individual variability in plasma melatonin concentration at night is a common mammalian trait. In sheep, it varies from < 50 pg ml(-1) to > 800 pg ml(-1) but is very consistent within individuals. This inter-individual variability is under strong genetic control, which depends on melatonin secretion from the pineal gland, but not on melatonin catabolism. This genetic variability does not originate from differences in the synthetic enzymes or from a difference in melatonin secretion per mg of tissue, but from a difference in pineal size, which is highly variable among lambs of the same age and live weight. The genetic difference among lambs is already expressed at birth and is due to a difference in the number of pinealocytes rather than in their size. Pineal size and number of pinealocytes correlate strongly with plasma melatonin concentrations. The variability in pineal mass is not associated with the variability in any other organ (for example, the pituitary). The identification of genetic markers in the genome associated with the size of the pineal gland may lead to identification of genes involved in development of the mammalian pineal gland. Divergent selection of sheep on the basis of plasma melatonin concentrations could be used to constitute a mammalian model for extreme plasma concentrations.