Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we evaluated the subpopulation of lymphoid cells from normal and hypophysectomized rats producing GH and IGF-I in vitro. The data show that removal of the pituitary results in depression of GH production in spleen, thymus, and bone marrow and an increase in the peripheral blood leukocytes. The changes in the percentage of cells producing GH in hypophysectomized animals are not due to a single cell type but appears to influence the T-helper, T-cytotoxic, and B-cell subsets. Interestingly, no significant changes in the levels of GH RNA were detected between control and hypophysectomized animals after the in vitro culture. We also found that the increase in GH production in spleen cell cultures after mitogen stimulation could be accounted for by an increase in the percentage of T cells producing GH. Lastly, we demonstrated that the cells positive for GH production were also positive for IGF-I production. This later finding coupled with our previous results suggest that an autocrine regulatory circuit may be important for the production of leukocyte-derived irGH and irIGF-I within the immune system.
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PMID:The production of growth hormone and insulin-like growth factor-I by the same subpopulation of rat mononuclear leukocytes. 149 30

Long lasting intensive physical exercise leads to growth retardation. Short-limbed girls are selected for the training as gymnasts. In a preliminary study with 9 gymnasts a significant decrease of the IGF-I concentration was found after intensive 3-day exercise. This experiment was repeated with 16 girls (11.7 +/- 0.8 years old). The higher the initial DHEA-S and E2 concentration of the gymnasts, the higher were the IGF-I basal levels. The intensive training resulted in the following changes (basal after exercise): IGF-I: 247 +/- 86-->188 +/- 77 ng/ml, T3: 2.4 +/- 0.4-->2.1 +/- 0.3 nmol/l, T4: 96 +/- 15-->98 +/- 19 nmol/l, DHEA-S: 930 +/- 636-->1018 +/- 701 nmol/l, testosterone: 1.5 +/- 0.3-->1.9 +/- 0.4 nmol/l, cortisol: 824 +/- 272-->799 +/- 219 nmol/l. During the 3-day intensive training, the parallel decrease of IGF-I and T3 concentrations in each sportswomen is particularly impressive. Apart from the sequelae of 'negative' selection, the low T3-syndrome, the anti-insulin effect of high GH secretion and the elevated cortisol concentration are responsible for the growth depression, retardation in bone age and the higher incidence of skeletal problems in these gymnasts with 'exercise-induced' delay in development.
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PMID:Influence of intensive exercise on insulin-like growth factor I, thyroid and steroid hormones in female gymnasts. 184 68

Dietary nitrate significantly inhibits the growth of male and female rats. To test the possibility that the growth hormone-releasing factor (GRF) content in hypothalamic tissue is deranged under these conditions, male and female rats were fed a diet containing 3% KNO3 for 6 weeks, compared to a normal diet (4 X 5 animals). The food intake of rats fed nitrate was reduced significantly (23 and 28% resp.). Weight gain was also decreased by 35 and 41% in male and female rats. The mean Sm-C/IGF-I concentration was 1.61 and 1.03 rU/ml in male and female control rats, whereas the concentrations in nitrate-exposed rats were 0.92 and 0.64, respectively (P less than 0.01). The GRF content of hypothalamic tissue also decreased significantly from 407 and 533 ng/g protein in controls to 174 and 229 in treated male and female rats. Nitrate exposure is characterized by hypothyroidism, food intake depression, low Sm-C/IGF-I concentrations in plasma and a decreased hypothalamic GRF content. Independent of the peripheral changes, the content of Sm-C/IGF-I in the brain remains constant. The results of the study demonstrate that thyroid hormone deficiency leads to an inhibition of GH axis already at the hypothalamic level.
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PMID:Nitrate-induced hypothyroidism is associated with a reduced concentration of growth hormone-releasing factor in hypothalamic tissue of rats. 186 11

To explore the role of the somatomedin-mediated long-loop negative feed-back mechanism in altered growth hormone (GH) secretory dynamics associated with depression, plasma IGF-I concentrations were measured in 34 patients with a major depressive episode and matched healthy subjects. Compared with controls, depressed patients exhibited significantly increased plasma IGF-I concentrations. In the patient group plasma IGF-I concentrations were positively correlated with the maximum post-dexamethasone plasma cortisol concentrations. Our data suggest that increased plasma IGF-I concentration may reflect diurnal GH hypersecretion, contribute to deficient GH responses to dynamic challenges, and indicate an interrelationship between the hypothalamic-pituitary-somatotropic (HPS) and -adrenocortical (HPA) system regulation in depression.
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PMID:Insulin-like growth factor I in depressed patients and controls. 322 25

