Biomedical subjects

J G Mercer

Publications and source records attributed to J G Mercer.

At least 19 recordsLinked to original sources

PubMed2007

G protein-coupled receptor 101 mRNA expression in the mouse brain: altered expression in the posterior hypothalamus and amygdala by energetic challenges.

GPCR101 is a recently identified orphan G protein-coupled receptor (GPCR) expressed abundantly in the human and mouse hypothalamus. In the absence of a ligand, a direct approach to determine the function(s) of this receptor is not possible. However, clues to the possible functions of GPCR101 may yield from information on the distribution of the receptor and the effect of in vivo manipulation upon the expression level of the receptor. In situ hybridisation on mouse brain sections revealed GPCR101 expression in a number of nuclei, including the amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, as well as in the arcuate nucleus, posterior hypothalamus and paraventricular nucleus of the hypothalamus. Food-deprivation was found to increase GPCR101 mRNA level in the posterior hypothalamus and amygdala. In obese mice bearing the ob gene mutation, GPCR101 mRNA level decreased in the posterior hypothalamus and remained unaltered in the amygdala. By contrast, in both nuclei, GPCR101 mRNA level did not change significantly in obese ob/ob mice after intraperitoneal injection of leptin or in mice fed with a high fat diet. These data suggest that GPCR101 mRNA expression in the posterior hypothalamus and amygdala is regulated by a factor(s) other than leptin. Dual in situ hybridisation was used to establish the relationship between GPCR101 and neuropeptides expressed in the hypothalamus. In the arcuate nucleus, GPCR101 mRNA was expressed in approximately half of the population of neurones expressing the mRNA for the anorexigenic neuropeptide, pro-opiomelanocortin, which suggests a potential functional relationship.

Amygdala↗

PubMed2007

Altered expression of SOCS3 in the hypothalamic arcuate nucleus during seasonal body mass changes in the field vole, Microtus agrestis.

We have previously shown that cold-acclimated (8 degrees C) male field voles (Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD, 16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than animals maintained in SD. By infusing voles with exogenous leptin, we have also demonstrated that SD voles respond to the hormone by reducing body mass and food intake, whereas LD animals increasing body mass are resistant to leptin treatment. In the present study, we investigated whether seasonal changes in body mass could be linked to modulation of the leptin signal by suppressor of cytokine signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up to 11 weeks. LD voles increasing body mass had significantly higher levels of SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated changes in expression of NPY, AgRP, POMC and CART genes. These results suggest that voles that regulate body mass at either the lower (SD) or upper (LD) plateau remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a short-term mechanism that enables animals to move between the stable body mass plateaus. Our data provide evidence that expression of SOCS3 in the ARC is involved in the modulation of the strength of the leptin signal to facilitate seasonal cycles in body mass and adiposity.

Acclimatization↗

PubMed2006

The suppressor of cytokine signalling 3, SOCS3, may be one critical modulator of seasonal body weight changes in the Siberian hamster, Phodopus sungorus.

The Siberian hamster, Phodopus sungorus, exhibits a remarkable cycle of body weight, reproduction and leptin sensitivity in response to a seasonal change in photoperiod. In the present study, we investigated the hypothesis that the suppressor of cytokine signalling 3 (SOCS3) plays a critical role in the regulation of the seasonal body weight cycle. We analysed arcuate nucleus SOCS3 gene expression in short day length (SD; 8 : 16 h light/dark) acclimated Siberian hamsters that were transferred back to long day length (LD; 16 : 8 h light/dark) and in hamsters that spontaneously became photorefractory to SD induced by prolonged exposure. SD acclimated hamsters that were transferred back to LD for 1, 2, 3, 4 or 6 weeks, increased arcuate nucleus SOCS3 gene expression to the LD level within 2 weeks, and maintained this higher level thereafter. The early increase of SOCS3 gene expression preceded the LD-induced rise in body weight by approximately 3 weeks. Hamsters kept in SD for an extended period (25 weeks), began to become refractory to SD and to increase body weight. By this time, there was no difference in level of SOCS3 gene expression between LD and SD photoperiods, although body weight was still suppressed in SD hamsters. Finally, we addressed whether SOCS3 gene expression is related to SD-induced gonadal regression or to body weight decrease by comparing Siberian hamsters with Syrian hamsters. The latter exhibited substantial SD-induced gonadal regression but only limited seasonal changes in body weight. Acclimation to either LD or SD for 14 weeks had no effect on SOCS3 gene expression. This implies that arcuate nucleus SOCS3 gene expression is unlikely to be related to seasonal cycles in reproductive activity. Taken together, the findings further strengthen our hypothesis that SOCS3 may be one molecular trigger of seasonal cycles in body weight.

