Recent Progress in Hormone Research 59:395-408 (2004)
© 2004 The Endocrine Society
The Central Melanocortin System and the Integration of Short- and Long-term Regulators of Energy Homeostasis
Kate L.J. Ellacott and
Roger D. Cone
Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239-3098
 |
ABSTRACT
|
|---|
The importance of the central melanocortin system in the regulation of energy balance is highlighted by studies in transgenic animals and humans with defects in this system. Mice that are engineered to be deficient for the melanocortin-4 receptor (MC4R) or pro-opiomelanocortin (POMC) and those that overexpress agouti or agouti-related protein (AgRP) all have a characteristic obese phenotype typified by hyperphagia, increased linear growth, and metabolic defects. Similar attributes are seen in humans with haploinsufficiency of the MC4R. The central melanocortin system modulates energy homeostasis through the actions of the agonist, 
-melanocyte-stimulating hormone (-MSH), a POMC cleavage product, and the endogenous antagonist AgRP on the MC3R and MC4R. POMC is expressed at only two locations in the brain: the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the tractus solitarius (NTS) of the brainstem. This chapter will discuss these two populations of POMC neurons and their contribution to energy homeostasis. We will examine the involvement of the central melanocortin system in the incorporation of information from the adipostatic hormone leptin and acute hunger and satiety factors such as peptide YY (PYY3–36) and ghrelin via a neuronal network involving POMC/cocaine and amphetamine-related transcript (CART) and neuropeptide Y (NPY)/AgRP neurons. We will discuss evidence for the existence of a similar network of neurons in the NTS and propose a model by which this information from the ARC and NTS centers may be integrated directly or via adipostatic centers such as the paraventricular nucleus of the hypothalamus (PVH).
|
I. Introduction
|
|---|
Pro-opiomelanocortin (POMC) modulates energy homeostasis principally through one of its cleavage products, -melanocyte-stimulating hormone (-MSH), which exerts a tonic inhibitory control on food intake and energy storage though its actions in the central nervous system (CNS) at two of the five known melanocortin receptors, melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) (for a review, see Cone, 1999). While the contribution of the agonist -MSH is important, it is the endogenous antagonist at these receptors, agouti-related protein (AgRP) (Ollmann et al., 1997), whose mRNA shows a greater degree of regulation by extremes of negative or positive energy balance such as fasting and diet-induced obesity in rodents (Mizuno and Mobbs, 1999; Ziotopoulou et al., 2000). The most-compelling evidence, however, for a pivotal role for the central melanocortin system in the regulation of energy homeostasis comes from studies in transgenic mice (for a review, see Butler and Cone, 2001). POMC and MC4R knockout mice and mice that overexpress the agouti gene (Ay/a) or AgRP all have a characteristic obese phenotype typified by hyperphagia, increased linear growth, and metabolic defects (Yen et al., 1994; Huszar et al., 1997; Ollmann et al., 1997; Yaswen et al., 1999). Similar attributes are seen in humans with mutations in genes of the central melanocortin system. Defects in the MC4R gene have been linked to obesity, particularly severe early-onset obesity in children (Farooqi et al., 2000). Significantly, alterations in this gene have been linked to up to 5% of cases in children and adults (Farooqi et al., 2003).
Although there are five melanocortin receptors, it is the MC3R and MC4R subtypes that have been implicated in the regulation of energy balance (for a review, see Adan et al., 1997). While these receptors both have a fairly widespread distribution in the rodent brain (Roselli-Rehfuss et al., 1993; Mountjoy et al., 1994; Kishi et al., 2003), POMC has a limited distribution, with only two neuronal populations described: one in the arcuate nucleus of the hypothalamus (ARC) and the other in the nucleus of the tractus solitarius (NTS) of the brainstem (Joseph et al., 1983; Palkovits et al., 1987; Bronstein et al., 1992). Of these two populations, the ARC neurons have drawn the most attention from researchers. The ARC and other hypothalamic nuclei have classically been associated with the actions of leptin and the regulation of body weight in the long term, while the NTS and other brainstem nuclei predominantly are linked to the regulation of meal initiation and termination (Grill and Kaplan, 2002). We will review evidence for the involvement of both populations of POMC neurons in the regulation of energy homeostasis, both in the long term and short term, and discuss the potential for the integration of information from these two sites by adipostatic centers.
|
II. POMC Neurons and the ARC Neuronal Network
|
|---|
A. THE ARC NEURONAL NETWORK AND LONG-TERM REGULATORS OF ENERGY HOMEOSTASIS
The POMC neurons of the ARC are known to be responsive to leptin via leptin receptors (Ob-R) expressed on their surface (Cheung et al., 1997). In addition to the POMC neurons, another important element of the melanocortin system in the hypothalamus is the neurons that express the melanocortin receptor antagonist AgRP, which also express the orexigenic peptide, neuropeptide Y (NPY) (Hahn et al., 1998) and are leptin sensitive (Wilson et al., 1999). These NPY/AgRP-containing neurons are able to form synapses with POMC neurons of the ARC and exert regulatory effects, producing a neuronal network that is responsive to the modulatory actions of leptin (Figure 1) (Cowley et al., 2001). In this model, leptin causes hyperpolarization of NPY/AgRP neurons, leading to a reduction in the release of gamma aminobutyric acid (GABA) that, in turn, causes disinhibition of the POMC neurons with which they synapse. In addition to its indirect actions on the POMC neurons via NPY/AgRP cells, leptin appears to act on the POMC system directly by causing a depolarization of the ARC neurons, increasing their firing rate. This model demonstrates how leptin may serve as an overall modulator of energy homeostasis by altering the firing rate of orexigenic and anorexigenic neurons. The fact that serum leptin levels do not vary after meals (Korbonits et al., 1997) but generally are proportional to adipose mass (Maffei et al., 1995) suggests that leptin is not acting as an anorectic factor but rather as an indicator of the long-term energy status of the animal. Thus, modulation of the firing rate of neurons of the ARC and other hypothalamic sites may be a means by which the body weight of an animal is maintained and adjusted over extended periods of time in response to variations in leptin levels.
