Photic Regulation of mt<sub>1</sub> Melatonin Receptors in the Siberian Hamster Pars Tuberalis and Suprachiasmatic Nuclei: Involvement of the Circadian Clock and Intergeniculate Leaflet

Schuster,; Gauer,; Guerrero, H.; Lakhdar-Ghazal,; Pevet,; Masson-Pevet,

doi:10.1046/j.1365-2826.2000.00039.x

Cited by 43 publications

(34 citation statements)

References 58 publications

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“…With regard to the location of this receptor, it should be noted that the EC itself does not express melatonin receptors (Schuster et al, 2000;Song and Bartness, 2001). A synopsis of several previous studies and our present results indicates that the expression of Dio2 and Dio3 in the EC is regulated via MT1 located in the PT:…”

Section: Discussionsupporting

confidence: 59%

Melatonin Transmits Photoperiodic Signals through the MT1 Melatonin Receptor

Yasuo¹,

Yoshimura²,

Ebihara³

et al. 2009

J. Neurosci.

110

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Melatonin transmits photoperiodic signals that regulate reproduction. Two melatonin receptors (MT1 and MT2) have been cloned in mammals and additional melatonin binding sites suggested, but the receptor that mediates the effects of melatonin on the photoperiodic gonadal response has not yet been identified. We therefore investigated in mice whether and how targeted disruption of MT1, MT2, or both receptor types affects the expression level of two key genes for the photoperiodic gonadal regulation, type 2 and 3 deiodinase (Dio2 and Dio3, respectively). These are expressed in the ependymal cell layer lining the infundibular recess of the third ventricle and regulated by thyrotropin produced in the pars tuberalis. In wild-type C3H mice, Dio2 expression was constantly low, and no photoperiodic changes were observed, whereas Dio3 expression was upregulated under short-day conditions. In C3H with targeted disruption of MT1 and MT1/MT2, Dio2 expression was constitutively upregulated, Dio3 expression was constitutively downregulated, and the photoperiodic effect on Dio3 expression was abolished. Under short-day conditions, C3H with targeted disruption of MT2 displayed similar expression levels of Dio2 and Dio3 as wild-type animals, but they responded to long-day condition with a stronger suppression of Dio3 than wild-type mice. Melatonin injections into wild-type C57BL mice suppressed Dio2 expression and induced Dio3 expression under long-day conditions. These effects were abolished in C57BL mice with targeted disruption of MT1. All data suggest that the melatonin signal that transmits photoperiodic information to the hypothalamo-hypophysial axis acts on the MT1 receptor.

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Section: Discussionsupporting

confidence: 59%

Melatonin Transmits Photoperiodic Signals through the MT1 Melatonin Receptor

Yasuo¹,

Yoshimura²,

Ebihara³

et al. 2009

J. Neurosci.

110

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“…Melatonin is not synthesized in the mouse used in these experiments (C57/B6), as with the majority of mouse strains, and melatonin receptors have not been identified in the ependymal cell layer (22,23).…”

Section: Discussionmentioning

confidence: 98%

Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse

Ivanova

Bechtold

Dupré

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Ivanova EA, Bechtold DA, Dupré SM, Brennand J, Barrett P, Luckman SM, Loudon AS. Altered metabolism in the melatoninrelated receptor (GPR50) knock out mouse. Am J Physiol Endocrinol Metab 294: E176-E182, 2008. First published October 23, 2007 doi:10.1152/ajpendo.00199.2007.-The X-linked orphan receptor GPR50 shares 45% homology with the melatonin receptors, yet its ligand and physiological function remain unknown. Here we report that mice lacking functional GPR50 through insertion of a lacZ gene into the coding sequence of GPR50 exhibit an altered metabolic phenotype. GPR50 knockout mice maintained on normal chow exhibit lower body weight than age-matched wild-type littermates by 10 wk of age. Furthermore, knockout mice were partially resistant to dietinduced obesity. When placed on a high-energy diet (HED) for 5 wk, knockout mice consumed significantly more food per unit body weight yet exhibited an attenuated weight gain and reduced body fat content compared with wild-type mice. Wheel-running activity records revealed that, although GPR50 knockout mice showed no alteration of circadian period, the overall levels of activity were significantly increased over wild types in both nocturnal and diurnal phases. In line with this, basal metabolic rate (O 2 consumption, CO2 production, and respiratory quotient) was found to be elevated in knockout mice. Using in situ hybridization (wild-type mice) and ␤-galactosidase activity (from LacZ insertion element in knockout mice), brain expression of GPR50 was found to be restricted to the ependymal layer of the third ventricle and dorsomedial nucleus of the hypothalamus. GPR50 expression was highly responsive to energy status, showing a significantly reduced expression following both fasting and 5 wk of HED. These data implicate GPR50 as an important regulator of energy metabolism. dorsomedial hypothalamus; metabolic rate; obesity; tanycyte THE ORPHAN MELATONIN RELATED receptor (GPR50) shares ϳ45% homology with melatonin receptors MT 1 and MT 2 (20). However, the receptor does not bind melatonin (13,20) despite the presence of a conserved histidine residue in transmembrane domain 5 of the receptor, which is a key amino acid for binding of melatonin to MT 1 (9). Although the physiological function of GPR50 remains unknown, in situ hybridization studies on mouse, rat, and hamster brain sections have demonstrated an expression of the receptor in several areas associated with energy metabolism, namely the dorsomedial hypothalamic nucleus (DMN), lateral hypothalamus, and arcuate nucleus (12). Although the extent and distribution of GPR50 exhibits some degree of species specificity, high levels of expression are consistently observed in the ependymal layer of the third ventricle (12, 25).Recently, we have shown that ependymal GPR50 expression in the seasonally breeding Siberian hamster is strongly modulated by photoperiod, in which expression is greatly reduced following exposure to short photoperiods (1). Prolonged exposure to short photoperiods leads to a dramatic reduction in ...