Acclimatization↗

PubMed2006

PC1/3 and PC2 gene expression and post-translational endoproteolytic pro-opiomelanocortin processing is regulated by photoperiod in the seasonal Siberian hamster (Phodopus sungorus).

A remarkable feature of the seasonal adaptation displayed by the Siberian hamster (Phodopus sungorus) is the ability to decrease food intake and body weight (by up to 40%) in response to shortening photoperiod. The regulating neuroendocrine systems involved in this adaptation and their neuroanatomical and molecular bases are poorly understood. We investigated the effect of photoperiod on the expression of prohormone convertases 1 (PC1/3) and 2 (PC2) and the endoproteolytic processing of the neuropeptide precursor pro-opiomelanocortin (POMC) within key energy balance regulating centres of the hypothalamus. We compared mRNA levels and protein distribution of PC1/3, PC2, POMC, adrenocorticotrophic hormone (ACTH), alpha-melanocyte-stimulating hormone (MSH), beta-endorphin and orexin-A in selected hypothalamic areas of long day (LD, 16:8 h light:dark), short day (SD, 8:16 h light:dark) and natural-day (ND, photoperiod depending on time of the year) acclimated Siberian hamsters. The gene expression of PC2 was significantly higher within the arcuate nucleus (ARC, P < 0.01) in SD and in ND (versus LD), and is reflected in the day length profile between October and April in the latter. PC1/3 gene expression in the ARC and lateral hypothalamus was higher in ND but not in SD compared to the respective LD controls. The immunoreactivity of PC1/3 cleaved neuropeptide ACTH in the ARC and PC1/3-colocalised orexin-A in the lateral hypothalamus were not affected by photoperiod changes. However, increased levels of PC2 mRNA and protein were associated with higher abundance of the mature neuropeptides alpha-MSH and beta-endorphin (P < 0.01) in SD. This study provides a possible explanation for previous paradoxical findings showing lower food intake in SD associated with decreased POMC mRNA levels. Our results suggest that a major part of neuroendocrine body weight control in seasonal adaptation may be effected by post-translational processing mediated by the prohormone convertases PC1/3 and PC2, in addition to regulation of gene expression of neuropeptide precursors.

Adaptation, Physiological↗

PubMed2005

Photoperiod regulates leptin sensitivity in field voles, Microtus agrestis.

We have previously shown that cold-acclimated (8 degrees C) male field voles (Microtus agrestis) transferred from short (SD, 8:16 h L:D) to long photoperiod (LD, 16:8 h L:D) exhibit increases in body mass, adiposity and food intake. To assess whether these increases were associated with decreased leptin sensitivity, we infused LD and SD voles with physiological doses of murine leptin (or saline) delivered peripherally for 7 days via mini-osmotic pumps. Measurements were made of body mass (weight-reducing effect of leptin), food intake (anorectic effect of leptin) and gene expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) (thermogenic effect of leptin). The SD animals were sensitive to the weight-reducing effects of leptin (mean body mass decrease of 1.2 g over 7 days) and appetite-reducing effect of leptin (mean food intake decrease of 2.5 g over 7 days), whereas LD voles were resistant to the hormone treatment. The switch from a leptin-sensitive to leptin-resistant state appears to act as a desensitisation mechanism that allows voles transferred from SD to LD to ignore elevated leptin levels generated by increased body fat and accumulate adipose tissue without stimulating compensatory changes opposing the weight gain. Neither SD nor LD voles responded to infusion of leptin by changes in BAT UCP1 gene expression, suggesting dissociation of anorectic and thermogenic effects of leptin, possibly related to chronic cold exposure. Our results indicate that cold-acclimated voles show photoperiod-regulated changes in leptin sensitivity and may provide an attractive model for elucidating molecular mechanisms of leptin resistance.

Acclimatization↗

PubMed2005

Diet-induced obesity in the Sprague-Dawley rat: dietary manipulations and their effect on hypothalamic neuropeptide energy balance systems.