View larger version (47K):
[in this window]
[in a new window]
|
FIG. 1. The arcuate nucleus (ARC) neuronal network. Neuropeptide Y/agouti-related protein (NPY/AgRP) neurons form synapses with the pro-opiomelanocortin/cocaine and amphetamine-regulated transcript (POMC/CART) neurons in the ARC, forming a regulatory network that is responsive to leptin via leptin receptors (Ob-R) present on their surface. Leptin acts on POMC neurons directly and indirectly via a reduction in the release of gamma aminobutyric acid (GABA) from NPY/AgRP neurons. The circuit is able to respond, via growth hormone secretagogue receptor (GHS-R) and Y2-R, to signals from ghrelin and PYY3–36.
|
|
B. THE MELANOCORTIN SYSTEM AND SHORT-TERM REGULATORS OF ENERGY HOMEOSTASIS
In addition to the mediation of long-term changes in energy balance via signals from leptin, we have shown that POMC neurons of the ARC may be able to respond to signals from the gut hormone peptide YY3–36 (PYY3–36) (Batterham et al., 2002). PYY3–36, an N-terminal truncated form of PYY, is released from the lower intestine following a meal in proportion to the number of calories ingested (Pedersen-Bjergaard et al., 1996). ARC POMC neurons are activated by administration of PYY3–36 via Y2 receptors (Y2-R) on NPY/AgRP neurons that, in turn, causes modulation of the hypothalamic ARC network previously described. This evidence suggests that the ARC network actually may integrate information from both long-term signals of nutritional status and satiety signals that are released postprandially from the gut. While the finding that direct injection of PYY3–36 into the ARC causes a reduction in food intake, it remains to be established whether the ARC is the functional site of action of PYY3–36 in vivo or whether, in common with other postprandially released gastric peptides, it acts via the brainstem and sites in the gut itself. In addition to PYY3–36, there is evidence to suggest that the network may be activated by other gut hormones. The satiety signal cholecystokinin (CCK) has been shown to electrically (Burdakov and Ashcroft, 2002) modulate the activity of ARC neurons, although these have not been identified as containing POMC or NPY/AgRP. This indicates that there is potential for an interaction between the central melanocortin system and other postprandially released gut peptides.
Another more-recently identified gut-derived peptide is ghrelin. Ghrelin is the endogenous peptide for the growth hormone secretagogue receptor (GHS-R), the mRNA for which is expressed in a number of sites in the hypothalamus (Guan et al., 1997). Ghrelin originally was described as being produced by the oxyntic cells of the stomach (Kojima et al., 1999) but since has been shown to be expressed at low levels in the small intestine (Date et al., 2000), kidney (Mori et al., 2000), testis (Tanaka et al., 2001), placenta (Gualillo et al., 2001), brain (Lu et al., 2002; Cowley et al., 2003), lymphocytes (Hattori et al., 2001), pituitary (Korbonits et al., 2001), and pancreas (Volante et al., 2002). Perhaps unsurprisingly, due to the close association between growth and energy homeostasis and what was already known about the effects of synthetic growth hormone secretagogue (Bercu et al., 1992), ghrelin peptide and mRNA levels were shown to be regulated by changes in energy balance such as fasting (Tschop et al., 2000; Cummings et al., 2001), hypoglycemia (Toshinai et al., 2001), and diet-induced obesity (Tschop et al., 2000) in rodents. However, the effects of ghrelin are independent of GH secretion (Tschop et al., 2000; Wren et al., 2000; Nakazato et al., 2001).
NPY/AgRP neurons of the ARC have been implicated in mediating ghrelin’s effects on energy homeostasis (Kamegai et al., 2001; Nakazato et al., 2001; Shintani et al., 2001; Lawrence et al., 2002b; Wang et al., 2002). Ghrelin has a unique distribution in the brain, encompassing the internuclear space between the ARC, ventromedial (VMH), dorsomedial (DMH), and paraventricular hypothalamic nuclei (PVH) (Cowley et al., 2003). The discovery of this network led to questions about whether the effects of ghrelin on the ARC NPY/AgRP neurons were due to centrally or peripherally derived ghrelin, or both. Indeed, axons from ghrelin-containing neurons form synaptic contact with NPY/AgRP and POMC neurons of the ARC (Cowley et al., 2003). Electrical recording from these ARC neurons indicates that ghrelin is able to cause depolarization of ARC NPY/AgRP neurons and hyperpolarization of POMC neurons. When considered in conjunction with studies showing that c-fos is activated in NPY/AgRP but not in POMC neurons following peripheral ghrelin administration (Wang et al., 2002), the data would suggest that the effect of ghrelin on POMC neurons is probably inhibitory, mediated by the action of GABA released by NPY/AgRP neurons (Cowley et al., 2003).
