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

The pharmacokinetic profile of recombinant human insulin-like growth factor I (IGF-I) was studied in healthy volunteers. Following a single subcutaneous injection of 40 micrograms/kg or 80 micrograms/kg, mean serum IGF-I concentrations increased by 150 ng/ml and 245 ng/ml, respectively. During repeated daily injections of 40 micrograms/kg, a steady-state IGF-I level of 150 ng/ml above baseline was reached. Of the pharmacokinetic indices measured, only Tmax varied between single and multiple dose regimens (6.9 hours versus 3.5 hours). No hypoglycaemic symptoms were observed, and after injection of IGF-I no depression of endogenous IGF-I production was observed. Fasting insulin levels were unaltered, but postprandial insulin was lowered by IGF-I with respect to placebo.
 ...
PMID:Pharmacokinetic profile of recombinant human insulin-like growth factor I given subcutaneously in normal subjects. 178 5

In order to evaluate the possible effect of glucocorticoids as neuromodulators of the hypothalamic-pituitary-somatotropic system in depression, cortisol, growth hormone (GH), and insulin-like growth factor I (IGF-I) concentrations were studied before and after oral administration of 1 mg dexamethasone at 11 p.m. in 16 patients during depression and after recovery and in 28 healthy controls. While there were no significant differences in GH and IGF-I levels between depressed, recovered and control subjects, GH and IGF-I concentrations of cortisol non-suppressors were significantly elevated compared to suppressors. Moreover, post-dexamethasone cortisol, GH, and IGF-I levels were positively correlated. Dexamethasone had a stimulating effect on GH and IGF-I values in patients during depression and in cortisol non-suppressors only; this effect was absent in recovered and in control subjects and in cortisol suppressors. Thus, hypercortisolemia may be of great importance for the dysregulation of the hypothalamic-pituitary-somatotropic system reported in depression.
 ...
PMID:Effects of glucocorticoids on the regulation of the hypothalamic-pituitary-somatotropic system in depression. 252 80

The study described here investigates the influence of a specific alimentary Zn deficiency on the concentration of growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin in the serum of force-fed rats. For this purpose 24 male Sprague-Dawley rats with an average bodyweight of 108 g were divided into 2 groups of 12 animals each. The Zn-deficient group and the control group received for 12 days a semi-synthetic casein diet with a Zn content of 1.3 and 25 ppm respectively. In order to prevent the reduced feed intake which occurs in Zn deficiency and the associated energy and protein shortage from interfering with the experimental parameters, all animals were fed 4 times daily by gastric tube. This made it possible to supply all animals with adequate-nutrients and to synchronise the feed intake exactly. After 12 days the depleted rats were in a severe state of Zn deficiency, as demonstrated by the reduction of Zn in the serum and the femur by 62% and 44% respectively and the 70% lower serum activity of alkaline phosphatase. In the Zn-deficient rats the concentration of GH in the serum was significantly increased by 78%, while IGF-1 and insulin were significantly reduced by 28% and 25% respectively. It is thought that the growth depression observed in the Zn-deficient rats in this study despite their identical feed intake is probably due to a reduced concentration of IGF-I and insulin and that the biological activity or the binding of GH to receptors is impaired in specific alimentary Zn deficiency.
 ...
PMID:Influence of alimentary zinc deficiency on the concentration of growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin in the serum of force-fed rats. 783 22

The objective of this study was to determine whether growth-depressant effects of lead (Pb) could be prevented by preventing the accompanying depression of caloric intake from ad libitum food consumption by caloric supplementation. The animal used was the female weanling rat. Three experiments were performed in which progressively increasing levels of caloric supplementation were provided in order to attain a level of nutrition which would totally prevent growth depression from Pb exposure. Nutritional supplementation of Pb-exposed animals almost completely eliminated the Pb-induced depression of weight gains. We conclude that the deficit in growth due to Pb can be adequately explained on the basis of a primary effect on appetite, rather than being secondary to depression of proliferative responses of cells to growth factors, e.g., insulin-like growth factor I.
 ...
PMID:Effects of supplemental nutrition on lead-induced depression of growth and food consumption in weanling rats. 787 81

