Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*

Abstract

A high-affinity, discretely localized melatonin receptor has been characterized and mapped within the brain and pituitary of the Syrian hamster using the high specific activity ligand [ '251] In mammals, the pineal hormone melatonin is synthesized and secreted into the circulation with a precise nocturnal rhythm (I). The melatonin signal thus acts as an endocrine representation of the dark-phase (2). Melatonin has been shown to influence a variety of processes, including circadian cycles of activity in the rat (3) and seasonal reproductive cyclicity in photoperiodic species such as the sheep and the hamster (1). The mode of action of melatonin is, however, obscure due to the fact that the sites of action of the hormone have remained unidentified. A number of studies have documented relatively lowaffinity melatonin receptors (K, within the nanomolar range) using membrane homogenate receptor assays. The localization of these low-affinity receptors within the brain, pituitary and other tissues is remarkably ubiquitous and, as yet, their physiological significance is unknown (4-9). The widespread distribution found for the low-affinity melatonin receptor contrasts with reports that the photoperiodic effects of melatonin can only be induced by very localized intracerebral administration of the compound (10-12).The use of in vitro receptor-site autoradiography in conjunction with membrane homogenate receptor assays, utilizing the high specific activity ligand [1251]iodomelatonin, has led to the identification of discretely localized melatonin receptors in the brain and pituitary of the foetal and adult hamster (13,14), the adult rat (15-19) and the ovine pituitary (20). Using the same combined approach, we have investigated the distribution and characteristics of a high-affinity melatonin receptor in the brain and pituitary of the adult Syrian hamster, an animal used extensively to study the influence of melatonin on circadian rhythmicity and seasonal reproduction.

Decoding photoperiodic time through Per1 and ICER gene amplitude

“…It has been suggested that this may account for the inability of melatonin injections to entrain circadian activity rhythms in this species (24,25). In this study, and as described previously (17,18), the level of 2-[ 125 I]iodomelatonin binding in the SCN is much lower than in the PT (see Figs. 1 A and 3A), and, therefore, the difference in the Per1 and ICER responses to photoperiod may reflect differences in the sensitivity to melatonin.…”

“…Strong labeling by 2-[ 125 I]iodomelatonin, which is consistent with the localization of melatonin receptors, was observed in the PT and the SCN, but with a lower level of labeling in the SCN (Figs. 1 A and 3A), as described previously (17,18).…”

Occlusion of the Melatonin‐Free Interval Blocks the Short Day Gonadal Response of the Male Syrian Hamster to Programmed Melatonin Infusions of Necessary Duration and Amplitude

“…Iodomelatonin binding sites within the brains of control and compound infusion groups were identified as described previously (23). Rriefly, 20 pm cryostat sections were incubated with 100 pM ['251]iodomelatonin for 30 min at room temperature either alone or in the presence of 1 pM melatonin in Tris-HCI buffer.…”

“…Differences in the gonadal responses of animals to phasic or continuous exposure to melatonin could potentially be a consequence of reduced availability of the melatonin binding sites, resulting from occlusion of the melatonin-free interval. To determine whether such an effect could provide an explanation for differences in the responses to melatonin, the brains of animals were processed post-mortem for in vitro autoradiographic localization of iodomelatonin binding sites (23).…”

Serum leptin profiles, food intake, and body weight in melatonin-implanted Syrian hamsters (Mesocricetus auratus) exposed to long and short photoperiods

“…In the present study, which employed subcutaneous melatonin implants in pineal-intact hamsters, the marked diurnal variation in serum melatonin titers was abolished as a consequence of elevated daytime levels, but rhythmicity in serum melatonin persisted (Figure 3). It must be stressed that melatonin has receptors in the SCN (Williams et al, 1989), and it is possible that, similar to the rhythm in melatonin release, SCN control of leptin release is mainly stimulatory; thus, removal of this stimulatory SCN control results in decreased leptin levels (Karakas and Gündüz, 2006). Choi and Dallman (1999) reported that in SCN-lesion rats, increased plasma leptin levels are accompanied by obesity.…”