In the same study, it was demonstrated that in addition to its effects in the ARC, ghrelin is able to influence the activity of PVH corticotropin-releasing hormone (CRH) neurons, possibly via an increase in release of GABA from NPY/AgRP neurons, in a similar manner to its effects on POMC neurons. The interaction between the ARC neuronal network and the neurons of the PVH will be discussed further in this review. In addition to interacting with NPY and the central melanocortin system, evidence suggests that ghrelin interacts with the orexigenic peptide orexin/hypocretin in the brain. Central administration of ghrelin in rats causes activation of orexin-containing neurons of the lateral hypothalamic area (LHA) (Lawrence et al., 2002b). Ghrelin-immunoreactive terminals make contact with orexin neurons in the LHA (Toshinai et al., 2003). The blockade of orexin-A and -B receptors by injection of antisera attenuates the effects of centrally administered ghrelin on food intake, providing in vivo evidence for an interaction between the two peptides. The wide distribution of ghrelin-immunoreactive neurons (Cowley et al., 2003), GHS-R mRNA (Guan et al., 1997), and the data outlined earlier suggest that, in common with leptin, ghrelin may serve as an overall modulator of a number of anorexigenic and orexigenic pathways directly and via the ARC neuronal network.
|
III. POMC Neurons of the NTS
|
|---|
A. THE INVOLVEMENT OF NTS POMC NEURONS IN THE REGULATION OF FOOD INTAKE
In recent years, while most of the attention in the field of energy homeostasis has been concentrated on the hypothalamus, the importance of the brainstem largely has been neglected. As such, comparatively little is known about the POMC neurons of the brainstem. An extensive network of fibers immunoreactive for POMC-derived peptides exists in the brainstem. This network includes immunoreactivity in the NTS, lateral reticular nucleus (A5-C1 groups), ventrolateral medulla (A1 cell group), and nucleus ambiguus. The only POMC cell bodies present in the brainstem are found in the commissural region of the NTS. Interestingly, POMC neurons have been shown to send a number of projections within the brainstem, particularly to the ventral lateral medulla and onto the spinal cord. However, studies involving lesioning of hypothalamic connections indicate that only 30–50% of the POMC-derived immunoreactivity in the brainstem originates from cell bodies in the commissural NTS (Palkovits et al., 1987; Joseph and Michael, 1988). The remainder of the immunoreactivity seen is derived from projections from the hypothalamic POMC neurons. Hypothalamic POMC fibers innervate the brainstem via two distinct pathways: one that travels via the periaqueductal gray and the dorsomedial tegmentum to innervate the rostral NTS and lateral reticular nucleus (A5-C1 groups) and a second, more-dominant pathway through the ventrolateral tegmentum, believed to be the route of the majority of descending pathways, that innervates the rostral NTS, ventrolateral medulla (A1 cell group), nucleus ambiguus, and the descending spinal bundle. The MC4R is expressed at a number of these sites, indicating that hypothalamic POMC may exert some of its effects on energy homeostasis via receptors in the brainstem (Kishi et al., 2003).
The work of Grill and colleagues has demonstrated that the melanocortin system of the brainstem plays a role in regulation of energy homeostasis. Administration of MTII, a synthetic melanocortin receptor agonist, or SHU9119, an MC3R and MC4R antagonist, into the fourth ventricle or directly into the dorsal vagal complex (DMX) causes a reduction in food intake in the case of MTII and an increase in food intake in the case of SHU9119 (Williams et al., 2000). Following fourth ventricular administration, changes seen are comparable with those following administration of MTII or SHU9119 into the lateral ventricle (Grill et al., 1998).
A potentially important consideration when studying the melanocortin system of the brainstem is the low level of expression of the endogenous antagonist AgRP. In contrast to the hypothalamus, where there is a relatively high level of expression of both the AgRP- and POMC-immunoreactive fibers and terminals that project to identical areas of the brain (Bagnol et al., 1999), the brainstem has few, if any, AgRP-immunoreactive cell bodies and receives limited terminals from the ARC. Given the lack of AgRP in the brainstem, it is unknown what regulates melanocortinergic tone in this area. It is unlikely that much regulation comes from AgRP projections from the hypothalamus but it is feasible that the system in this area is regulated by other mechanisms such as differences in POMC processing or post-translational modification (for a review of POMC processing, see Pritchard et al., 2002).
B. EVIDENCE FOR THE EXISTENCE OF A REGULATORY NEURONAL NETWORK IN THE BRAINSTEM: COMPARISON WITH THE ARC NEURONAL NETWORK
Taking into account all the evidence to suggest the existence of a POMC-NPY/AgRP neuronal network in the ARC, it is interesting to speculate whether a similar network may be involved in modulating energy homeostasis via the brainstem. While the ARC network is able to respond to what are considered long-term as well as short-term modulators of energy homeostasis, is there any reason that a similar network should not exist in the NTS?
