Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adipose tissue-derived hormone leptin regulates body weight homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus. We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms. The antiserum recognized the short and long isoforms of LR in transfected hematopoietic BaF3 cells. To examine the chemical nature of target cells for leptin, direct double-labeling immunofluorescence histochemistry was applied. The results show extensive distribution of LR-like immunoreactivity (LR-LI) in the brain with positively stained cells present, e.g., in the choroid plexus, cerebral cortex, hippocampus, thalamus, and hypothalamus. In the hypothalamus, strongly LR-IR neurons were present in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), periventricular nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR neurons were also demonstrated in the lateral and medial preoptic nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei, and tuberomammillary nucleus. Confocal laser scanning microscopy showed LR-LI in the periphery of individual cells. In magnocellular neurons of the SON and PVN, LR-LI was demonstrated in vasopressin- and oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI was demonstrated in many corticotropin-releasing hormone-containing neurons. LR-IR neurons were mainly seen in the ventromedial aspect of the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR proopiomelanocortin-containing neurons and in a few galanin-, neurotensin-, and growth hormone-releasing hormone-containing neurons. In the dorsomedial arcuate nucleus, few tyrosine hydroxylase (dopamine)-containing neurons were seen to have LR-LI. Melanin-concentrating hormone-containing neurons in the lateral hypothalamus had LR-LI. Based on the immunohistochemical results, possible interactions of leptin with brain mechanisms are discussed.
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PMID:Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. 941 31

Leptin, a product of the obese (ob) gene, is secreted by adipocytes and appears to act as a hormone to regulate food intake, metabolism and body weight. Subcutaneous administration of leptin causes reductions in food intake and body and fat-depot weights in both lean and genetically obese (ob/ob) mice, and leptin infusion into the lateral cerebral ventricles decreases feeding with short latency, suggesting a central site of action. A gene defect in the Zucker obese rat causes an amino acid substitution in the leptin receptor and reduced leptin binding at the cell surface. An antiserum to a portion of the mouse leptin receptor (AA 877-894) located within the intracellular domain was used to label Zucker lean (Fa/?) and obese (fa/fa) rat brain sections. At optimal dilution (1:8000), only cells in the basal forebrain, preoptic area, hypothalamus and brainstem were moderately or intensely labeled. The most intensely-labeled nuclei, the anterior commissural, magnocellular paraventricular, supraoptic, circularis in the anterior hypothalamus and fornical in the lateral hypothalamus contain large neurons that synthesize and secrete vasopressin or oxytocin and their respective neurophysins. Diminished leptin transport into the central nervous system or defective signal transduction in Zucker obese rats may sufficiently compromise leptin regulation of the HPA axis, NPY-immunoreactive neurons or other hypothalamic elements to cause obesity.
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PMID:Localization of leptin receptor immunoreactivity in the lean and obese Zucker rat brain. 952 52

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle-stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and appears to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long-sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH, and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha1 receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor-alpha (TNF-alpha). In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants by stimulating the release of NO. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
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PMID:Hypothalamic control of FSH and LH by FSH-RF, LHRH, cytokines, leptin and nitric oxide. 973 Jun 86

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and seems to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin, and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA, and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha, (alpha 1) receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor (TNF) alpha. In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP, which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
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PMID:Hypothalamic control of gonadotropin secretion by LHRH, FSHRF, NO, cytokines, and leptin. 978 37

The present studies were designed to examine the regulation of leptin release in primary cultures of adipocytes from fed hypothyroid rats incubated with hormones for 24 hours. Leptin release was increased in the presence of dexamethasone, while the decrease in leptin mRNA content over a 24-hour incubation was reduced by dexamethasone. Dexamethasone did not affect the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA or 18S RNA content of adipocytes. Insulin increased leptin release by adipocytes in both the absence and presence of dexamethasone. Although insulin also prevented the loss of leptin mRNA, this effect was less than that observed for GAPDH mRNA or 18S RNA content. In isolated adipocytes, the loss of almost half the 18S RNA content over a 24-hour incubation was prevented in the presence of insulin but not oxytocin or epidermal growth factor (EGF). The specific beta3 catecholamine agonist CI 316,243 inhibited the effects of dexamethasone on leptin release and leptin mRNA accumulation, as did EGF, without affecting 18S RNA content. Oxytocin inhibited the increase in leptin release due to dexamethasone without affecting leptin mRNA levels. These data indicate that although dexamethasone and insulin are positive regulators of leptin release, only dexamethasone specifically prevented the loss of leptin mRNA in cultured rat adipocytes. In contrast, insulin, but not dexamethasone, prevented the marked loss in 18S RNA observed over a 24-hour incubation of rat adipocytes.
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PMID:Hormonal regulation of 18S RNA, leptin mRNA, and leptin release in adipocytes from hypothyroid rats. 986 73

The product of the ob gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.
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PMID:Centrally administered murine leptin stimulates plasma arginine-vasopressin secretion and increases the level of mRNA expression in the supraoptic nucleus of conscious rats. 1051 84