Conflicting data have been reported on the psychosexual impact of hysterectomy combined with bilateral oophorectomy. Three age-matched, hysterectomized groups of women were investigated: Group A (n = 33): oophorectomized, not receiving estrogen replacement therapy (ERT); Group B (n = 33): oophorectomized, receiving ERT; and Group C (n = 35): ovaries preserved and not receiving ERT. The McCoy Sexual Rating Scale and the Psychological General Well-Being Index as well as a semi-structured interview were used to assess postoperative experience with respect to libido, vaginal lubrication, ability of getting pleasure from intercourse, and ability to achieve orgasm. Serum concentrations of total and free testosterone, insulin-like growth factor I (IGF-I), sex hormone binding globulin, dehydroepiandrosterone sulfate and 4-androstene-3,17-dione were determined. In oophorectomized women sexual life was impaired as compared to those with intact ovaries and these women complained about less pleasure from coitus, impaired libido and lubrication. Regardless of whether estrogens were administered or not a similar pattern was found, indicating that estrogens are of little value in treating these specific sexual dysfunctions. Oophorectomized women receiving ERT reported less anxiety and depression and more well-being similar to women whose ovaries had been preserved. No correlation was found between psychosexual variables and biochemical androgen markers. However, the IGF-I levels were strongly correlated to sexual activity and responsiveness.
 ...
PMID:Elective ovarian removal and estrogen replacement therapy--effects on sexual life, psychological well-being and androgen status. 814 82

We tested the possibility that insulin-like growth factor I (IGF-I) acts as a neuromodulator in the adult cerebellar cortex since previous observations indicated that IGF-I is located in the olivo-cerebellar system encompassing the inferior olive and Purkinje cells. We found that conjoint administration of IGF-I and glutamate through a microdialysis probe stereotaxically implanted into the cerebellar cortex and deep cerebellar nuclei greatly depressed the release of gamma-aminobutyric acid (GABA), which normally follows a glutamate pulse. This inhibition was dose-dependent and long-lasting. Moreover, the effect was specific for glutamate since KCl-induced GABA release was not modified by IGF-I. Basic fibroblast growth factor, another growth-related peptide present in the cerebellum, did not alter the response of GABA to glutamate stimulation. In addition, electrical stimulation of the inferior olivary complex significantly raised IGF-I levels in the cerebellar cortex. Interestingly, when the inferior olive was stimulated in conjunction with glutamate administration, GABA release by cerebellar cells in response to subsequent glutamate pulses was depressed in a manner reminiscent of that seen after IGF-I. These findings indicate that IGF-I produces a long-lasting depression of GABA release by Purkinje cells in response to glutamate. IGF-I might be present in climbing fiber terminals and/or cells within the cerebellar cortex and thereby might affect Purkinje cell function. Whether this IGF-I-induced impairment of glutamate stimulation of Purkinje cells underlies functionally plastic processes such as long-term depression is open to question.
 ...
PMID:Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I. 834 60

To determine whether growth hormone (GH) replacement improves cardiac function, GH-deficient hypophysectomized rats with moderate myocardial infarction (MI) were studied after 3 wk of treatment with either recombinant rat GH (3.2 mg.kg-1.day-1 sc) or vehicle. The serum insulin-like growth factor I level in rats after GH treatment was approximately 10-fold greater than in vehicle-treated rats. GH replacement prevented a decrease in body weight at 1 wk (+5 +/- 6 vs. -26 +/- 4 g in vehicle group, P < 0.01) and increased body weight at 3 wk (+40 +/- 5 vs. -30 +/- 4 g in vehicle group, P < 0.01) after MI. Infarct size, expressed as a percentage of left ventricular (LV) perimeter, was similar for GH-treated (21 +/- 3%) and vehicle-treated (23 +/- 3%) rats. Basal LV systolic pressure, LV end-diastolic pressure, LV dP/dt, mean arterial pressure and heart rate, and the changes in these parameters in response to isoproterenol and norepinephrine were similar for these two groups. Although GH replacement tended to prevent depression in myocardial contractility during the recovery period after maximal stimulation either by the largest dose of isoproterenol (0.8 microgram/kg iv) or by acute volume loading, differences between the two groups were not statistically significant. In addition, to determine the effects of excess GH treatment in a severe state of cardiac dysfunction, nonhypophysectomized rats with larger infarcts (i.e., > 45% of the LV) were studied after 4 wk of treatment. There were no differences either in hemodynamic indexes or in infarct size between the GH- and vehicle-treated groups, whereas body weight had increased (P < 0.01) in the GH-treated group. Thus, although GH treatment effectively prevents the loss of body weight after MI, neither GH replacement nor excess GH treatment plays an important role in preserving cardiac function in rats with moderate or large MI.
 ...
PMID:GH replacement fails to improve ventricular function in hypophysectomized rats with myocardial infarction. 894 83