The SD (Sprague-Dawley) rat model of DIO (diet-induced obesity) is reported to exhibit a clear segregation into susceptible and resistant subpopulations shortly after transfer to a HE (high energy) diet. This does not appear to be the case for rats sourced in the U.K., where body weight gain on obesogenic HE diet is normally distributed, as might be anticipated for a polygenic trait in an outbred population. Many of the energy balance effects of dietary manipulation in this model (e.g. supplementation of HE diet with the liquid diet, Ensure; energy intake and defence of body weight following withdrawal of obesogenic diet) appear to be characteristics of the diets being manipulated rather than subject traits. The activities of energy balance-related hypothalamic signals are affected by diet and the development of DIO, but may not be able to differentiate between different diets and the relative levels of obesity that develop.

Animals↗

PubMed2005

Introduction of a high-energy diet acutely up-regulates hypothalamic cocaine and amphetamine-regulated transcript, Mc4R and brown adipose tissue uncoupling protein-1 gene expression in male Sprague-Dawley rats.

Obesity is an escalating problem in Western societies. Susceptibility to weight gain within an obesogenic environment is variable. It remains unclear how the range of weight gain responses are generated. It is possible that an individual's immediate and/or sustained appetite for apparently palatable foods, or metabolic adaptations to a new diet could be important. The present study therefore examined the short- to medium-term effects of a high-energy (HE) diet on bodyweight, food intake, and energy balance-related signalling systems. Sprague-Dawley rats were fed either chow or an HE diet for 12 h, 24 h, 48 h or 14 days. Blood hormones and metabolites were assayed, and expression of uncoupling protein-1 (UCP-1) and hypothalamic energy-balance related genes were determined by Northern blotting or in situ hybridisation, respectively. Short-term exposure (12 h, 24 h, 48 h) to the HE diet had no effect on grams of food consumed, but caloric intake was increased. Exposure to HE diet for 14 days (medium term) established a bodyweight differential of 7.7 g, and animals exhibited a transient increase in caloric intake of 5 days duration. Terminal levels of leptin, insulin, glucose and non-esterified fatty acids (NEFAs) were all increased in HE-fed animals. UCP-1 mRNA was elevated in interscapular brown adipose tissue from HE-fed rats only at 12 h. Cocaine and amphetamine-regulated transcript (CART) and Mc4R gene expression in the hypothalamus were increased after 12 h and 24 h on an HE diet, respectively. The rats appear to passively over-consume calories as a result of consuming a similar weight of a more energy dense food. This evokes physiological responses, which adjust caloric intake over several days. Circulating NEFA and insulin concentrations, UCP-1, Mc4R and CART gene expression are increased as an immediate consequence of consuming HE diet, and may be involved in countering hypercaloric intake. Circulating leptin is increased in the HE-fed animals after 48 h, reflecting their increasing adiposity.

Animal Feed↗

PubMed2005

Hypothalamic energy balance gene responses in the Sprague-Dawley rat to supplementation of high-energy diet with liquid ensure and subsequent transfer to chow.

Energy dense, high fat, high sugar, foods and beverages in our diet are a major contributor to the escalating global obesity problem. Here, we examine the physiological and neuroendocrine effects of feeding rats a solid high-energy (HE) diet with or without a liquid supplement (Ensure) and the consequence of subsequently transferring animals back to chow (C). Outbred Sprague-Dawley rats were fed C until 49-56 days of age, and then transferred a HE diet for 3 weeks before allocation to one of two weight-matched groups. Over the next 10 weeks, one group remained on HE diet, whereas the other had access to the liquid diet, chocolate Ensure (EN), in addition to HE diet (HE + EN). Half the rats from each group were then killed, and the remainder were returned to C for 3 weeks. Supplementation of the HE diet with EN accelerated weight gain and increased daily energy intake, adipose tissue mass, and circulating leptin levels. Transferring animals back to C caused a decrease in bodyweight in the HE + EN group, whereas HE animals were weight stable. Both groups also exhibited voluntary hypophagia, although the magnitude and duration of this response was greater in HE + EN animals. The only effect of Ensure on the hypothalamic genes studied was on tyrosine kinase B expression in the ventromedial hypothalamic nucleus (VMH), which was increased in rats given the supplement. Withdrawal of the obesogenic diets decreased gene expression for cocaine-and-amphetamine regulated transcript (CART) and dynorphin (DYN) in the arcuate nucleus (ARC), and DYN and brain-derived neurotrophic factor (BDNF) in the VMH, whereas neuropeptide Y (NPY) gene expression in the ARC was increased. These changes were independent of previous dietary history. EN supplementation generates distinct physiological responses, yet has a minimal effect on hypothalamic neuropeptide or receptor gene expression, possibly due to the development of leptin resistance. Withdrawal of obesogenic diets induces changes in the gene expression consistent with NPY, CART and BDNF attempting to oppose weight gain on either HE or HE + EN.

