MELATONIN BINDING-SITES AND THEIR ROLE IN SEASONAL REPRODUCTION

The pineal gland has a major role in the translation of scotophase dur ation into a hormonal signal by the hormone melatonin. Animals such as sheep, goats and deer use the seasonal variation of this signal to co ordinate reproductive behaviour with the environment. Despite intensiv e research over more than 30 years the site(s) of action of melatonin and the resultant intracellular responses are still not clear. This re view discusses recent work that has localized the site of action of me latonin in sheep using administration into the hypothalamus in vivo as well as studies on putative melatonin receptors in the pars tuberalis and brain. There is clear evidence that melatonin acting at the level of the pars tuberalis is involved in the seasonal regulation of prola ctin secretion, but the evidence for involvement of the pars tuberalis in seasonal reproduction is not compelling. Localized administration of melatonin to the sheep brain revealed that areas anatomically disti nct from the pars tuberalis, the ventromedial and arcuate nuclei, simu lated seasonal reproductive changes in rams and ewes. Recent studies o n brain melatonin binding sites in our laboratory have shown that an a ntagonist of tissue transglutaminase, Bacitracin, as well as substrate s for the enzyme inhibit binding of melatonin to brain membranes. As a working hypothesis, we propose that pineal melatonin secretion alters seasonal reproduction by interactions with a neural transglutaminase at the synapse of neurones involved in the control of GnRH secretion. Synaptic transglutaminase is implicated in the control of the release of neurotransmitter via the synaptic vesicle associated protein, synap sin 1; activation of transglutaminase results in the covalent modifica tion of synapsin 1 such that vesicles are not released from the cytosk eleton. Seasonal variation in the duration of melatonin secretion may result in similar variations in the duration of suppression and activa tion of transglutaminase. The resultant changes in transmitter release may then be responsible for the seasonal neuronal plasticity previous ly observed in GnRH neurones.