Melatonin is a key hormone that regulates the sleep–wake cycle. Its expression cycles through the day, with changes in the availability of light, and through the year, with changes in the length of the day. It is thought that melatonin is important in the consolidation of sleep, but its action in the brain is not clear. Now, a new study reports the surprising finding that melatonin directly induces the expression of gonadotropin-inhibitory hormones (GnIH) in the avian brain.

GnIH, which is present in both birds and mammals, including humans, is the only neuropeptide identified so far that antagonizes the effect of gonadotropin-releasing hormone on the production of sex steroids such as oestrogen, progesterone and testosterone. According to the current dogma, seasonal changes in melatonin are not involved in the timing of reproduction in birds. However, Ubuka and colleagues thought this might not be the whole story, as several studies have shown that melatonin can reduce gonadal activity and gonadotropin secretion.

To investigate whether melatonin has an effect on reproduction, they surgically removed the main sources of melatonin — the pineal gland and eyes — from the Japanese quail, and measured GnIH expression in the diencephalon. In the absence of melatonin, the levels of GnIH mRNA and peptide drop markedly in neurons in the paraventricular nucleus (PVN) and their terminals in the median eminence. This effect can be reversed by restoring melatonin in these birds, which indicates that the hormone is involved in regulating the synthesis of GnIH.

Melatonin is only expressed at night, and the level of expression depends on the length of the dark phase of the light–dark cycle. To analyse the effect of endogenous melatonin on reproduction, the authors raised male quails under different lighting conditions. Quails that are raised with simulated short days show higher levels of melatonin and GnIH expression than those that are raised with longer periods of light. In addition, the testicular weight of birds raised in short-day conditions is significantly decreased.

So, how does melatonin regulate GnIH synthesis in the PVN? Ubuka et al. found that a melatonin receptor subtype, Mel1C, is expressed in GnIH-expressing neurons in the PVN, and that melatonin binding is significantly higher in the PVN than in surrounding areas. This indicates that melatonin might directly stimulate the production of GnIH in PVN neurons by binding to their receptors.

Interestingly, in Siberian hamsters the expression of the mammalian homologue of GnIH in the brain is also regulated by melatonin. Therefore, GnIH might be an important mediator that translates photoperiodic information, in terms of the melatonin expression level, into an effect on reproduction in both birds and mammals.