A number of similarities between the ARC and the NTS make the existence of such a network possible. First, they both lie in close anatomical proximity to a circumventricular organ, the median eminence in the case of the ARC and the area postrema in the case of the NTS. Although AgRP cell bodies are absent, the NTS contains cell bodies that show immunoreactivity for NPY and POMC-derived peptides. In common with the ARC, the NTS contains leptin receptors (Hakansson et al., 1998; Mercer et al., 1998). These neurons have been shown to be able to mediate the inhibitory effects of leptin on food intake and body weight gain following fourth ventricle administration (Grill et al., 2002). In addition to causing activation of hypothalamic sites, peripheral administration of leptin activates neurons of the NTS, as measured by the expression of signal transducer and activator of transcription (STAT)-3 (Hosoi et al., 2002; Munzberg et al., 2003) or c-fos (Elmquist et al., 1997). The NTS receives projections from numerous centers in the brain but is also the site at which vagal afferents terminate, making it an important site in mediating the vago-vagal reflex.
|
IV. The PVH as a Site of Integration of Hypothalamic and Brainstem Signals
|
|---|
The PVH is an important hypothalamic nucleus in the integration of autonomic and neuroendocrine information (for a review, see Palkovits, 1999). The PVH receives projections from a number of sites in the brain, including the ARC and NTS (Sawchenko and Swanson, 1983). Both melanocortin and NPY/AgRP terminals are present in this area (Bagnol et al., 1999). Indeed, NTS NPY neurons have been shown to project to the PVH (Sawchenko et al., 1985). The PVH may serve as a site of integration of information from melanocortin, NPY/AgRP, and possibly other orexigenic and anorexigenic neurons via GABAergic interneurons. Evidence for this model comes from in vivo and electrophysiological studies. Direct injection of the melanocortin agonist MTII into the PVH results in a reduction in food intake. MTII at this site is able to functionally antagonize the orexigenic effects of NPY, indicating the potential for interactions between the two systems in the PVH in vivo. Electrophysiological studies have shown that neurons expressing NPY/AgRP and POMC have opposing actions on neurons of the medial PVH, potentiating and inhibiting GABAergic currents, respectively (Cowley et al., 1999). Modulation of the central melanocortin system following intracerebroventricular administration of MTII, -MSH, or AgRP activates a number of hypothalamic and extrahypothalamic sites in rats, including in the PVH (Thiele et al., 1998; McMinn et al., 2000; Hagan et al., 2001). Indeed, the PVH seems to be a site that is activated following administration of a number of orexigenic and anorexigenic peptides, reinforcing the hypothesis that it is a key site for the integration of information regarding energy homeostasis (Hamamura et al., 1991; Lambert et al., 1995; Van Dijk et al., 1996; Elmquist et al., 1997; Edwards et al., 1999; Lawrence et al., 2002a).
The ARC melanocortin and NPY neurons innervate neurosecretory neurons of both the parvocellular and magnocellular subdivisions of the PVH (Piekut, 1985,1987; Liposits et al., 1988; Sawchenko and Pfeiffer, 1988; Li et al., 2000). The innervation of the thyrotrophin-releasing hormone (TRH) neurons has been particularly well characterized. Neurons containing immunoreactivity for both AgRP and NPY or -MSH innervate TRH neurons in the PVH directly through projections from the ARC and indirectly via projections from the medial preoptic nucleus (Legradi and Lechen, 1999; Fekete et al., 2000; Kawano and Masuko, 2000). These and numerous other anatomical studies highlight the importance of the PVH as a site for the integration of information from a number of systems and demonstrate how the regulation of energy balance may modulate other neuroendocrine processes such as the growth, reproductive, and stress axes (Schioth and Watanobe, 2002; Smith and Grove, 2002).
As discussed earlier, in addition to the PVH acting as a site of integration, the neurons of the ARC and NTS may communicate via direct projections between the two sites. ARC POMC neurons have been shown to project to a number of sites in the brainstem, including the NTS, periaqueductal gray, dorsal raphe nucleus, nucleus raphe magnus, nucleus raphe pallidus, locus coeruleus, parabrachial nucleus, nucleus reticularis gigantocellularis, and DMX (Chronwall, 1985; Sim and Joseph, 1991). Many of these regions contain MC4R mRNA (Mountjoy et al., 1994; Kishi et al., 2003), raising the possibility that these receptors in the brainstem may be served by projections from the ARC neurons in addition to or in place of projections from the POMC neurons of NTS.
|
V. Summary
|
|---|
The evidence presented herein reinforces the importance of the POMC-NPY/AgRP system in the regulation of energy homeostasis and a number of other neuroendocrine processes. Localization of the POMC-NPY/AgRP neuronal networks in the ARC and possibly the NTS and the diversity of their neuronal projections from these sites make them well placed to respond to and coordinate both long-term adipostatic and short-term hunger/satiety signals between the periphery and the brain.
|
ACKNOWLEDGEMENTS
|
|---|
We would like to thank the Wellcome Trust and the National Institutes of Health for financial support.
