The development of melatonin-binding sites in the ovine fetus

Abstract

The pineal hormone, melatonin, is important in the timing of seasonal reproduction in the sheep. Melatonin of maternal origin readily crosses the placenta; its function in the fetal sheep is, however, unclear. To gain an insight into the role of melatonin in ovine development we have identified specific melatonin receptors throughout gestation using 2-[125I]iodomelatonin and quantitative in vitro autoradiography. Specific binding was found at the earliest time studied at 30 days of gestation, over the developing thyroid (term = 145 days). At 31 days of gestation specific labelling was found over the thyroid and pituitary glands, the spinal nerves, nasal cavity and developing bronchi. This binding was diminished by over 50% in the presence of 10(-4) M GTP gamma S (an analogue of guanosine triphosphate) indicating that the 2-[125I]iodomelatonin binding at this early stage of gestation represents a receptor coupled to a regulatory G-protein. By 40 days of gestation specific binding was found over the nasal epithelium, cochlear epithelium, regions of the brain, especially the hind brain and the vestibulocochlear and glossopharyngeal nerves, and both the pars distalis and pars tuberalis of the pituitary. As gestation proceeded, labelling over the pars distalis appeared to become more scattered in nature while that on the pars tuberalis remained consistent. Saturation studies of both the neuronal and pituitary binding sites at 121 days of gestation and in the newborn lamb revealed a single class of high-affinity binding sites with Kd values in the picomolar range. Also at 121 days of gestation, binding over the fetal pars tuberalis was diminished in a dose-dependent manner by GTP gamma S, again confirming that specific binding is indicative of a receptor coupled to a regulatory G-protein. These data demonstrate a potential for sensitivity to melatonin from early in gestation, as well as the developmentally specific expression of the melatonin receptor in certain tissues, and suggest a wider role for melatonin in ovine fetal development than previously considered.

Encoding and Decoding Photoperiod in the Mammalian Pars Tuberalis

“…First, the early development of the PT combined with the specific expression of MT1 suggests an important role for melatonin during neonatal life [49]. Indeed, a correlation between changes in prenatal photoperiodic exposure and gonadal development or gene expression in the PT have been described [50,51,52,53,54].…”

What is the role of melatonin within the anterior pituitary?

“…In fetal and newborn animals, melatonin receptors are expressed more widely, both in the CNS and in the pituitary (Williams et al 1991, Helliwell & Williams 1994, and in other tissues in which expression is absent in the adult (e.g. the developing renal cortex (Drew et al 1998)).…”

“…As a model tissue for understanding melatonin action, the anterior pituitary is advantageous in that it contains (in the pars tuberalis (PT)) the highest concentration of melatonin receptors of all mammalian tissues ; moreover, compared with neurones, anterior pituitary cells are comparatively amenable to analysis at a cellular level. As well as modulating the PRL axis, melatonin-responsive cells within the pituitary are of biological interest because, in the pars distalis (PD) of both the rat and the sheep, a clear developmental loss of expression occurs over the perinatal period (Vanecek 1988, Williams et al 1991, Helliwell & Williams 1994. This suggests that melatonin receptors are involved in the control of aspects of anterior pituitary function which are specific to the perinatal period.…”

Melatonin receptors in the human fetal kidney: 2-[125I]iodomelatonin binding sites correlated with expression of Mel1a and Mel1b receptor genes

“…However, based on the identification of putative melatonin binding sites in peripheral tissues such as the intestine (Pointoire et al 1993), cerebral arteries (Viswanathan et al 1993) and kidney (Song et al 1993(Song et al , 1995a(Song et al ,b, 1997 it is now thought that melatonin may have a potentially wider role than the control of seasonal and circadian rhythmicity. Furthermore, the identification of 2-[ 125 I]iodomelatonin binding sites in the fetuses of a number of different species, including the rat (Williams et al 1991), sheep (Helliwell & Williams 1994), hamster (Weaver et al 1988, Carlson et al 1991, Rivkees & Reppert 1992) and the human (Yuan et al 1991), is indicative of a further function for melatonin in fetal development. Maternal melatonin has been shown to be transferred to the fetus in sheep (Yellon & Longo 1988), hamsters (Weaver et al 1988), rats (Klein 1972) and non-human primates (Reppert et al 1979) and to influence hormonal status in the fetus and in the neonate (Bassett et al 1988, 1989, Ebling et al 1989.…”