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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of monosodium-L-glutamate (MSG) during the neonatal period is known to result in central nervous system lesions in the arcuate nucleus of the hypothalamus and the retina. Rodents so treated exhibit behavioral deficts and endocrinopathies including obesity, hypogonadism, hypothyroidism, pituitary atrophy, tail automutilation and diminished locomotor activity. Assessment of endocrine status revealed normal serum levels of glucagon, thyroid-stimulating hormone and luteinizing hormone, and diminished levels of thyroid hormones and growth hormone in MSG-treated rats. Prolactin levels were elevated in the glutamate-treated male rats. Within the brain hypothalamic levels of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and somatostatin were unchanged. Measurement of neurotransmitters and neurotransmitter-related enzymes in individual hypothalamic nuclei derived from MSG-treated rats revealed normal levels of norepinephrine, serotonin and glutamic acid decarboxylase, but reduced levels of choline acetyltransferase and dopamine in the arcuate nucleus and median eminence. Histochemical methods for visualization of dopamine and acetylcholinesterase in the mediobasal hypothalamus confirmed these findings. The MSG-treated animals exhibited a normal diurnal rhythm of pineal serotonin N-acetyltransferase activity. These data indicate that the MSG-induced endocrine deficiency syndrome results at least partly from destruction of cholinergic and dopamingeric tuberoinfundibular systems in the hypothalamus.
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PMID:Models of neuroendocrine regulation: use of monosodium glutamate as an investigational tool. 3 35

Intravenous insulin tolerance tests and thyrotropin-releasing hormone (T.R.H.) stimulation tests were performed in nine massively obese women and six lean female controls and the prolactin, growth hormone, and cortisol responses were measured. A combined pituitary function test (insulin, T.R.H., and gonadotropin-releasing hormone) was performed in eleven other massively obese women. In the obese women to whom insulin was given separately there was no prolactin release, and growth hormone and cortisol responses were impaired. T.R.H. stimulation produced a prolactin response which was subnormal. These changes were not apparent in the obese women in whom a combined pituitary function test was performed. The results suggest an alteration of hypothalamic function in massive obesity.
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PMID:Impaired hypothalamic control of prolactin secretion in massive obesity. 8 90

During pregnancy estrogen-medicated augmented prolactin secretion is presumably responsible for a 10-20 fold increase in circulating plasma prolactin; significant differences in basal levels between nursing and nonnursing women persist into the puerperium, reflecting the influence of sucking on maternal plasma prolactin. The release of prolactin is induced via a neurogenic pathway from nipple to hypothalamus and it is proportionate to the length of nursing and to the intensity of the stimulus. There is evidence supporting catecholamine/serotonin control of prolactin release, and the influence of changes in hypothalamic dopamine turnover. The composition of human milk is dependent on various factors; overall, fat composition is 2-5% and protein 9% at 3 weeks and 5% thereafter; milk delivers 20-25 calories per ounce; total fluid and nutritional requirements of the newborn can be met by breastfeeding up to 6 months postpartum. Maternal malnutrition negatively affects lactation; gestational, rather than progestational, food intake influences lactation. Immunity in the newborn is provided also by breast milk through immunoglobulins, thus enhancing the child's protection against internal pathogens. The incidence of gastrointestinal disorders is 1.5/1000 in breastfed infants, and 84.7/1000 in bottle fed infants; the incidence of respiratory infection is .4/1000 and 48/1000, respectively. Prolactin may exert an inhibitory influence on ovarian steroidogenesis, and gonadotropin secretion is disrupted by nipple stimuation; this may account for the low percentage of ovulation among nursing mothers. Lactational amenorrhea has been proven to have great demographic impact; dramatic variations in fertility on the basis of variations in lactational amenorrhea have been described in rural areas of Latin America, Asia, and Africa. Reduction of lactational amenorrhea results not only from changes in sociocultural patterns, but from improved maternal nutrition, often through nutrition programs. When nursing has to be interrupted because of complications full lactation may be restored by oral administration of thyrotropin-releasing hormone. Breastfeeding is possible in 99% of women; the denial of lactation may cause the retention of unwanted weight, which can be compounded by the use of oral contraceptives. Moreover, infantile obesity may stem from the lack of a satiety signal in bottle fed newborns.
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PMID:Mechanisms of puerperal lactation. 83 86