|
REFERENCES
|
|---|
Adan RA, Oosterom J, Toonen RF, Kraan MV, Burbach JP, Gispen WH 1997
Molecular pharmacology of neural melanocortin receptors. Receptors Channels
5(3–4)
: 215
–223
Bagnol D, Lu XY, Kaelin CB, Day HE, Ollmann M, Gantz I, Akil H, Barsh GS, Watson SJ 1999
Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J Neurosci
19
(18): RC26
Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR 2002
Gut hormone PYY(3–36) physiologically inhibits food intake. Nature
418
(6898): 650
–654[CrossRef][Medline]
Bercu BB, Yang SW, Masuda R, Hu CS, Walker RF 1992
Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats. Endocrinology
131
(6): 2800
–2804[Abstract]
Bronstein DM, Schafer MK, Watson SJ, Akil H 1992
Evidence that beta-endorphin is synthesized in cells in the nucleus tractus solitarius: detection of POMC mRNA. Brain Res
587
(2): 269
–275[CrossRef][Medline]
Burdakov D, Ashcroft FM 2002
Cholecystokinin tunes firing of an electrically distinct subset of arcuate nucleus neurons by activating A-type potassium channels. J Neurosci
22
(15): 6380
–6387[Abstract/Free Full Text]
Butler AA, Cone RD 2001
Knockout models resulting in the development of obesity. Trends Genet
17
(10): S50
–S54[CrossRef][Medline]
Chronwall BM 1985
Anatomy and physiology of the neuroendocrine arcuate nucleus. Peptides
6(suppl 2)
: 1
–11
Cheung CC, Clifton DK, Steiner RA 1997
Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology
138
(10): 4489
–4492[Abstract/Free Full Text]
Cone RD 1999
The central melanocortin system and energy homeostasis. Trends Endocrinol Metab
10
(6): 211
–216[CrossRef][Medline]
Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD 1999
Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron
24
(1): 155
–163[CrossRef][Medline]
Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, Cone RD, Low MJ 2001
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature
411
(6836): 480
–484[CrossRef][Medline]
Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL 2003
The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron
37
(4): 649
–661[CrossRef][Medline]
Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS 2001
A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes
50
(8): 1714
–1719[Abstract/Free Full Text]
Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M 2000
Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology
141
(11): 4255
–4261[Abstract/Free Full Text]
Edwards CM, Abusnana S, Sunter D, Murphy KG, Ghatei MA, Bloom SR 1999
The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin. J Endocrinol
160
(3): R7
–R12[Abstract]
Elmquist JK, Ahima RS, Maratos-Flier E, Flier JS, Saper CB 1997
Leptin activates neurons in ventrobasal hypothalamus and brainstem. Endocrinology
138
(2): 839
–842[Abstract/Free Full Text]
Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G, Cheetham T, O’Rahilly S 2000
Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest
106
(2): 271
–279[Medline]
Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O’Rahilly S 2003
Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med
348
(12): 1085
–1095[Abstract/Free Full Text]
Fekete C, Legradi G, Mihaly E, Huang QH, Tatro JB, Rand WM, Emerson CH, Lechan RM 2000
alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J Neurosci
20
(4): 1550
–1558[Abstract/Free Full Text]
Grill HJ, Kaplan JM 2002
The neuroanatomical axis for control of energy balance. Front Neuroendocrinol
23
(1): 2
–40[CrossRef][Medline]
Grill HJ, Ginsberg AB, Seeley RJ, Kaplan JM 1998
Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight. J Neurosci
18
(23): 10128
–10135[Abstract/Free Full Text]
Grill HJ, Schwartz MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG 2002
Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology
143
(1): 239
–246[Abstract/Free Full Text]
Gualillo O, Caminos J, Blanco M, Garcia-Caballero T, Kojima M, Kangawa K, Dieguez C, Casanueva F 2001
Ghrelin, a novel placental-derived hormone. Endocrinology
142
(2): 788
–794[Abstract/Free Full Text]
Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD 1997
Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res
48
(1): 23
–29[Medline]
Hagan MM, Benoit SC, Rushing PA, Pritchard LM, Woods SC, Seeley RJ 2001
Immediate and prolonged patterns of Agouti-related peptide-(83–132)-induced c-Fos activation in hypothalamic and extrahypothalamic sites. Endocrinology
142
(3): 1050
–1056[Abstract/Free Full Text]
Hahn TM, Breininger JF, Baskin DG, Schwartz MW 1998
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nature Neurosci
1
(4): 271
–272[CrossRef][Medline]
Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B 1998
Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci
18
(1): 559
–572[Abstract/Free Full Text]
Hamamura M, Leng G, Emson PC, Kiyama H 1991
Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin. J Physiol.
