These experiments investigated the way that the effects of melatonin on gonadal activity of ferrets depended upon either reproductive status or environmental lighting conditions. Melatonin (1 mg/day) injected once daily 8 h into the photoperiod prevented the retiming of oestrus by long photoperiods; oestrus occurred in animals treated in this way at the same time as in controls kept under short non-stimulatory photoperiods of 8 h light: 16 h darkness (8L : 16D). This suggests that the 'intrinsic' timing mechanism was not altered by melatonin. Melatonin injected daily into oestrous ferrets terminated oestrus prematurely when the injection was given either 8 or 14 h after the onset of the photoperiod in animals kept under either long (14L : 10D) or short (8L : 16D) photoperiods, though injections given 14 h after onset were more potent in long (but not short) light periods. Melatonin was equally effective in driving pinealectomized ferrets out of oestrus as it was in intact animals.
Melatonin could also induce as well as terminate oestrus in ferrets, but only if injections were discontinued. Thus, shifting the time of two daily injections from 8 and 11 h after 'lights on' to 14 and 17 h was ineffective, but withdrawal of melatonin from anoestrous ferrets (pinealectomized or intact) reliably induced oestrus 4–6 weeks later, irrespective of the lighting conditions. Withdrawal of oil injections had no effect.
These experiments suggest that melatonin acts on the neural mechanisms resetting the timing of oestrus, rather than by a direct 'anti-gonadotrophic' effect. Furthermore, the effect of changes in duration of photoperiod could not be replicated by simply changing the time of melatonin injections to correspond with the presumed night-time surge of endogenous melatonin. Some of the effects of melatonin on retiming oestrus can only be expressed in the absence of melatonin itself.
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