To test whether short-term fasting has a different effect on hormone release from lactotrophs and thyrotrophs in normal-weight men compared with obese men, 10 mg metoclopramide (MET) was administered orally to seven normal and six obese men before and after a 56-hour fast. In the normal subjects, MET raised the serum prolactin (PRL) level before fasting from 5.1 +/- 1.3 to 58.6 +/- 9.5 micrograms/L in 60 minutes (P less than .02), but left the thyrotropin (TSH) level unaffected. An almost identical hormone response was seen after fasting. Obese men responded differently. Their lactotrophs were initially refractory to MET stimulation (PRL increase from 9.5 +/- 5.1 to 17.5 +/- 5.7 micrograms/L, NS), but became sensitive to such stimulation after fasting (PRL increase from 8.2 +/- 4.5 to 46.3 +/- 6.7 micrograms/L, P less than .01). The thyrotrophs were unaffected by MET before, as well as after, the fast. Although decreased PRL synthesis, reduced cell membrane permeability, and inadequate MET stimulation are plausible mechanisms by which the reduced PRL responsiveness to MET could be explained in the obese patients, neither is likely in view of the fact that the lactotrophs responded promptly to thyrotropin-releasing hormone (TRH), administered intravenously (IV) 60 minutes after MET, in the fed obese patients (PRL increase after TRH from 17.5 +/- 5.7 to a maximum of 48.0 +/- 8.7 micrograms/L, P less than .05). Furthermore, a 50% reduction of the MET dose (5 mg) resulted in a significant PRL response in non-obese healthy men (PRL increase from 3.1 +/- 1.1 to 40.3 +/- 0.9 micrograms/L, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased dopaminergic control of prolactin secretion in male obesity: normalization by fasting. 189 23

The mechanisms whereby growth hormone (GH) secretion is decreased in human obesity remain obscure. We studied the response of plasma GH and prolactin (PRL) to an I.V. dose of 0.5 mcg/kg of growth hormone releasing factor (GRF) in three groups of children: lean (N = 12), obese (N = 15) and GRF-deficient, i.e. children with complete GH deficiency on the basis of conventional provocative testing and evidence of hypothalamic dysfunction on the basis of thyrotropin-releasing hormone testing (N = 7). Mean (+/- SEM) peak plasma GH after GRF was blunted to the same extent in obese and in GRF deficient children (11.1 +/- 2.2 and 8.3 +/- 2.8 ng/ml) as compared to lean control children (34.7 +/- 4.7 ng/ml). The pattern of PRL response to GRF was however different in GRF deficient children, whose high basal PRL levels increased further after GRF injection, and in obese and lean children, who had n alpha acute change in PRL levels after GRF. Baseline plasma somatomedin C concentrations were low for age in GRF deficient children and tended to be high for age in obese children. On the basis of these discrepant patterns of response of PRL to GRF and plasma somatomedin C concentrations, we conclude that GRF deficiency does not account for the decreased GH secretion observed in obese children.
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PMID:Evidence against growth hormone-releasing factor deficiency in children with idiopathic obesity. 309 43

Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature.
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PMID:The Prader-Willi syndrome: a study of 40 patients and a review of the literature. 633 43

We studied insulin-like growth factors (IGF) I and II, prolactin, and the insulin response to arginine in 19 children with craniopharyngioma and documented growth hormone deficiency. Patients were divided into three groups according to their growth rate during the first postoperative year. Seven patients with excessive growth (Group A) had hyperinsulinism, normal IGF values, elevated basal prolactin levels, and a delayed thyrotropin response to thyrotropin-releasing hormone, which was compatible with hypothalamic lesions. In the six patients with normal growth (Group B), the insulin level was low; all other hormone values were similar to those of Group A. In the six patients with decreased growth (Group C), levels of IGF I, insulin, prolactin, and thyrotropin were low, indicating the presence of severe pituitary damage and explaining the failure to grow. Patients in all groups had low or undetectable basal levels of growth hormone. We conclude that in Group B, normal IGF permitted normal growth, and prolactin hypersecretion may have been responsible for normal IGF I values. Excessive growth in Group A may have been caused by hyperinsulinism associated with hyperphagia and obesity of hypothalamic origin.
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PMID:Insulin-like growth factors I and II, prolactin, and insulin in 19 growth hormone-deficient children with excessive, normal, or decreased longitudinal growth after operation for craniopharyngioma. 635 37

The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/ autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years.
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PMID:The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. 1099 9