444
: 51
–63[Abstract/Free Full Text]
Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, Inagaki C 2001
GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab
86
(9): 4284
–4291[Abstract/Free Full Text]
Hosoi T, Kawagishi T, Okuma Y, Tanaka J, Nomura Y 2002
Brain stem is a direct target for leptin’s action in the central nervous system. Endocrinology
143
(9): 3498
–3504[Abstract/Free Full Text]
Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F 1997
Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell
88
(1): 131
–141[CrossRef][Medline]
Joseph SA, Michael GJ 1988
Efferent ACTH-IR opiocortin projections from nucleus tractus solitarius: a hypothalamic deafferentation study. Peptides
9
(1): 193
–201[Medline]
Joseph SA, Pilcher WH, Bennett-Clarke C 1983
Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system. Neurosci Lett
38
(3): 221
–225[CrossRef][Medline]
Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I 2001
Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes
50
(11): 2438
–2443[Abstract/Free Full Text]
Kawano H, Masuko S 2000
Beta-endorphin-, adrenocorticotrophic hormone- and neuropeptide Y-containing projection fibers from the arcuate hypothalamic nucleus make synaptic contacts on to nucleus preopticus medianus neurons projecting to the paraventricular hypothalamic nucleus in the rat. Neuroscience
98
(3): 555
–565[CrossRef][Medline]
Kishi T, Aschkenasi CJ, Lee CE, Mountjoy KG, Saper CB, Elmquist JK 2003
Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol
457
(3): 213
–235[CrossRef][Medline]
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K 1999
Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature
402
(6762): 656
–660[CrossRef][Medline]
Korbonits M, Trainer PJ, Little JA, Edwards R, Kopelman PG, Besser GM, Svec F, Grossman AB 1997
Leptin levels do not change acutely with food administration in normal or obese subjects, but are negatively correlated with pituitary-adrenal activity. Clin Endocrinol (Oxf)
46
(6): 751
–757[CrossRef][Medline]
Korbonits M, Bustin SA, Kojima M, Jordan S, Adams EF, Lowe DG, Kangawa K, Grossman AB 2001
The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab
86
(2): 881
–887[Abstract/Free Full Text]
Lambert PD, Phillips PJ, Wilding JP, Bloom SR, Herbert J 1995
c-fos expression in the paraventricular nucleus of the hypothalamus following intracerebroventricular infusions of neuropeptide Y. Brain Res
670
(1): 59
–65[CrossRef][Medline]
Lawrence CB, Ellacott KL, Luckman SM 2002
a PRL-releasing peptide reduces food intake and may mediate satiety signaling. Endocrinology
143
(2): 360
–367[Abstract/Free Full Text]
Lawrence CB, Snape AC, Baudoin FM, Luckman SM 2002
b Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology
143
(1): 155
–162[Abstract/Free Full Text]
Legradi G, Lechan RM 1999
Agouti-related protein containing nerve terminals innervate thyrotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. Endocrinology
140
(8): 3643
–3652[Abstract/Free Full Text]
Li C, Chen P, Smith MS 2000
Corticotropin releasing hormone neurons in the paraventricular nucleus are direct targets for neuropeptide Y neurons in the arcuate nucleus: an anterograde tracing study. Brain Res
854(1–2)
: 122
–129
Liposits Z, Sievers L, Paull WK 1988
Neuropeptide-Y and ACTH-immunoreactive innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamus of the rat. An immunocytochemical analysis at the light and electron microscopic levels. Histochemistry
88(3–6)
: 227
–234
Lu S, Guan JL, Wang QP, Uehara K, Yamada S, Goto N, Date Y, Nakazato M, Kojima M, Kangawa K, Shioda S 2002
Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci Lett
321
(3): 157
–160[CrossRef][Medline]
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S,et al. 1995
Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Med
1
(11): 1155
–1161[CrossRef][Medline]
McMinn JE, Wilkinson CW, Havel PJ, Woods SC, Schwartz MW 2000
Effect of intracerebroventricular alpha-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression. Am J Physiol Regul Integr Comp Physiol
279
(2): R695
–R703[Abstract/Free Full Text]
Mercer JG, Moar KM, Hoggard N 1998
Localization of leptin receptor (Ob-R) messenger ribonucleic acid in the rodent hindbrain. Endocrinology
139
(1): 29
–34[Abstract/Free Full Text]
Mizuno TM, Mobbs CV 1999
Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology
140
(2): 814
–817[Abstract/Free Full Text]
Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K 2000
Kidney produces a novel acylated peptide, ghrelin. FEBS Lett
486
(3): 213
–216[CrossRef][Medline]
Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD 1994
Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol
8
(10): 1298
–1308[Abstract]
Munzberg H, Huo L, Nillni EA, Hollenberg AN, Bjorbaek C 2003
Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin. Endocrinology
144
(5): 2121
–2131[Abstract/Free Full Text]
Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S 2001
A role for ghrelin in the central regulation of feeding. Nature
409
(6817): 194
–198[CrossRef][Medline]
Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS 1997
Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science