The effect of long- and short-term manipulations of uterine blood flow on fetal plasma levels of IGF-I and -II have been studied in sheep at days 125-139 of pregnancy and compared with those in near term rats and guinea pig. The primary objective is to show that both long- and short-term reduction of uterine blood flow is associated with increase in the fetal plasma concentration of IGF-II while that of IGF-I falls. In the pregnant sheep long-term depression of utero-placental blood flow was caused by surgical reduction in placental mass (carunclectomy) prior to conception. This reduced fetal weight to 2.42 +/- 0.49 kg (SD) compared with 3.41 +/- 0.46 in controls; the respective values for uterine blood flow being 1694 +/- 558 and 913 +/- 324 ml/min respectively. This was associated with a fall in fetal plasma IGF-I concentration from 22.6 +/- 3.4 ng/ml to 14.9 +/- 1.31 ng/ml and a rise in IGF-II from 1952 +/- 284 ng/ml to 3360 +/- 914 ng/ml respectively. Similar changes in the plasma concentrations of IGF peptides were observed in fetal rats and guinea pigs in response to uterine artery ligation. Short-term reduction (60 min) of the uterine blood flow was caused either by compression of the common uterine artery to depress flow from 1491 +/- 375 to 648 +/- 216 ml/min or through intraarterial infusion of adrenaline at 35 ug/min to lower flow from 1628 +/- 339 to 1195 +/- 128 ml/min. Such falls in uterine blood flow had no significant effect on fetal plasma IGF-I levels but increased IGF-II levels by 30 to 60%.
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PMID:Studies on the growth of the fetal sheep. Effects of surgical reduction in placental size, or experimental manipulation of uterine blood flow on plasma sulphation promoting activity and on the concentration of insulin-like growth factors I and II. 339 9

The effects of prenatal growth restriction caused by uterine artery ligation at midgestation has been studied in pregnant guinea pigs. Ligation of a uterine artery at day 30 of pregnancy commonly caused a reduction in fetal growth of greater than 45% by days 40-65 of gestation. This was associated with substantial delays in the development of a number of fetal tissues and in particular that of the skeleton which remained cartilagenous for longer than normal. Hence normally by day 50 of pregnancy clear evidence of epiphyseal ossification in the long bones of the fore- and hindlimbs was present, but in growth retarded fetuses of less than 50% of normal size such evidence was sparce. Delayed skeletal development and the slowing of fetal growth rate correlated well with marked depression of plasma sulphation-promoting activity. Indeed plasma from fetuses that were less than 40% of normal size inhibited sulphate incorporation into pig costal cartilage. This indicated the presence of inhibitory factors in the plasma of such fetuses, an interpretation that was re-inforced by the observation that plasma IGF-II concentrations were 2-4 times above normal. In contrast plasma IGF-I concentration was depressed upto 50% by growth retardation in line with the fall in fetal plasma insulin concentration. The changes in plasma sulphation-promoting activity and of IGF-I are consistent with slowing of DNA, RNA and protein synthesis and of gene expression in tissues of the growth-retarded fetus. The elevated fetal plasma IGF-II concentration provided further evidence that in the fetal guinea pig this hormone has a potentially glyconeogenic action and maintains essential glycogen stores.
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PMID:Studies on the growth of the fetal guinea pig. Effects of reduction in uterine blood flow on the plasma sulphation-promoting activity and on the concentration of insulin-like growth factors-I and -II. 359 51

The present study examined the effects of dexamethasone on mucosal adaptation after massive small bowel resection. Rats underwent 80% jejunoileal resection or a sham operation and received either vehicle or 128 micrograms.kg-1.day-1 sc dexamethasone for 7 days. Dexamethasone infusion resulted in decreased weight, DNA content, and protein content in the duodenojejunal and ileal mucosa in both sham and resected rats. Sucrase, lactase, and maltase activities (all in mumol.g protein-1.min-1) in the duodenojejunal mucosa were elevated by dexamethasone infusion. By contrast, enzyme activities were elevated only in the ileal mucosa of dexamethasone-infused sham-operated rats compared with sham-operated control rats, and dexamethasone did not elevate enzyme activities in resected rats. We further examined whether the inhibitory effects of dexamethasone on mucosal adaptation may be related to changes in either insulin-like growth factor (IGF) or IGF binding protein (BP) serum levels. Serum IGF-I and IGF-II levels were markedly decreased in dexamethasone-infused resected and sham-operated rats. IGF BP-1 serum levels were elevated by dexamethasone treatment with a concomitant depression in serum IGF BP-2 levels. IGF BP-3 levels were lowered by dexamethasone treatment in sham-operated rats and by gut resection, and serum IGF BP-4 levels did not change. These results suggest that the growth-inhibiting effects of dexamethasone in small intestinal mucosa may be partially mediated by decreased serum IGF levels or by alterations in IGF activity associated with changes in serum levels of IGF BPs.
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PMID:Dexamethasone inhibits mucosal adaptation after small bowel resection. 751 28