Animals↗

PubMed2005

Effect of photoperiod on body mass, food intake and body composition in the field vole, Microtus agrestis.

Many small mammals respond to seasonal changes in photoperiod by altering body mass and adiposity. These animals may provide valuable models for understanding the regulation of energy balance. Here, we present data on the field vole (Microtus agrestis) - a previously uncharacterised example of photoperiod-induced changes in body mass. We examined the effect of increased day length on body mass, food intake, apparent digestive efficiency, body composition, de novo lipogenesis and fatty acid composition of adipose tissue in cold-acclimated (8 degrees C) male field voles by transferring them from a short (SD, 8 h:16 h L:D) to long day photoperiod (LD, 16 h:8 h L:D). During the first 4 weeks of exposure to LD, voles underwent a substantial increase in body mass, after which the average difference between body masses of LD and SD voles stabilized at 7.5 g. This 24.8% increase in body mass reflected significant increases in absolute amounts of all body components, including dry fat mass, dry lean mass and body water mass. After correcting body composition and organ morphology data for the differences in body mass, only gonads (testes and seminal vesicles) were enlarged due to photoperiod treatment. To meet energetic demands of deposition and maintenance of extra tissue, voles adjusted their food intake to an increasing body mass and improved their apparent digestive efficiency. Consequently, although mass-corrected food intake did not differ between the photoperiod groups, the LD voles undergoing body mass increase assimilated on average 8.4 kJ day(-1) more than animals maintained in SD. The majority (73-77%) of the fat accumulated as adipose tissue had dietary origin. The rate of de novo lipogenesis and fatty acid composition of adipose tissue were not affected by photoperiod. The most important characteristics of the photoperiodic regulation of energy balance in the field vole are the clear delineation between phases where animals regulate body mass at two different levels and the rate at which animals are able to switch between different levels of energy homeostasis. Our data indicate that the field vole may provide an attractive novel animal model for investigation of the regulation of body mass and energy homeostasis at both organism and molecular levels.

Adaptation, Physiological↗

PubMed2004

Circulating ghrelin levels and central ghrelin receptor expression are elevated in response to food deprivation in a seasonal mammal (Phodopus sungorus).

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHSR). However, the functional interaction of ligand and receptor is not very well understood. We demonstrate that GHSR mRNA is up-regulated after food deprivation (48 h) in the hypothalamic arcuate nucleus and ventromedial nucleus of the seasonal Siberian hamster, Phodopus sungorus. This increase is accompanied by a two-fold elevation of circulating ghrelin concentration. Chronic changes in feeding state imposed by food restriction over a period of 12 weeks during long day-length induced increased GHSR gene expression, whereas food restriction for 6 weeks had no effect. Phodopus sungorus reveals remarkable seasonal changes in body weight, fat mass and circulating leptin levels. Ghrelin is generally regarded as having opposing effects on appetite and body weight with respect to those exhibited by leptin. However, our study revealed that seasonal adaptations were not accompanied by changes in either GHSR gene expression or circulating ghrelin concentration. Therefore, we suggest that ghrelin only plays a minor role in modulating long-term seasonal body weight cycles. Our findings imply that ghrelin predominantly acts as a short-term regulator of feeding.

Adaptation, Physiological↗

PubMed2004

Increasing the impact of European obesity research in preparation for the European research area: a report on the 2003 European Commission Obesity Workshop.

Leading obesity researchers from across Europe assembled in Aberdeen, Scotland, in January 2003 to consider how to increase the impact of European obesity research. The workshop was funded by the European Commission and hosted by the Rowett Research Institute, Aberdeen. The delegates identified the need to (i) develop a portfolio of studies that integrate genetics and mechanisms through parallel study of humans and animal models and (ii) establish major intervention studies in weight management and early life nutrition. It was recommended that these goals would be best achieved under the umbrella of a virtual European Obesity Research Institute, or Network of Excellence in Obesity Research under Framework Programme 6, that would facilitate harmonization of methodology, manage centralized standardized resources, coordinate training initiatives, workshops and working groups, and increase focus.

