Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old Brazilian girl presented with severe growth retardation (-6.3 SDS), obesity, delayed pubertal development, facial dysmorphia, dry skin, and borderline low intelligence (IQ 89). Endocrinological evaluation showed primary hypothyroidism (no uptake of iodine-131 of the right thyroid lobe). Basal and stimulated gonadotropins were increased and ultrasonography revealed hypoplastic ovaries. The karyotype of peripheral lymphocytes was 46,X,i(Xq). The GH response in euthyroid condition after stimulation with GHRH and insulin was diminished. MRI of the pituitary region showed a suprasellar mass (12 x 15 mm) which was removed by transsphenoidal surgery because of extension to the optic chiasm. Histological examinations revealed regular pituitary tissue with hyperplasia of TSH- and FSH-producing cells. Thyroxine treatment was adjusted and GH was given. We conclude that the suprasellar mass was the consequence of long-lasting hypothalamic overstimulation with TRH and LHRH, due to gonadal and thyroid insufficiency.
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PMID:Pituitary hyperplasia in a girl with gonadal dysgenesis and primary hypothyroidism. 905 Sep 52

1. Studies of the regulation of neurosecretory cell gene expression suffer from the lack of suitable cell lines. Two approaches have been used to overcome this deficit: transfection of neuropeptide genes into heterologous cell lines and generation of transgenic animals. 2. Studies with heterologous cell lines have revealed the potential involvement of nuclear hormone receptors, POU proteins, and fos/jun/ATF family members in the regulation of the vasopressin and oxytocin genes. Although limited in their scope, these studies have contributed greatly to the dissection of basic properties of elements in the vasopressin and oxytocin gene promoters. 3. Transgenic mice, and more recently rats, have been used to elucidate genomic regions governing cell specificity and physiological regulation of neurosecretory gene expression. The genes encoding the neuropeptides vasopressin and oxytocin have been used in many transgenic studies, due to the well-defined expression patterns and physiology of the endogenous neuropeptides. Cell-specific and physiologically regulated expression of these transgenes has been achieved, demonstrating the action of putative repressor elements and regulation of the expression of one gene by sequences present in the other gene. 4. Appropriate expression and translation of transgenes have resulted in the production of several useful systems. Expression of oncogene sequences in gonadotropin-releasing hormone neurons has allowed the development of cell lines from the resulting tumors, overproduction of corticotropin-releasing factor has produced animal models of anxiety and obesity, and directed ectopic expression of growth hormone has generated a potentially useful rat model of dwarfism. These and other animal models of human disease will provide important avenues for the development of therapeutic strategies.
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PMID:Transgenic and transcriptional studies on neurosecretory cell gene expression. 953 88

Women with polycystic ovary syndrome come to the gynecologist with a variety of symptoms, including menstrual irregularities, hirsutism, acne, weight gain, obesity, and infertility. An accurate diagnosis requires both confirmation of signs and symptoms of polycystic ovary syndrome and exclusion of other disorders. Once the diagnosis of polycystic ovary syndrome has been established, the presence of concomitant conditions, such as hypertension, dyslipidemia, and diabetes, must be assessed. Because the cause of polycystic ovary syndrome is not clear, treatment options have focused on symptom management. Such treatment options include oral contraceptives, gonadotropin-releasing hormone analogs with "add-back" hormone regimens, antiandrogens, ovulation-inducing agents, electrolysis, nutritional and weight loss counseling, exercise, laparoscopic ovarian drilling, and glucocorticoids. Pathogenic considerations, risk factor assessments, and treatment objectives combine to determine the choice of therapies. It is not clear whether insulin resistance is clinically important or causal in polycystic ovary syndrome symptom complex in all affected women. Polycystic ovary syndrome may be the final common expression of a variety of metabolic or neuroendocrine perturbations. If insulin resistance is a universal feature, it would make sense to treat with an insulin-sensitizing agent in the expectation that symptoms would resolve or improve. If insulin resistance is not the main etiologic factor, however, then insulin-sensitizing agents would be useful as adjunctive agents only for women with clinically important insulin resistance (eg, patients with polycystic ovary syndrome in whom insulin resistance causes hyperglycemia). In such cases an insulin-sensitizing agent could be instituted along with a program of weight loss and exercise.
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PMID:The obstetrician-gynecologist's role in the practical management of polycystic ovary syndrome. 985 17