The influence of the activities of daily living on human growth hormone (hGH) release and plasma insulin-like growth factor (IGF-I) levels is not known. Individuals with spinal cord injury (SCI) and paralysis generally have reduced levels of activity compared with ambulatory subjects. We studied sixteen subjects with SCI and sixteen nonSCI subjects matched for age, gender and body mass index (BMI) as controls. After an intravenous infusion of arginine hydrochloride (30 g/subject over 30 minutes), mean plasma hGH values at 30 and 60 minutes were significantly lower in the group with SCI compared with the control group (3.4 +/- 0.7 versus 10.7 +/- 2.5 ng/ml, p < 0.01; and 5.2 +/- 1.5 versus 12.5 +/- 2.7 ng/ml, p < 0.05). Also, peak and sum hGH responses were significantly lower in the group with SCI than in the control group (5.8 +/- 1.5 versus 14.1 +/- 2.8 ng/ml, p < 0.01; and 15.2 +/- 3.1 versus 34.8 +/- 7.2 ng/ml, p < 0.02). Controlling for age and BMI, the results remained significant. However, the mean plasma IGF-I level was significantly lower in SCI subjects younger than 45 years old than in the similar subgroup of age-restricted controls (202 +/- 19 versus 324 +/- 27 ng/ml, p < 0.05), whereas, a comparison of subgroups of subjects 45 years or older did not reveal a significant difference. These findings support the hypothesis that decreased daily physical activity results in depression of the hGH/IGF-I axis in younger individuals with SCI and may be considered to be a state of premature aging.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blunted growth hormone response to intravenous arginine in subjects with a spinal cord injury. 800 64

IGF-I analogues that bind poorly to IGFBPs are substantially more potent than IGF-I at stimulating growth in rats. However, rodents differ from other mammals because they contain only minimal circulating levels of IGF-II and they are poorly responsive to GH. In this report we review a series of experiments carried out in pigs, a species that is both GH responsive and has high blood concentrations of IGF-II. Intravenous bolus administration of IGFs to 55 kg pigs depressed blood glucose with the potency greatest for analogues such as des (1-3) IGF-I, R3IGF-I and Long R3IGF-I that showed the weakest binding to pig IGFBP-3, a similar efficacy pattern to that reported in the rat. Chronic subcutaneous administration of Long R3IGF-I, however, reduced growth rates, led to a depression in food intake and lowered concentrations of IGF-I, IGF-II and IGFBP-3. IGF-I itself depressed IGF-II concentrations and did not stimulate growth. Subcutaneous infusion of IGFs over a 3-day period, also in 55 kg pigs, demonstrated that analogues that bound least well to IGFBP-3 were the most effective at reducing the concentration of this binding protein, suggesting that the inhibition of growth was related to the depression of IGFBP-3. On the other hand, IGF-I and Long R3IGF-I increased growth rats in neonatal pigs, especially under conditions of reduced food intake. As these anabolic effects occur at a developmental stage where the animals are insensitive to GH in a manner analogous to the situation in rats, it is plausible that the feed-back inhibition of GH secretion explains the catabolic response to IGFs in older pigs.
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PMID:In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. 881 82

Several studies support the idea that the polypeptides belonging to the family of insulin and insulin-like growth factors (IGFs) play an important role in brain development and continue to be produced in discrete areas of the adult brain. In numerous neuronal populations within the olfactory bulb, the cerebral and cerebellar cortex, the hippocampus, some diencephalic and brainstem nuclei, the spinal cord and the retina, specific insulin and IGF receptors, as well as crucial components of the intracellular receptor signaling pathway have been demonstrated. Thus, mature neurons are endowed with the cellular machinery to respond to insulin and IGF stimulation. Studies in vitro and in vivo, using normal and transgenic animals, have led to the hypothesis that, in the adult brain, IGF-I not only acts as a trophic factor, but also as a neuromodulator of some higher brain functions, such as long-term potentiation and depression. Furthermore, a trophic effect on certain neuronal populations becomes clearly evident in the ischemic brain or neurodegenerative disorders. Thus, the analysis of the early intracellular signaling pathway for the insulin/IGF receptor family in the brain is providing us with new intriguing findings on the way the mammalian brain is sculpted and operates.
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PMID:The early intracellular signaling pathway for the insulin/insulin-like growth factor receptor family in the mammalian central nervous system. 893 49


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