Distinct brain peptidergic circuits govern peripheral energy homeostasis and related behavior. Here we report that mitochondrial uncoupling protein 2 (UCP2) is expressed discretely in neurons involved in homeostatic regulation. UCP2 protein was associated with the mitochondria of neurons, predominantly in axons and axon terminals. UCP2-producing neurons were found to be the targets of peripheral hormones, including leptin and gonadal steroids, and the presence of UCP2 protein in axonal processes predicted increased local brain mitochondrial uncoupling activity and heat production. In the hypothalamus, perikarya producing corticotropin-releasing factor, vasopressin, oxytocin, and neuropeptide Y also expressed UCP2. Furthermore, axon terminals containing UCP2 innervated diverse hypothalamic neuronal populations. These cells included those producing orexin, melanin-concentrating hormone, and luteinizing hormone-releasing hormone. When c-fos-expressing cells were analyzed in the basal brain after either fasting or cold exposure, it was found that all activated neurons received a robust UCP2 input on their perikarya and proximal dendrites. Thus, our data suggest the novel concept that heat produced by axonal UCP2 modulates neurotransmission in homeostatic centers, thereby coordinating the activity of those brain circuits that regulate daily energy balance and related autonomic and endocrine processes.
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PMID:Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers. 1057 39

Diabetes mellitus is not a diagnostic criterion for Prader-Willi syndrome (PWS), but it is often found in PWS patients. The etiology for diabetes mellitus in PWS may be related to the morbid obesity and consequent insulin resistance, because a decrease of oxytocin neurons and leptin resistance in PWS may cause hyperphagia, inducing obesity. However, treatment with growth hormone (GH) is beneficial for the majority of GH-deficient PWS children, because relative decreased fat mass and increased fat-free mass could prevent obesity and concomitant insulin resistance. Hypogonadism is thought to be due to hypogonadotrophic hypogonadism in a majority of PWS patients. Hypergonadotrophic hypogonadism secondary to cryptorchidism and its treatment is shown in other cases. Low luteinizing hormone and high follicle-stimulating hormone levels in PWS cases in young men with idiopathic oligospermia or in the early stages of puberty is less frequently reported.
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PMID:Prader-Willi syndrome, diabetes mellitus and hypogonadism. 1066 37

To establish whether the regulatory mechanism of leptin secretion is sensitive to oxytocin (OT), seven healthy nonobese men were tested with dexamethasone (dex; 4 mg, iv, at 0730 h) in feeding (2000 Cal given at 3 meals over 7 h) conditions either in the absence (iv normal saline infusion) or in the presence of a constant iv infusion of OT (1, 2, or 4 mIU/min from 0730 h for 10 h). In six additional subjects under similar experimental conditions, normal saline or OT (1, 2, or 4 mIU/min from 0730 h for 10 h) were infused iv without the previous treatment with dexamethasone. Serum leptin concentrations were measured in samples taken at 60-min intervals during infusion. Leptin levels remained constant during the infusion of normal saline or OT (1, 2, or 4 mIU/min) alone. In contrast, serum leptin concentrations rose significantly from the baseline after dex administration. The leptin response to dex was not modified by the concomitant infusion of 1 mIU/min OT, whereas it was completely abolished by the administration of 2 or 4 mIU/min OT. These findings led us to evaluate the secretory pattern of leptin in 12 obese patients in similar experimental conditions. In all patients basal leptin levels were significantly higher than those in normal weight subjects. In 6 obese subjects, the infusion of OT alone (1, 2, or 4 mIU/min) was unable to change serum leptin levels. In the remaining 6 obese subjects, dex administration significantly increased serum leptin levels; however, the leptin response to dex was not modified by the concomitant infusion of 1, 2, or 4 mIU/min OT. These data show inhibition by elevated circulating OT levels of glucocorticoid-induced, but not basal, leptin secretion in normal weight subjects, suggesting a possible role for OT in the regulatory control of leptin. Furthermore, the results obtained in obese subjects indicate that this regulation is disrupted in obesity.
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PMID:Effect of systemic oxytocin administration on dexamethasone-induced leptin secretion in normal and obese men. 1106 23

During lactation, hypothalamic levels of neuropeptide Y (NPY) and agouti related protein (AGRP) mRNA are increased, while pro-opiomelanocortin (POMC) mRNA is decreased. Serum leptin levels are also decreased during lactation. These changes may underlie the large increases of both food and water intake that occur in concert with milk production. However, additional hypothalamic substances, such as the novel peptide, orexin, may be involved. In addition, in the presence of chronically suppressed levels of serum leptin, there may be a change in leptin receptor expression in the hypothalamus. The objectives of the present study were to determine if orexin and leptin receptor mRNA levels were changed during lactation. Rats were studied on dioestrus of the oestrous cycle or on day 10 postpartum (the lactating animals were suckling eight pups). Orexin mRNA levels in the lateral hypothalamus did not differ between dioestrus and lactation. There was a significant increase in leptin receptor mRNA levels in the supraoptic nucleus during lactation compared to dioestrus. Furthermore, leptin receptor protein, as determined by immunocytochemistry, was colocalized in virtually all vasopressin and oxytocin cells in the supraoptic nucleus. Lactating animals exhibited a decrease in leptin receptor mRNA in the ventromedial hypothalamic nucleus whereas no change was apparent in other hypothalamic areas compared to the dioestrus animals. These results demonstrate that changes in orexin do not appear to contribute to the increase in food intake during lactation. It is likely that the increases in NPY and ARGP, coupled with the decrease in POMC, are primarily responsible for sustaining the chronic hyperphagia of lactation. The changes observed in leptin receptor expression in the hypothalamus, along with the suppression of serum leptin levels, also suggest that the leptin signalling system may play a significant role in the regulation of food and water intake during lactation.
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PMID:Differential regulation of leptin receptor but not orexin in the hypothalamus of the lactating rat. 1106 23


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