278
(5335): 135
–138[Abstract/Free Full Text]
Palkovits M 1999
Interconnections between the neuroendocrine hypothalamus and the central autonomic system. Geoffrey Harris Memorial Lecture, Kitakyushu, Japan, October 1998. Front Neuroendocrinol
20
(4): 270
–295[CrossRef][Medline]
Palkovits M, Mezey E, Eskay RL 1987
Pro-opiomelanocortin-derived peptides (ACTH/beta-endorphin/alpha-MSH) in brainstem baroreceptor areas of the rat. Brain Res
436
(2): 323
–338[CrossRef][Medline]
Pedersen-Bjergaard U, Host U, Kelbaek H, Schifter S, Rehfeld JF, Faber J, Christensen NJ 1996
Influence of meal composition on postprandial peripheral plasma concentrations of vasoactive peptides in man. Scand J Clin Lab Invest
56
(6): 497
–503[Medline]
Piekut DT 1985
Relationship of ACTH1–39-immunostained fibers and magnocellular neurons in the paraventricular nucleus of rat hypothalamus. Peptides
6
(5): 883
–990[CrossRef][Medline]
Piekut DT 1987
Interactions of immunostained ACTH1–39 fibers and CRF neurons in the paraventricular nucleus of rat hypothalamus: application of avidin-glucose oxidase to dual immunostaining procedures. J Histochem Cytochem
35
(2): 261
–265[Abstract]
Pritchard LE, Turnbull AV, White A 2002
Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol
172
(3): 411
–421[Abstract]
Roselli-Rehfuss L, Mountjoy KG, Robbins LS, Mortrud MT, Low MJ, Tatro JB, Entwistle ML, Simerly RB, Cone RD 1993
Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci USA
90
(19): 8856
–8860[Abstract/Free Full Text]
Sawchenko PE, Pfeiffer SW 1988
Ultrastructural localization of neuropeptide Y and galanin immunoreactivity in the paraventricular nucleus of the hypothalamus in the rat. Brain Res
474
(2): 231
–245[CrossRef][Medline]
Sawchenko PE, Swanson LW 1983
The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog Brain Res
60
: 19
–29[Medline]
Sawchenko PE, Swanson LW, Grzanna R, Howe PR, Bloom SR, Polak JM 1985
Colocalization of neuropeptide Y immunoreactvity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol
241
(2): 138
–153[CrossRef][Medline]
Schioth HB, Watanobe H 2002
Melanocortins and reproduction. Brain Res Rev
38
(3): 340
–350[CrossRef][Medline]
Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K 2001
Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes
50
(2): 227
–232[Abstract/Free Full Text]
Sim LJ, Joseph SA 1991
Arcuate nucleus projections to brainstem regions which modulate nociception. J Chem Neuroanat
4
(2): 97
–109[CrossRef][Medline]
Smith MS, Grove KL 2002
Integration of the regulation of reproductive function and energy balance: lactation as a model. Front Neuroendocrinol
23
(3): 225
–256[CrossRef][Medline]
Tanaka M, Hayashida Y, Nakao N, Nakai N, Nakashima K 2001
Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse. Biochim Biophys Acta
1522
(1): 62
–65[Medline]
Thiele TE, van Dijk G, Yagaloff KA, Fisher SL, Schwartz M, Burn P, Seeley RJ 1998
Central infusion of melanocortin agonist MTII in rats: assessment of c-Fos expression and taste aversion. Am J Physiol
274(1 Pt 2)
: R248
–R254
Toshinai K, Mondal MS, Nakazato M, Date Y, Murakami N, Kojima M, Kangawa K, Matsukura S 2001
Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun
281
(5): 1220
–1225[CrossRef][Medline]
Toshinai K, Date Y, Murakami N, Shimada M, Mondal MS, Shimbara T, Guan JL, Wang QP, Funahashi H, Sakurai T, Shioda S, Matsukura S, Kangawa K, Nakazato M 2003
Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology
144
(4): 1506
–1512[Abstract/Free Full Text]
Tschop M, Smiley DL, Heiman ML 2000
Ghrelin induces adiposity in rodents. Nature
407
(6806): 908
–913[CrossRef][Medline]
Van Dijk G, Thiele TE, Donahey JC, Campfield LA, Smith FJ, Burn P, Bernstein IL, Woods SC, Seeley RJ. 1996
Central infusions of leptin and GLP-1-(7–36) amide differentially stimulate c-FLI in the rat brain. Am J Physiol
271(4 Pt 2)
: R1096
–R1100
Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M 2002
Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab
87
(3): 1300
–1308[Abstract/Free Full Text]
Wang L, Saint-Pierre DH, Tache Y 2002
Peripheral ghrelin selectively increases Fos expression in neuropeptide Y-synthesizing neurons in mouse hypothalamic arcuate nucleus. Neurosci Lett
325
(1): 47
–51[CrossRef][Medline]
Williams DL, Kaplan JM, Grill HJ 2000
The role of the dorsal vagal complex and the vagus nerve in feeding effects of melanocortin-3/4 receptor stimulation. Endocrinology
141
(4): 1332
–1337[Abstract/Free Full Text]
Wilson BD, Bagnol D, Kaelin CB, Ollmann MM, Gantz I, Watson SJ, Barsh GS 1999
Physiological and anatomical circuitry between Agouti-related protein and leptin signaling. Endocrinology
140
(5): 2387
–2397[Abstract/Free Full Text]
Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR 2000
The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology
141
(11): 4325
–4328[Abstract/Free Full Text]
Yaswen L, Diehl N, Brennan MB, Hochgeschwender U 1999
Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nature Med
5
(9): 1066
–1070[CrossRef][Medline]
Yen TT, Gill AM, Frigeri LG, Barsh GS, Wolff GL 1994
Obesity, diabetes, and neoplasia in yellow A(vy)/- mice: ectopic expression of the agouti gene. FASEB J
8