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“…It is also well established that melatonin receptors are expressed in high density by cells located in the PT, and that they express TSHB and CGA, whereas the EC, which expresses DIO2 and DIO3, lacks melatonin receptors (20,21). It was therefore tempting to evaluate whether melatonin regulates the expression of TSHB and CGA in the PT and whether TSH may transmit the long-day signal to the EC as shown for the photoperiodic mechanisms in quail.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to mammals, melatonin has little effect on seasonal reproduction in birds (19), which perceive light information for the photoperiodic regulation of reproduction by deep brain photoreceptors. Although melatonin regulates photoperiodic DIO2 and DIO3 expression in the EC of the MBH in mammals (7)(8)(9)(10)(11), melatonin receptor expression could not be found in the EC (20,21). Melatonin receptors are, however, expressed in high density by the thyrotroph cell type in the mammalian PT (22)(23)(24)(25), and photoperiodic regulation of TSH in the PT has been known for several decades (26,27).…”

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confidence: 99%

Involvement of thyrotropin in photoperiodic signal transduction in mice

Ono¹,

Hoshino²,

Yasuo

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

252

241

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Local thyroid hormone catabolism within the mediobasal hypothalamus (MBH) by thyroid hormone-activating (DIO2) and -inactivating (DIO3) enzymes regulates seasonal reproduction in birds and mammals. Recent functional genomics analysis in birds has shown that long days induce thyroid-stimulating hormone production in the pars tuberalis (PT) of the pituitary gland, which triggers DIO2 expression in the ependymal cells (EC) of the MBH. In mammals, nocturnal melatonin secretion provides an endocrine signal of the photoperiod to the PT that contains melatonin receptors in high density, but the interface between the melatonin signal perceived in the PT and the thyroid hormone levels in the MBH remains unclear. Here we provide evidence in mice that TSH participates in this photoperiodic signal transduction. Although most mouse strains are considered to be nonseasonal, a robust photoperiodic response comprising induced expression of TSHB (TSH ␤ subunit), CGA (TSH ␣ subunit), and DIO2, and reduced expression of DIO3, was observed in melatonin-proficient CBA/N mice. These responses could not be elicited in melatonin-deficient C57BL/6J, but treatment of C57BL/6J mice with exogenous melatonin elicited similar effects on the expression of the abovementioned genes as observed in CBA/N after transfer to short-day conditions. The EC was found to express TSH receptor (TSHR), and ICV injection of TSH induced DIO2 expression. Finally, we show that melatonin administration did not affect the expression of TSHB, DIO2, and DIO3 in TSHR-null mice. Taken together, our findings suggest that melatonin-dependent regulation of thyroid hormone levels in the MBH appears to involve TSH in mammals.circadian rhythm ͉ melatonin ͉ pars tuberalis ͉ photoperiodism ͉ type 2 and 3 iodothyronine deiodinases O rganisms living outside the tropics detect and predict seasonal changes in day length (photoperiod) to adapt various metabolic and behavioral functions to the environment. This mechanism, called photoperiodism, allows animals to control the timing of reproduction so that they can raise their offspring in spring and summer when food is most abundant. Among vertebrates, birds possess a highly sophisticated photoperiodic mechanism and show robust responses to photoperiodic changes. Taking advantage of the elaborate avian photoperiodic system, we have recently revealed the gene cascade regulating the photoperiodic response of reproduction in Japanese quail (Coturnix japonica) by using a functional genomics approach (1, 2). Exposure to long days induced thyroid-stimulating hormone (TSH), a heterodimer of the TSH ␤ subunit (TSHB), and the common glycoprotein ␣ subunit (CGA, also called TSH ␣ subunit), in the pars tuberalis (PT) of the pituitary gland. TSH triggers the expression of type 2 iodothyronine deiodinase (DIO2) in the ependymal cells (EC) lining the ventrolateral walls of the third ventricle (i.e., the infundibular recess) within the mediobasal hypothalamus (MBH). DIO2 is a thyroid hormoneactivating enzyme that converts the prohormone thyroxine...

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Photic Regulation of mt₁ Melatonin Receptors in the Siberian Hamster Pars Tuberalis and Suprachiasmatic Nuclei: Involvement of the Circadian Clock and Intergeniculate Leaflet

Cited by 43 publications

References 58 publications

Melatonin Transmits Photoperiodic Signals through the MT1 Melatonin Receptor

Melatonin Transmits Photoperiodic Signals through the MT1 Melatonin Receptor

Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse

Involvement of thyrotropin in photoperiodic signal transduction in mice

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Photic Regulation of mt1 Melatonin Receptors in the Siberian Hamster Pars Tuberalis and Suprachiasmatic Nuclei: Involvement of the Circadian Clock and Intergeniculate Leaflet

Cited by 43 publications

References 58 publications

Melatonin Transmits Photoperiodic Signals through the MT1 Melatonin Receptor

Melatonin Transmits Photoperiodic Signals through the MT1 Melatonin Receptor

Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse

Involvement of thyrotropin in photoperiodic signal transduction in mice

Contact Info

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Photic Regulation of mt₁ Melatonin Receptors in the Siberian Hamster Pars Tuberalis and Suprachiasmatic Nuclei: Involvement of the Circadian Clock and Intergeniculate Leaflet