Food intake is a regulated system. Afferent signals provide information to the central nervous system, which is the centre for the control of satiety or food seeking. Such signals can begin even before food is ingested through visual, auditory and olfactory stimuli. One of the recent interesting findings is the demonstration that there are selective fatty acid taste receptors on the tongue of rodents. The suppression of food intake by essential fatty acids infused into the stomach and the suppression of electrical signals in taste buds reflect activation of a K rectifier channel (K 1.5). In animals that become fat eating a high-fat diet the suppression of this current by linoleic acid is less than that in animals that are resistant to obesity induced by dietary fat. Inhibition of fatty acid oxidation with either mercaptoacetate (which blocks acetyl-CoA dehydrogenase) or methylpalmoxirate will increase food intake. When animals have a choice of food, mercaptoacetate stimulates the intake of protein and carbohydrate, but not fat. Afferent gut signals also signal satiety. The first of these gut signals to be identified was cholecystokinin (CCK). When CCK acts on CCK-A receptors in the gastrointestinal tract, food intake is suppressed. These signals are transmitted by the vagus nerve to the nucleus tractus solitarius and thence to higher centres including the lateral parabrachial nucleus, amygdala, and other sites. Rats that lack the CCK-A receptor become obese, but transgenic mice lacking CCK-A receptors do not become obese. CCK inhibits food intake in human subjects. Enterostatin, the pentapeptide produced when pancreatic colipase is cleaved in the gut, has been shown to reduce food intake. This peptide differs in its action from CCK by selectively reducing fat intake. Enterostatin reduces hunger ratings in human subjects. Bombesin and its human analogue, gastrin inhibitory peptide (also gastrin-insulin peptide), reduce food intake in obese and lean subjects. Animals lacking bombesin-3 receptor become obese, suggesting that this peptide may also be important. Circulating glucose concentrations show a dip before the onset of most meals in human subjects and rodents. When the glucose dip is prevented, the next meal is delayed. The dip in glucose is preceded by a rise in insulin, and stimulating insulin release will decrease circulating glucose and lead to food intake. Pyruvate and lactate inhibit food intake differently in animals that become obese compared with lean animals. Leptin released from fat cells is an important peripheral signal from fat stores which modulates food intake. Leptin deficiency or leptin receptor defects produce massive obesity. This peptide signals a variety of central mechanisms by acting on receptors in the arcuate nucleus and hypothalamus. Pancreatic hormones including glucagon, amylin and pancreatic polypeptide reduce food intake. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte-stimulating hormone, growth hormone and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides that modulate feeding. beta-Casomorphin, a heptapeptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group, including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines and thyrotropin-releasing hormone, all decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors that relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
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PMID:Afferent signals regulating food intake. 1099 53

Leptin, an adipocyte-released hormone, modifies food intake and energy expenditure regulating hypothalamic-pituitary-thyroid axis function. We previously reported that thyrotropin-releasing hormone (TRH) precursor gene overexpression induces hypertension in the normal rat and that spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. In both models, intracerebroventricular antisense (AS) treatment against the TRH precursor produced a dose-dependent reduction of the increased diencephalic TRH content while normalizing high arterial blood pressure. In this article, we report that male Wistar rats that were made hypertensive by intracerebroventricular injection of a eucaryotic expression plasmid containing the pre-TRH cDNA showed decreased leptin plasma levels and that pre-TRH AS treatment reversed this phenomenon. In addition, male and female spontaneously hypertensive rats showed lower levels of circulating leptin than did sex-matched Wistar-Kyoto control rats. This difference also was abated by the pre-TRH AS treatment. Conversely, 20 microg ICV leptin induced a long-lasting pressor effect (18 +/- 5 mm Hg, n=6, P<0.01, >60 minutes) that was not observed in pre-TRH AS pretreated rats (2 +/- 3 mm Hg, n=6) but persisted in rats used as controls that were treated with inverted oligonucleotide (20 +/- 6 mm Hg, n=4, P<0.01). These data suggest that in rats with TRH-induced hypertension, leptin is decreased, inducing compensatory adiposity. We propose that because leptin produces central TRH synthesis and release, obesity may induce hypertension through TRH system activation and that the TRH-leptin interaction may thus contribute to the strong association between hypertension and obesity.
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PMID:Thyrotropin-releasing hormone decreases leptin and mediates the leptin-induced pressor effect. 1188 96


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