We determined the dose-dependent effects of central mu-opioid receptor stimulation on rates of tissue protein synthesis. Chronically catheterized conscious rats received an intracerebroventricular injection of [D-Ala2, N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.5, 2, or 8 nmol/rat) or water (5 microliters) 45 min before determination of protein synthesis by the flooding dose technique. DAGO produced a significant decrease in tissue protein synthesis in liver (57%), spleen (54%), gut mucosa (36%), gut serosa (23%), kidney (48%), gastrocnemius (33%), and plantaris muscle (27%), but it did not alter rates of protein synthesis in the brain, heart, and soleus muscle. DAGO produced an acute dose-dependent respiratory depression 30 min after intracerebroventricular injection; this depression resulted in acidosis, hypoxia, and hypercapnia (pH 7.19 +/- 0.04, arterial partial O2, pressure 44.2 +/- 3.4 Torr, arterial O2 saturation 65.3 +/- 5.5%, and PCO2 66.3 +/- 4.4 Torr). Intracerebroventricular DAGO increased circulating levels of catecholamines, corticosterone, and growth hormone but did not alter those of insulin and insulin-like growth factor I. Significant positive correlations between protein synthesis and pH were observed in the tissues studied (i.e., liver protein synthesis vs. pH, P < 0.0001, r = 0.902; gastrocnemius protein synthesis vs. pH, P < 0.0001, r = 0.830). Our results indicate that mu-receptor stimulation inhibits tissue protein synthesis, and this effect appears to be secondary to respiratory depression and the resulting acidosis and/or hypoxia. Furthermore, our findings suggest differential sensitivity in tissue response to alterations in pH, hypoxia, and stress hormone elevation.
 ...
PMID:Central opiate mu-receptor-mediated suppression of tissue protein synthesis. 932 68

To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 +/- 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW.day), IGF-I (0.015 mg/kg BW.day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 +/- 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 +/- 1.8 and 8.4 +/- 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.
 ...
PMID:Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women. 958 42

Dietary protein deficiency, common in elderly, is associated with decreased areal bone mineral density and plasma insulin-like growth factor I (IGF-I). To investigate the early adaptation of bone cells to protein restriction, 6-month-old female rats were pair-fed with isocaloric 15% (control) or 2.5% casein diets for 14 days. Animals were then treated daily with rhIGF-I/IGFBP-3 (1:4, 2.5 mg IGF-I/kg BW) or with vehicle for 10 days. After double-labeling, proximal metaphysis and mid-diaphysis of the tibia were analyzed histomorphometrically. Plasma osteocalcin, IGF-I, and urinary deoxypyridinoline were quantified. After 14 days of protein restriction, significant drops in plasma osteocalcin (13%) and IGF-I (37%), in periosteal formation (83%) and mineral apposition (49%) rates are observed, indicating a decreased osteoblast recruitment and activity. In cancellous bone, a significant decrease in active eroded surfaces (27%) and osteoclast number (24%) indicates a transient depression of resorption. In rats fed the 15% casein diet, rhIGF-I/IGFBP-3 increases cancellous (42%) and periosteal (600%) formation rates, indicating an increased osteoblast recruitment. In protein-restricted rats, rhIGF-I/IGFBP-3 fails to increase cancellous or periosteal bone formation and plasma osteocalcin is significantly lower than in 15% casein+rhIGF-I/ IGFBP-3 rats. Protein restriction induces osteoblast resistance to rhIGF-I/IGFBP-3 in both bone envelopes. Low plasma IGF-I and osteoblast resistance to IGF-I, may contribute to the impaired periosteal formation.
 ...
PMID:Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I), impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in adult female rats. 1096 85


1 2 Next >>