1. Photoperiodicity
In seasonally breeding animals, information about the time of year is crucial to reproductive success and the role of the pineal gland in obtaining and conveying this information was described in section III.B, Figure 1. Examples of seasonal functions of melatonin include, in addition to those required for successful reproduction, changes in the growth and color of the coat and appetite changes in preparation for or recovery from hibernation. As a species, humans do not dis play overt seasonality in reproductive events, although those who live near the Arctic circle have been reported to have decreased pituitary function and conception rates during the winter darkness (when melatonin levels are high) relative to those in the summer.
Fig1. Patterns of melatonin secretion. A. The pineal conveys information about the light–dark cycle of the current day because melatonin is secreted only during darkness. Serum levels of melatonin rise several-fold to a peak in the midpoint of the dark cycle. Peak melatonin levels are seen during childhood and decrease progressively during adulthood and aging. B. The pineal gland also conveys seasonal information by varying with the length of days. As the areas under these two curves indicate, the shorter the day, the more melatonin is produced and the longer it is present in the bloodstream.
2. Melatonin and the Hypothalamic- Pituitary Axis
In nonprimates, the seasonal and other effects of melatonin on the reproductive axis are exerted through inhibition of GnRH at the hypothalamus, leading to decreased gonadotrophin secretion from the pituitary and a dampening effect on the reproductive organs. In humans, a negative correlation between nocturnal serum LH and melatonin levels during the night has been reported and clinical observations support this relationship. For example, women who experience exercise-induced amenorrhea have high serum melatonin levels. In both normal and hypogonadic men melatonin suppresses gonadotrophin secretion. The mechanism of melatonin inhibition of GnRH secretion is not certain, but recently it has been suggested that kisspeptin neurons may mediate these effects.
3. Melatonin and Puberty
The hypothalamic-pituitary-gonadal axis is active in the human fetus but after the first year of life it becomes quiescent until approximately the age of 10 years, when an increase in the pulses of GnRH secretion lead to increased gonadotrophin levels. Melatonin levels peak during child hood and begin to fall around the end of the first decade, suggesting that the diminution of inhibition of the hypothalamic-pituitary axis by melatonin may be involved in the timing of the onset of puberty. In children with precocious puberty (prior to the age of 9–10) or delayed puberty (later than 13–14 years old) nocturnal levels of melatonin secretion are, relative to age-matched control children, low or high, respectively. These observations support an association between melatonin secretion and the timing of human puberty but do not provide evidence of a causal relationship between the two processes.
4. Melatonin in Pregnancy and Parturition
Pre-eclampsia is a medical condition of late pregnancy characterized by high blood pressure and urinary protein loss. If untreated it can lead to eclampsia, seizures during labor, which can be life-threatening. Patients with severe pre-eclampsia have lower nocturnal melatonin secretion than normal pregnant women at the same stage of pregnancy, suggesting a blood pressure-lowering role for melatonin. This is supported by observations that humans have lower blood pressure, heart rate, and cardiac output at night than during the day. Another aspect of melatonin in pre-eclampsia is its possible role in reducing the oxidative stress which is thought to contribute to this condition in pregnancy.
The onset of labor (parturition) in humans tends to occur more often during the night (midnight to 5 am) than at other times during the day. Recent observations that uterine receptors for melatonin and oxytocin (the hormone responsible for uterine contractions) increase in parallel at the onset of labor indicates that melatonin could be the circadian signal that underlies its timing.
