Hypothalamus

About: Hypothalamus is a research topic. Over the lifetime, 22301 publications have been published within this topic receiving 1085925 citations.

Interleukins-1 and -6 stimulate the release of corticotropin-releasing hormone-41 from rat hypothalamus in vitro via the eicosanoid cyclooxygenase pathway.

Abstract: It has previously been shown that interleukin-1 (IL-1) directly stimulates the release of CRH-41 from rat hypothalamus in vitro, suggesting that cytokines may mediate the effects of changes in immune state on the hypothalamo-pituitary adrenal axis (HPA). However, it is likely that several cytokines can cause changes in neuroendocrine function, and we have now investigated a series of others for central activity on the HPA: IL-2, IL-6, IL-8, tumor necrosis factor (cachectin), interferon-alpha 2, and interferon-gamma. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubation, and estimation of CRH-41 concentrations in the medium by a specific RIA; the acute effects of cytokines on ACTH release from rat dispersed pituitary cells were also measured. IL-6 increased hypothalamic CRH-41 secretion in the range 10-100 U/ml, but had no effect on isolated median eminences incubated in vitro under the same conditions. IL-6 (1-1000 U/ml) also had no effect on the secretion of ACTH from freshly dispersed rat anterior pituitary cells when administered in 10-min pulses. The effects of both IL-1 and IL-6 were antagonized by blockade of the eicosanoid cyclooxygenase pathway, but not by lipooxygenase blockade. Neither IL-2 (1-10000 U/ml), IL-8 (0.1-10 nM), tumor necrosis factor (10-1000 U/ml), interferon-alpha 2 (10-1000 U/ml) nor interferon-gamma (10-1000 U/ml) had any effect on hypothalamic CRH-41 release or pituitary ACTH release. It is therefore concluded that IL-6, like IL-1, can exert a potent enhancing effect on the HPA by acutely stimulating the secretion of CRH-41 from the hypothalamus at a site above the level of the median eminence, at concentrations known to occur in human plasma and cerebrospinal fluid. These effects are probably mediated by cyclooxygenase products. Acute stimulatory effects of the other cytokines investigated on the HPA are unlikely to be exerted through changes in either CRH-41 or ACTH directly.

Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro

Abstract: THE peptides somatostatin and neurotensin were first described in extracts of mammalian hypothalamus1–3. The recent development of sensitive radioimmunassay techniques and the application of immunohistochemical studies have shown that these peptides are concentrated in nerve terminals in various regions of the central nervous system (CNS)4–12. Somatostatin-containing nerve terminals are particularly abundant in the median eminence of the hypothalamus, from which somatostatin seems to be released as a hypophysiotropic hormone controlling the secretion of growth hormone from the anterior pituitary7. Somatostatin is also present in a variety of glandular tissues, in the gastrointestinal tract8,9, and in nerve terminals in many areas of the CNS outside the hypothalamus4–6. Neurotensin is similarly present in high concentration in the hypothalamus, and is also found in other areas of the CNS, in the gastrointestinal tract and in pituitary gland10–12. Within the CNS, the unique localisation of these peptides in specific systems of neurones suggests that they may be released as neurotransmitters or neuromodulators, as has been proposed for other neuropeptides such as substance P (ref. 13) and the enkephalins14. So far, however, it has not been shown that somatostatin or neurotensin can be released from CNS neurones, although a calcium-dependent release of somatostatin was recently reported from neurohypophyseal tissue in vitro15. We describe here the release of both somatostatin and neurotensin from rat brain tissue in vitro by a calcium-dependent mechanism, thus lending further support to the hypothesis that they may normally be released from nerve terminals within the CNS.

Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively.

Abstract: POMC-derived melanocortins inhibit food intake. In the adult rodent brain, POMC-expressing neurons are located in the arcuate nucleus (ARC) and the nucleus tractus solitarius (NTS), but it remains unclear how POMC neurons in these two brain nuclei regulate feeding behavior and metabolism differentially. Using pharmacogenetic methods to activate or deplete neuron groups in separate brain areas, in the present study, we show that POMC neurons in the ARC and NTS suppress feeding behavior at different time scales. Neurons were activated using the DREADD (designer receptors exclusively activated by designer drugs) method. The evolved human M3-muscarinic receptor was expressed in a selective population of POMC neurons by stereotaxic infusion of Cre-recombinase–dependent, adeno-associated virus vectors into the ARC or NTS of POMC-Cre mice. After injection of the human M3-muscarinic receptor ligand clozapine-N-oxide (1 mg/kg, i.p.), acute activation of NTS POMC neurons produced an immediate inhibition of feeding behavior. In contrast, chronic stimulation was required for ARC POMC neurons to suppress food intake. Using adeno-associated virus delivery of the diphtheria toxin receptor gene, we found that diphtheria toxin–induced ablation of POMC neurons in the ARC but not the NTS, increased food intake, reduced energy expenditure, and ultimately resulted in obesity and metabolic and endocrine disorders. Our results reveal different behavioral functions of POMC neurons in the ARC and NTS, suggesting that POMC neurons regulate feeding and energy homeostasis by integrating long-term adiposity signals from the hypothalamus and short-term satiety signals from the brainstem.

Localization and Characterization of Insulin Receptors in Rat Brain and Pituitary Gland Using in Vitro Autoradiography and Computerized Densitometry

Abstract: In order to identify likely sites of action in insulin in rat brain we have used the technique of in vitro autoradiography and computerized densitometry to map, characterize, and quantify its receptors in coronal and sagittal sections A discrete and characteristic distribution of insulin receptor binding was demonstrated, with specific binding representing 92% of total binding Displacement and specificity competition curves in olfactory bulb are typical for authentic insulin receptors, and computer analysis indicates a single class of binding site with a dissociation constant (Kd) 048 nM for choroid plexus and 044 nM for olfactory bulb external plexiform layer Insulin receptor density is maximum in the choroid plexus, and high in the external plexiform layer of olfactory bulb Structures of the limbic system and hypothalamus reveal moderate to high insulin receptor density, particularly the lateral septum, amygdala, subiculum, hippocampal CA1 region, mammillary body, and arcuate nucleus Moderate ins