Diet↗

PubMed2004

Photoperiodic effects on body mass, energy balance and hypothalamic gene expression in the bank vole.

We examined the effect of increasing photoperiod, at a constant low temperature, on the body mass and energy budget of the bank vole Clethrionomys glareolus. Simultaneously, we determined the hypothalamic gene expression of neuropeptides and receptors known to be involved in short-term energy balance. Despite an increase in body mass (approximately 10% of initial mass), we found no significant changes in any energetic parameters (food intake, energy assimilation rate, resting metabolic rate and total daily energy expenditure by doubly-labelled water). Apparent energy assimilation efficiency was higher in voles exposed to long-days (LD) compared to short-days (SD). Surprisingly, gene expression of corticotrophin releasing factor (CRF; in the paraventricular nucleus), and the melanocortin-3 receptor (in the arcuate nucleus), both known to be involved in appetite suppression and elevation of energy expenditure in short-term energy balance, were higher in voles kept in LD compared to SD. CRF expression was also elevated in females compared to males. These paradoxical data suggest an alternative mechanism for the control of seasonal body mass changes compared to short-term body mass changes, and between male and female voles. Furthermore, they highlight the need for studies to perform simultaneous measurements at both the molecular and whole animal levels.

Animals↗

PubMed2003

Precursor-protein convertase 1 gene expression in the mouse hypothalamus: differential regulation by ob gene mutation, energy deficit and administration of leptin, and coexpression with prepro-orexin.

The expression of precursor-protein convertase (PC)1, PC2 and paired basic amino acid cleaving enzyme four mRNA was studied by in situ hybridisation in regions of the hypothalamus involved in energy regulation in relation to obese (ob) gene mutation and energy deficit. PC1 gene was differentially expressed in hypothalamic nuclei of mice from different genetic backgrounds or energetic status, whereas no differences in expression were observed for either the PC2 or paired basic amino acid cleaving enzyme four genes. In obese ob/ob mice, PC1 mRNA levels were increased in the paraventricular nucleus, decreased in the lateral hypothalamus and unchanged in the ventromedial nucleus and arcuate nucleus relative to lean controls. In response to intraperitoneal injection of murine leptin, PC1 mRNA levels in obese ob/ob mice decreased in the arcuate nucleus, increased in the lateral hypothalamus and were unchanged in both the paraventricular nucleus and ventromedial nucleus. In mice deprived of food for 24 h, PC1 mRNA levels were reduced in the ventromedial nucleus, increased in the lateral hypothalamus and unchanged in the paraventricular nucleus and arcuate nucleus relative to ad libitum-fed controls. Overall, whilst the data show effects related to leptin and energetic status, they do not support a strong and consistent link between PC1 gene expression and energy balance. This suggests that if PC1 is important to the control of energy balance then protein expression and activity, rather than gene expression may be the more critical parameters of regulation. The relationship between PC1 and candidate energy balance-related genes in the lateral hypothalamus was investigated by dual in situ hybridisation. PC1 mRNA was localised in prepro-orexin mRNA expressing neurons in the lateral hypothalamus, which suggests a functional relationship.

Animals↗

PubMed2003

Neuromedin U and Neuromedin U receptor-2 expression in the mouse and rat hypothalamus: effects of nutritional status.

Neuromedin U (NMU) has been associated with the regulation of food-intake and energy balance in rats. The objective of this study was to identify the sites of gene expression for NMU and the NMU receptor-2 (NMU2R) in the mouse and rat hypothalamus and ascertain the effects of nutritional status on the expression of these genes. In situ hybridization studies revealed that NMU is expressed in several regions of the mouse hypothalamus associated with the regulation of energy balance. Analysis of NMU expression in the obese ob/ob mouse revealed that NMU mRNA levels were elevated in the dorsomedial hypothalamic (DMH) nucleus of obese ob/ob mice compared to lean litter-mates. In addition, NMU mRNA levels were elevated in the DMH of mice fasted for 24 h relative to ad libitum fed controls. The pattern of expression of NMU and NMU2R were more widespread in the hypothalamus of mice than rats. These data provide the first detailed anatomical analysis of the NMU and NMU2R expression in the mouse and advance our knowledge of expression in the rat. The data from the obese rodent models supports the hypothesis that NMU is involved in the regulation of nutritional status.

