Disease relevance of Hypothalamus

• Agouti protein, a paracrine signaling molecule normally limited to skin, is ectopically expressed in lethal yellow (A(y)) mice, and causes obesity by mimicking agouti-related protein (Agrp), found primarily in the hypothalamus [1].
• The hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuropeptides, such as neuropeptide Y (ref. 1), galanin, CRH (ref. 3) and GLP-1 (ref. 4), have been implicated in the mediation of these effects [2].
• Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia [3].
• Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats [4].
• A biphasic effect of thyroid hormone on pituitary GH levels appears to derive from the difference in primary target tissues of hyper- and hypothyroidism, the hypothalamus and the pituitary, respectively [5].

Psychiatry related information on Hypothalamus

• These results implicate EGF receptor signaling in the daily control of locomotor activity, and identify a neural circuit in the hypothalamus that likely mediates the regulation of behavior both by the SCN and the retina [6].
• Here we highlight the role of the hypothalamus in sleep physiology and discuss neurotransmitter systems, such as adenosine, dopamine, GABA, histamine and hypocretin, that may have therapeutic applications for sleep disorders [7].
• These data reveal an intricate and asymmetric interplay between NPY and POMC neurons in the hypothalamus and have important implications for the delineation of the neural circuits that regulate feeding behavior [8].
• It is suggested that the early-morning growth-hormone release associated with slow-wave sleep is due to inhibition of somatostatin secretion from the hypothalamus [9].
• These results suggest increased 5-HT receptor sensitivity may be present, possibly in the hypothalamus or pituitary, in some patients with affective disorders [10].

High impact information on Hypothalamus

• It is proposed that, toward the end of the luteal phase, loss of progesterone action occurs both centrally in the hypothalamus and in the uterus due to the catalytic reduction (downregulation) of progesterone receptors by progesterone [11].
• The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown [12].
• Nhlh2 is expressed in the ventral-medial and lateral hypothalamus, Rathke's pouch and in the anterior lobe of the adult pituitary [13].
• The leptin receptor (Ob-R) is found in many tissues in several alternatively spliced forms raising the possibility that leptin exerts effects on many tissues including the hypothalamus [14].
• Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function [15].

Chemical compound and disease context of Hypothalamus

• Thyrotoxicosis, induced by administration of thyroxine (T4) in rats, inhibited both pituitary GH levels and immunoreactive GRF secretion from incubated hypothalamus [5].
• INTERPRETATION: Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache [16].
• E- and P-binding neurons important for lordosis behavior have been located within the ventromedial hypothalamus (VMH), and several hormone-responsive genes have been observed there as well [17].
• We examined the possibility that alterations in the timing of cyclic luteinizing hormone (LH) release during the middle age transition to infertility reflect differences in the circadian pattern of neural function in pacemaker areas of the hypothalamus, particularly the suprachiasmatic nucleus [18].
• cDNA clones corresponding to the polypeptide that has been shown to be an endogenous diazepam binding inhibitor and may act as a physiological ligand for the benzodiazepine/beta-carboline receptor have been isolated from bacteriophage lambda recombinant libraries from rat hypothalamus, total brain, and liver [19].

Biological context of Hypothalamus

• Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance [20].
• The regional distribution of the specific binding sites for 3H-substance P parallels that of substance P immunoreactivity, being high in the hypothalamus and low in the cerebellum and cerebral cortex [21].
• It has been proposed that leptin acts in the hypothalamus, the main control centre for satiety and energy expenditure [22].
• This suggests that the weight-reducing effects of leptin may be mediated by signal transduction through a leptin receptor in the hypothalamus [23].
• The neuropeptide oxytocin, synthesized by magnocellular neurones in the hypothalamus, is well known for its peripheral action during lactation and parturition after its release into the bloodstream from axons in the neurohypophysis [24].

Anatomical context of Hypothalamus

• The finding of increasing fetal serum concentrations of thyroid-stimulating hormone in the presence of increasing thyroid hormone concentrations suggests that the sensitivity of the fetal pituitary gland to negative feedback is limited or is counterbalanced by increasing stimulation by thyrotropin-releasing hormone from the hypothalamus [25].
• OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus [26].
• We further report that about 60% of the CCK in posterior lobe originates in cell bodies in the paraventricular nucleus of the hypothalamus [27].
• On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus [28].
• Recent experiments performed in vivo indicate that relaxin might act not only in the uterus, but also in the hypothalamus and possibly in the neurohypophysis [29].

Associations of Hypothalamus with chemical compounds

• Here we describe the mutant foggy, identified in a genetic screen for mutations that affect neuronal development in zebrafish, that displayed a reduction of dopamine-containing neurons and a corresponding surplus of serotonin-containing neurons in the hypothalamus [30].
• Met-enkephalin inhibits in vitro dopamine-induced LHRH release from mediobasal hypothalamus of male rats [31].
• Oestradiol, sexual receptivity and cytosol progestin receptors in rat hypothalamus [32].
• The suprachiasmatic nuclei (SCN) of the hypothalamus, a source of vasopressin production, inhibit sexual receptivity in oestradiol-17 beta-treated ovariectomized rats during the light phase of the daily lighting cycle, leading to speculation that vasopressin might inhibit sexual behaviour [33].
• A number of neurotransmitters in the hypothalamus, including gamma-aminobutyric acid (GABA), also have key roles in feeding [34].

Gene context of Hypothalamus

• Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus [20].
• Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus [35].
• The predicted protein encoded by Mgca is a 1,428-amino-acid, single-transmembrane-domain protein that is expressed in many tissues, including pigment cells and the hypothalamus [36].
• CB1 cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus, and marijuana and anandamide stimulate food intake [20].
• NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting [37].

Analytical, diagnostic and therapeutic context of Hypothalamus

• Glutamate has been found to play an unexpectedly important role in neuroendocrine regulation in the hypothalamus, as revealed in converging experiments with ultrastructural immunocytochemistry, optical physiology with a calcium-sensitive dye, and intracellular electrical recording [38].
• Microinjections of the excitatory neurotoxin kainic acid into the lateral hypothalamus of rats produced a period aphagia and adipsia [39].
• Abdominal vagotomy or gastric vagotomy abolished or reduced the satiety effect of cholecystokinin, but lesions of the ventromedial hypothalamus did not [40].
• To investigate Sim1 function in the hypothalamus, we produced mice carrying a null allele of Sim1 by gene targeting [41].
• By using double label in situ hybridization, AT1A receptor expression was localized in corticotropin releasing hormone but not in vasopressin containing neurons in the hypothalamus [42].

References