Leptin is a protein product from the obesity gene (ob gene). It has been shown that leptin significantly correlates with body mass index in humans. In contrast to the obesity of genetically obese (ob/ob) mice, human obesity is not generally caused by gene mutations. It is possible that human obesity results from central leptin resistance. Leptin can serve as a metabolic cue in the neuronal activation of gonadotropin releasing hormone (GnRH) at the end of the prepubertal period. The concentration of leptin is higher in pubertal girls than pubertal boys, and it is supposed that sexual dimorphism might be established in the prepubertal period or even in earlier developmental phases. This dimorphism could be explained by a suppressive action of androgens on leptin. Decreased leptin levels were found in undernourished women of reproductive age, mainly presenting with oligo- or amenorrhea. Leptin concentrations fluctuate according to the phase of the menstrual cycle. It is suggested that the complex relationship of leptin with other hormones, such as insulin, can have etiopathogenetic importance in some enigmatic reproductive disturbances such as the polycystic ovary syndrome. Recent findings of leptin in non-adipose tissue of the placenta could indicate its potential role in developmental physiology and human reproduction.
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PMID:Is there a role for leptin in human reproduction? 985 24

To assess the differential impact of the insulin secretory pattern and obesity on the endocrinometabolic features of the polycystic ovary syndrome (PCOS), we studied 110 PCOS women. Patients underwent a gonadotropin-releasing hormone (GnRH) test, an oral glucose tolerance test (OGTT), and basal evaluation of hormonal and biochemical parameters. Basal androgens and lipids, basal and stimulated gonadotropins, insulin, and glucose levels were measured. Patients were classified into four groups according to the body mass index (BMI) and insulin secretion: normoinsulinemic-lean ([NL] n = 24), normoinsulinemic obese ([NO] n = 24), hyperinsulinemic lean ([HL] n = 17), hyperinsulinemic obese ([HO] n = 45). HL patients showed a higher luteinizing hormone (LH) area under curve (AUC) after GnRH stimulus compared with NL patients (HL v NL, 4,285 +/- 348 v 3,377 +/- 314 IU/L x 120 min, P < .05), whereas we failed to find a statistically significant difference in a similar comparison among obese subjects (HO v NO, 3,606 +/- 302 v 3,129 +/- 602 IU/L x 120 min). A trend toward increased plasma testosterone and decreased sex hormone-binding globulin (SHBG) was found in relation to hyperinsulinemia and obesity, thus resulting in a higher free androgen index (FAI) in groups HL and NO versus NL (HL, 5.54 +/- 0.51; NO, 5.64 +/- 0.49; NL, 4.13 +/- 0.33; P < .05 and P < .01, respectively). The presence of both exaggerated insulin secretion and obesity resulted in a synergistic additive effect on the FAI in the HO group (6.81 +/- 0.34). Concerning the lipoprotein lipid profile, the NL group showed lower plasma triglyceride levels compared with the other three groups, whereas no significant differences were found for nonesterified fatty acid (NEFA) concentrations. Higher low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol (VLDL-C) and lower high-density lipoprotein cholesterol (HDL-C) levels were found in the obese groups compared with the lean counterparts, whereas the same parameters did not significantly differ in a comparison between normoinsulinemic and hyperinsulinemic groups. In conclusion, our data suggest an important role of hyperinsulinemia in the LH response to a GnRH stimulus and an independent and synergistic additive effect of obesity and hyperinsulinemia on the FAI in PCOS.
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PMID:Impact of insulin and body mass index on metabolic and endocrine variables in polycystic ovary syndrome. 1002 76

A special herbal tea has been used to treat clomiphene-resistant anovulatory disease and obesity effectively, especially in polycystic ovary syndrome (PCOS) cases with hyperinsulinemia. The effect of the herbal tea on obesity and anovulation was investigated in androgen-sterilized rats (ASR). The ASR model was established by subcutaneous injection of 1.25 mg testosterone propionate to Sprague-Dawley female rats at the age of 9 days. Rats were sacrificed around 112 days of age. ASR manifested with PCO, anovulation, high food intake, elevated body weight, and obesity. Immunocytochemistry demonstrated that estrogen receptors (ER) were predominantly distributed in the cytoplasm of neuropeptide Y (NPY)-containing neurons in the preoptic area (POA), and the coexpression was also found in the nuclei and fibers of NPY-synthesizing neurons in the arcuate nucleus (ARC). Compared with that in normal control rats, NPY expression was increased, the numbers of ER in hypothalamic ARC-median eminence (ME) decreased, gonadotropin-releasing hormone (GnRH) levels in ME was decreased, serum estrogen (E2) and leptin were elevated, and follicular stimulating hormone (FSH) and luteinizing hormone (LH) levels were reduced significantly in ASR. Significantly negative correlations between NPY and ER or GnRH, and between leptin and FSH or LH were observed. A positive correlation existed between serum leptin and body weight. These metabolic-endocrine changes in ASR were normalized after feeding the herbal tea. Both obesity and hypogonadotropin were expressed in ASR. The abnormal ovarian hormone milieu (elevated E2 levels) may have enhanced NPY expression and resulted in less GnRH and gonadotropin secretion. The herbal tea reduced body weight and induced ovulation in ASR.
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PMID:The effect of a special herbal tea on obesity and anovulation in androgen-sterilized rats. 1071 43

