Hypothalamus

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

Evidence for Estrogen-Receptive GABAergic Neurons in the Preoptic/Anterior Hypothalamic Area of the Rat Brain

Abstract: Estrogen target neurons are numerous in the medial preoptic/anterior hypothalamic area (MPO/AH) of the female rat brain, and they are thought to play a crucial role in reproductive functions. This brain region is also known to contain high concentrations of the inhibitory transmitter gamma-aminobutyric acid (GABA) and of its synthesizing enzyme glutamate decarboxylase (GAD). Since it is known that GABA is involved in the regulation of gonadotropin release from the pituitary gland it has been proposed that estrogen feedback may be mediated by this transmitter. Here we show, by a combined method of estrogen autoradiography and GAD immunocytochemistry, that estrogen-receptive neurons of GABAergic nature exist in the MPO/AH.

Expression of Hypothalamic KiSS-1 System and Rescue of Defective Gonadotropic Responses by Kisspeptin in Streptozotocin-Induced Diabetic Male Rats

Abstract: Hypogonadotropism is a common feature of uncontrolled diabetes, for which the ultimate mechanism remains to be elucidated. Kisspeptins, ligands of G protein-coupled receptor 54 (GPR54) encoded by the KiSS-1 gene, have recently emerged as major gatekeepers of the gonadotropic axis. Alteration in the hypothalamic KiSS-1 system has been reported in adverse metabolic conditions linked to suppressed gonadotropins, such as undernutrition. However, its potential contribution to defective gonadotropin secretion in diabetes has not been evaluated. We report herein analyses of luteinizing hormone (LH) responses to kisspeptin and hypothalamic expression of the KiSS-1 gene in streptozotocin (STZ)-induced diabetic male rats. In addition, functional studies involving kisspeptin replacement or continuous administration of leptin and insulin to diabetic male rats are presented. Kisspeptin administration evoked robust LH and testosterone bursts and enhanced postgonadectomy LH concentrations, despite prevailing attenuation of gonadotropic axis in diabetic animals. In addition, hypothalamic KiSS-1 mRNA levels were unambiguously decreased in diabetic male rats, and the postorchidectomy rise in KiSS-1 mRNA was severely blunted. Repeated administration of kisspeptin to diabetic rats evoked persistent LH and testosterone responses and partially rescued prostate and testis weights. In addition, central infusion of leptin, but not insulin, was sufficient to normalize hypothalamic KiSS-1 mRNA levels, as well as LH and testosterone concentrations. In summary, we provide evidence for altered expression of the hypothalamic KiSS-1 system in a model of uncontrolled diabetes. This observation, together with the ability of exogenous kisspeptin to rescue defective LH responses in diabetic rats, unravel the physiopathological implication, and potential therapeutic intervention, of the KiSS-1 system in altered gonadotropin secretion of type 1 diabetes.

Serotonin and Appetite

Abstract: Feeding or food withdrawal can affect the supply of tryptophan to the brain and hence (in some circumstances) 5-HT synthesis therein. Also fenfluramine which releases 5-HT to postsynaptic receptors suppresses appetite, and there are reports that tryptophan can have a similar effect. Furthermore, feeding is reported to release hypothalamic 5-HT. Therefore 5-HT could have a role in the normal termination of feeding and perhaps also in disorders of appetite. The recognition of various 5-HT receptor subtypes has stimulated research in this area. We have now investigated the involvement of the subtypes in the pharmacological control of feeding. Thus, 5-HT1A agonists (8-OHDPAT, buspirone, gepirone, etc.) stimulate intake in freely feeding rats, probably by activating autoreceptors on the cell bodies of 5-HT neurons so that 5-HT release at terminals is decreased. The hyperphagia is not explicable by increased activity or gnawing and is strikingly manifest against carbohydrate in carbohydrate vs. protein choice experiments. Feeding in previously food-deprived rats is decreased by the 5-HT agonists RU 24969, 1-(3-chlorophenyl) piperazine (mCPP) and 1-(3-trifluoromethyl) phenyl) piperazine (TFMPP). Effects of antagonists on these properties suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors only, while mCPP and TFMPP induce hypophagia at 5-HT1C sites, though this effect also requires 5-HT1B receptors for its expression. Responsible sites occur in the paraventricular nucleus of the hypothalamus as infusing either RU 24969 or TFMPP therein causes hypophagia. On systemic injection, the hypophagic drugs are particularly active in female rats, an effect of conceivable relevance to human anorexic illness.