Animals↗

PubMed2003

Photoperiodic programming of body weight through the neuroendocrine hypothalamus.

The photoperiodic mammal undergoes quite remarkable changes in physiology as part of its natural adaptations to seasonal fluctuations in the environment. Changes in energy balance and body weight are among these adaptations. In some seasonal mammals, such as the Siberian hamster (Phodopus sungorus), these changes in body weight have been explored in detail, and there is evidence for tightly controlled systems of energy balance that are coordinated by photoperiod acting via the temporal pattern of melatonin secretion from the pineal gland. The pathways and systems involved appear to be quite distinct from the hypothalamic pathways identified to regulate energy balance in studies of both mice and rats thus far. Instead it appears that in the Siberian hamster a tightly regulated system under the control of photoperiod is able to reset the tone of the systems involved in energy balance regulation. Understanding how photoperiod and melatonin act within the hypothalamus to regulate energy balance offers potentially fundamental and important new insights into the control of energy balance. This review describes the current state of our knowledge.

Animals↗

PubMed2001

Hypothalamic neuropeptide mechanisms for regulating energy balance: from rodent models to human obesity.

In small rodents there is compelling evidence of a lipostatic system of body mass regulation in which peripheral signals of energy storage are decoded in the hypothalamus. The ability of small mammals to defend an appropriate mass against imposed energy imbalance has implicated hypothalamic neuroendocrine systems in body mass regulation. The effect of the neuropeptide systems involved in this regulation is primarily compensatory. However, small mammals can also effect changes in the level of body mass that they will defend, as exemplified by seasonal species. Regulatory control over fat mass may be relatively loose in humans; the sizes of long-term storage depots may not themselves be regulated, but rather may be a consequence of temporal variations in the matching of supply and demand. Whether food intake is regulated to match energy demand, or to match demand and to regulate storage, it is clear that physiological defects or genetic variation in hypothalamic and peripheral feedback systems will have profound implications for fat storage. Study of mechanisms implicated in energy homeostasis in laboratory rodents is likely to continue to identify targets for pharmacological manipulation in the management of human obesity.

Animals↗

PubMed2001

The differential regulation of CART gene expression in a pituitary cell line and primary cell cultures of ovine pars tuberalis cells.

The cocaine-amphetamine regulated transcript (CART) encodes for a protein which has an important role in the regulation of appetite and body weight. To date, no details of the molecular events and signal transduction pathways which regulate this gene are available. We report the identification of CART gene expression in the GH3 pituitary cell line. We have used activators of the cAMP or protein kinase C (PKC) signal transduction pathways to show that, in GH3 cells, CART is transcriptionally up-regulated by activators of the cAMP signal transduction pathway. We also identify CART gene expression in ovine pars tuberalis (PT) tissue and primary cell cultures. In PT cells in contrast to GH3 cells, CART gene expression is upregulated by activators of the PKC signal transduction pathway. Cultured cells have provided a valuable resource for the detailed analysis of specific regulatory mechanisms underlying transcriptional or translational regulation of genes, signal transduction events and many other cellular processes. GH3 and PT cells may therefore provide a resource for the further detailed molecular analysis of the events regulating CART gene expression and processing.

Animals↗

PubMed2001

Localization of the melatonin-related receptor in the rodent brain and peripheral tissues.

Previous studies have provided a limited examination of the expression of the orphan melatonin-related receptor in the pituitary and hypothalamus of human and sheep and retinal tissue in the sheep. The present study reports evidence of conservation of expression in regions of the hypothalamus (dorsal medial hypothalamus, lateral hypothalamus, arcuate nucleus), the epithelial layer lining the third ventricle and the paraventricular thalamic nucleus of the mouse, rat and hamster. An extensive and detailed analysis of melatonin-related receptor mRNA expression in the mouse central nervous system and peripheral tissues is presented. Mapping the distribution throughout the entire mouse brain has revealed new sites of expression in a number of brain nuclei, including preoptic areas, parabrachial nuclei and widespread distribution in the olfactory bulb. Reverse transcriptase-polymerase chain reaction was performed with RNA isolated from peripheral tissues revealing expression of the melatonin-related receptor mRNA in the mouse kidney, adrenal gland, intestine, stomach, heart, lung, skin, testis and ovary. These results suggest a conserved function in neuroendocrine regulation and a potential role in coordinating physiological responses in the central nervous system and peripheral tissues.

Animals↗