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

Several regulatory substances participate in the regulation of both food intake/energy metabolism and reproduction in mammals. Most of these neuropeptides originate and act in the central nervous system, mainly at specific hypothalamic areas. Leptin represents a signal integrating all these functions, but originating from the periphery (adipose tissue) and carrying information mainly to central structures. Observations in rodent models of leptin deficiency have suggested that leptin participates in the control of reproduction, in conjunction with that of food intake and energy expenditure. Indeed, leptin administration resulted in the restoration of normal body weight, food intake, and fertility in the ob mouse, lacking circulating leptin. Specific targets of leptin in the hypothalamus are neurons expressing neuropeptide Y, proopiomelanocortin and gonadotropin-releasing hormone, but the presence of leptin receptors in peripheral reproductive structures suggests that leptin might also act at these sites. Human obesity is often associated with reproductive disturbances. The situation in humans is more complex than in the animal models of leptin deficit and the presence of leptin resistance in these subjects is suggested. In conclusion, leptin fits many requirements for a molecule linking the regulation of energy balance and the control of reproduction.
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PMID:Leptin: a possible link between food intake, energy expenditure, and reproductive function. 1102 65

In mammals, the function of the reproductive system is dependent on the availability of energy in the environment. It is well established that acute modifications of energy balance modulate the hypothalamic-pituitary-gonadal axis. In several species, fasting and caloric restriction have been shown to cause the suppression of pulsatile luteinizing hormone secretion, via an inhibition of the gonadotropin-releasing hormone pulse generator. Such a mechanism probably prevents energy being wasted for reproduction. By contrast, excessive energy storage and obesity interfere with the correct regulation of the reproductive axis. The identification of leptin and leptin receptors, along with studies performed in animal models of leptin deficiency and resistance, has focused attention on the role of this molecule in reproduction, and disclosed new aspects of the relationship between energy stores, adipose tissue and reproductive function. Here, we discuss the central and peripheral effects of leptin on reproductive tissues, and try to fit a complex reality into a simplified model. In particular, the roles of leptin in reproduction at different anatomical levels and in various clinical and experimental settings are discussed.
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PMID:Leptin in reproduction. 1116 24

Mutations in the melanocortin-4 receptor (MC4-R) cause obesity in both mice and humans, and the receptor is presumed to have an important role in the regulation of energy homeostasis. The MC4-R is expressed in discrete sets of neurons in the central nervous system, and thus it has been technically difficult to study the regulation of expression and the signaling mechanisms of this receptor. We report here a neuronal cell line that exhibits endogenous functional expression for the MC4-R. Initially, RT-PCR analysis showed the presence of MC4-R RNA in the hypothalamic GT1-1 and GT1-7 cells. In addition, GT1-7 cells expressed melanocortin-3 receptor while the GT1-1 subclone specifically expressed predominantly the MC4-R RNA. High-affinity binding sites were demonstrated in the GT1-1 and GT1-7 cells for NDP-alpha melanocyte-stimulating hormone (MSH; K(i) = 1.1 x 10(-10) and 1.8 x 10(-10) M) and agouti-related protein (AGRP; K(i) = 1.548 x 10(-9) and 1.663(-9) M). alpha-MSH-stimulated cAMP production in GT1-1 cells with an EC(50) of 2.2 x 10(-8) M, and cAMP production was inhibited in the presence of AGRP, an endogenous antagonist of the MC4-R. Stimulation of gonadotropin-releasing hormone (GnRH) secretion was achieved with 1 nM to 1 microM concentrations of NDP-alpha-MSH while no GnRH secretion was observed when the GT1-1 cells were treated with AGRP. The data presented here show that GT1-1 cells specifically express a functional MC4-R that couples to GnRH release.
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PMID:Expression of functional melanocortin-4 receptor in the hypothalamic GT1-1 cell line. 1152 21


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