(8): 479
–488[Abstract]
Ziotopoulou M, Mantzoros CS, Hileman SM, Flier JS 2000
Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice. Am J Physiol Endocrinol Metab
279
(4): E838
–E845[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
C. K. Song, C. H. Vaughan, E. Keen-Rhinehart, R. B. S. Harris, D. Richard, and T. J. Bartness
Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence
Am J Physiol Regulatory Integrative Comp Physiol,
August 1, 2008;
295(2):
R417 - R428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Bartness and C. K. Song
Thematic review series: Adipocyte Biology. Sympathetic and sensory innervation of white adipose tissue
J. Lipid Res.,
August 1, 2007;
48(8):
1655 - 1672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Li, Y. Zhang, E. Rodrigues, D. Zheng, M. Matheny, K.-Y. Cheng, and P. J. Scarpace
Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss
Am J Physiol Endocrinol Metab,
July 1, 2007;
293(1):
E252 - E258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-C. Peter, J. R. Nicholson, D. Heydet, A.-C. Lecourt, J. Hoebeke, and K. G. Hofbauer
Antibodies against the melanocortin-4 receptor act as inverse agonists in vitro and in vivo
Am J Physiol Regulatory Integrative Comp Physiol,
June 1, 2007;
292(6):
R2151 - R2158.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-H. Tai, W.-T. Weng, W.-C. Lo, J. Y. H. Chan, C.-J. Lin, H.-C. Lam, and C.-J. Tseng
Role of Nitric Oxide in {alpha}-Melanocyte-Stimulating Hormone-Induced Hypotension in the Nucleus Tractus Solitarii of the Spontaneously Hypertensive Rats
J. Pharmacol. Exp. Ther.,
May 1, 2007;
321(2):
455 - 461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. de Lartigue, R. Dimaline, A. Varro, and G. J. Dockray
Cocaine- and Amphetamine-Regulated Transcript: Stimulation of Expression in Rat Vagal Afferent Neurons by Cholecystokinin and Suppression by Ghrelin
J. Neurosci.,
March 14, 2007;
27(11):
2876 - 2882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Getting, C. W. Lam, G. Leoni, F. N. E. Gavins, P. Grieco, and M. Perretti
[D-Trp8]-{gamma}-Melanocyte-Stimulating Hormone Exhibits Anti-Inflammatory Efficacy in Mice Bearing a Nonfunctional MC1R (Recessive Yellow e/e Mouse)
Mol. Pharmacol.,
December 1, 2006;
70(6):
1850 - 1855.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Getting, C. W. Lam, A. S. Chen, P. Grieco, and M. Perretti
Melanocortin 3 receptors control crystal-induced inflammation
FASEB J,
November 1, 2006;
20(13):
2234 - 2241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Xie, A. Plagge, O. Gavrilova, S. Pack, W. Jou, E. W. Lai, M. Frontera, G. Kelsey, and L. S. Weinstein
The Alternative Stimulatory G Protein {alpha}-Subunit XL{alpha}s Is a Critical Regulator of Energy and Glucose Metabolism and Sympathetic Nerve Activity in Adult Mice
J. Biol. Chem.,
July 14, 2006;
281(28):
18989 - 18999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Tallam, A. A. da Silva, and J. E. Hall
Melanocortin-4 Receptor Mediates Chronic Cardiovascular and Metabolic Actions of Leptin
Hypertension,
July 1, 2006;
48(1):
58 - 64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Lloyd, S. Bohan, and N. Gekakis
Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice
Hum. Mol. Genet.,
June 1, 2006;
15(11):
1884 - 1893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Garcia, I. Wernstedt, A. Berndtsson, M. Enge, M. Bell, O. Hultgren, M. Horn, B. Ahren, S. Enerback, C. Ohlsson, et al.
Mature-onset obesity in interleukin-1 receptor I knockout mice.
Diabetes,
May 1, 2006;
55(5):
1205 - 1213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. O. Kasper, C. S. Carter, C. M. Ferrario, D. Ganten, L. F. Ferder, W. E. Sonntag, P. E. Gallagher, and D. I. Diz
Growth, metabolism, and blood pressure disturbances during aging in transgenic rats with altered brain renin-angiotensin systems
Physiol Genomics,
November 17, 2005;
23(3):
311 - 317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Koegler, P. J. Enriori, S. K. Billes, D. L. Takahashi, M. S. Martin, R. L. Clark, A. E. Evans, K. L. Grove, J. L. Cameron, and M. A. Cowley
Peptide YY(3-36) Inhibits Morning, but Not Evening, Food Intake and Decreases Body Weight in Rhesus Macaques
Diabetes,
November 1, 2005;
54(11):
3198 - 3204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Stanley, K. Wynne, B. McGowan, and S. Bloom
Hormonal Regulation of Food Intake
Physiol Rev,
October 1, 2005;
85(4):
1131 - 1158.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Sutton, B. Duos, L. M. Patterson, and H.-R. Berthoud
Melanocortinergic Modulation of Cholecystokinin-Induced Suppression of Feeding through Extracellular Signal-Regulated Kinase Signaling in Rat Solitary Nucleus
Endocrinology,
September 1, 2005;
146(9):
3739 - 3747.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Maejima, M. Aoyama, A. Abe, and S. Sugita
Induced expression of c-fos in the diencephalon and pituitary gland of goats following transportation
J Anim Sci,
August 1, 2005;
83(8):
1845 - 1853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Bischof and R. Wevrick
Genome-wide analysis of gene transcription in the hypothalamus
|
TOP
ABSTRACT
I. Introduction
