UMLS:C0432222 - FACTA Search

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Query: UMLS:C0432222 (SEM)
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The objective of this study was to determine the presence, regulation, and localization of specific receptors for insulin-like growth factor I (IGF-I) in primate reproductive tissues. Uteri were obtained from baboons either during the menstrual cycle, after ovariectomy with or without steroid treatments, or during early pregnancy (Days 18-60 postovulation [PO]). Placental and decidual tissues were collected from baboons during late pregnancy (Days 130-160). Localization of type I IGF receptor was determined by indirect immunocytochemistry (alpha IR3 antibody), and levels of type I IGF receptors were determined by affinity cross-linking and binding assays. Specific staining for type I IGF receptors was present in the membranes of glandular epithelial cells throughout the cycle and early pregnancy; however, there was a decrease in staining intensity by the late luteal phase and also throughout early pregnancy compared to the late follicular phase. Specific receptor staining was absent in stromal cells throughout the cycle. By Day 19 PO, stromal cells directly under the trophoblast were positive for type I IGF receptor, and an increase in stromal staining at the implantation site was observed as pregnancy proceeded. Stromal staining was apparent in non-implantation site tissue by Day 32 PO. Some placental villi showed positive receptor staining as early as on Day 18 PO, and an increase in the number of positive villi was apparent as pregnancy progressed. An 125I-IGF-I-protein complex of approximately 140,000 daltons, corresponding to the alpha subunit of the type I IGF receptor, was detected in endometrial, placental, and decidual membranes. The intensity of this signal was high in endometrium from the follicular phase, whereas low levels were detected in endometrium from the luteal phase. Throughout early pregnancy, alpha receptor subunit was present in placental and decidual membranes; alpha receptor subunit increased in placenta as pregnancy proceeded. An additional 125I-IGF-I-protein complex of 43,000 daltons, corresponding to IGF binding protein-1 (IGFBP-1), was present in decidual membranes and appeared to increase as pregnancy proceeded. Specific binding of 125I-IGF-I to placental membranes was displaced by unlabeled IGF-I and alpha IR3 antibody, whereas both unlabeled IGF-I and IGF-II competed equally for binding to decidual membranes. Scatchard analysis of 125I-IGF-I binding to placental membranes revealed a single class of high-affinity receptors (KD = 2.35 +/- 0.8 nM; mean +/- SEM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization, localization, and regulation of receptors for insulin-like growth factor I in the baboon uterus during the cycle and pregnancy. 819 60

The objectives were to investigate whether insulin-dependent diabetes mellitus disrupts production of estradiol and activity of the insulin-like growth factor (IGF)-I system in individual ovarian follicles during the preovulatory period of the estrous cycle. Diabetes mellitus was induced with streptozocin (150 mg/kg) in seven cyclic gilts at 180 +/- 5 days of age. On Day 12 of the estrous cycle, insulin replacement therapy was withdrawn from three gilts and continued in four; four gilts served as normal controls. After ovary removal on Day 18, all follicles > or = 3 mm diameter were dissected free and cultured for 6 h in the presence of 280 ng testosterone for assessment of estradiol and IGF-I production and binding protein activity. Treatments did not affect corpora lutea number (15.4 +/- 0.8) or serum estradiol (5.8 +/- 0.8 pg/ml) on Day 18. There were no differences for any measure of follicular development between normal and insulin-treated diabetic gilts. Untreated diabetic gilts, compared to normal and insulin-treated diabetic gilts, had fewer total visible follicles (22.7 vs. 61.3 and 63.3; SEM = 8; p < 0.01) and reduced follicular diameter (3.4 vs. 4.4 and 4.2 mm; SEM = 0.3; p < 0.0001), respectively. Untreated diabetic gilts had a greater percentage of macroscopically atretic follicles than normal and insulin-treated diabetic gilts (75% vs. 47% and 36%; SEM = 10; p < 0.05). Untreated diabetes mellitus lowered estradiol (p < 0.01); however, effects of treatment on estradiol production were not significant when diameter was part of statistical models. When contents of IGF-I in follicular fluid and conditioned medium were summed after 6 h of culture, untreated diabetic pigs had lower IGF-I at all follicle diameters than pigs in the other treatments (p < 0.05). IGF binding protein (BP) activity was affected by diabetes mellitus, with untreated diabetic pigs having greater IGFBP-1 activity in medium and with both diabetic groups having greater IGFBP-2 activity in follicular fluid (p < 0.05). Activity of IGFBP-1 predominated in conditioned medium, and IGFBP-2 activity predominated in follicular fluid. IGFBP-3 was decreased in follicular fluid of atretic follicles and in medium of atretic follicles in all except the insulin-treated diabetic gilts; in these gilts it was increased in atretic follicles (treatment by atresia interaction; p < 0.05). In conclusion, estradiol was most related to size of the follicle; however, lowering of IGF-I regardless of follicle diameter and alterations in IGFBP activity suggest that diabetes affects IGF-I and its binding proteins differently from estradiol production. These alterations may explain reduced follicular growth and increased follicular atresia in diabetic pigs.
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PMID:Depletion of insulin in streptozocin-induced-diabetic pigs alters estradiol, insulin-like growth factor (IGF)-I and IGF binding proteins in cultured ovarian follicles. 887 89

The aim of this study was to investigate the influence of hemodialysis on insulin-like growth factor-I (IGF-I) and the IGF binding proteins (IGFBPs) in patients with end-stage renal disease (ESRD). IGF-I and IGF-II circulate bound to IGFBPs which are known to influence the IGF-I bioavailability. Ten ESRD patients were studied before and after hemodialysis on low flux filters. IGF-I, insulin and IGFBP-I were measured by specific RIAs, and IGFBP-2 and IGFBP-3 were quantified by densitometry after Western ligand blotting. Diurnal curves of IGFBP-1 were performed in two additional patients. Before dialysis, the mean (+/- SEM) IGF-I level was 202.2 +/- 12.1 micrograms/l corresponding to a SD-score of 1.8 +/- 0.3. Basal IGFBP-1 was increased 2-fold compared to normal levels (82.4 +/- 24.1 micrograms/l) and increased further during hemodialysis to 118.1 +/- 28.5 micrograms/l (P < 0.007). The mean increase during dialysis in IGFBP-1 was 74 +/- 24%. Predialysis IGFBP-2 was increased to 184.8 +/- 32.5% of the reference serum and was not significantly changed by dialysis. The predialysis IGFBP-3, 38.5 kDa band was within normal levels 90.1 +/- 18.8% of the reference serum while the IGFBP-3, 41.5 kDa band was decreased to 62.4 +/- 11.3% of the reference serum. Both IGFBP-3 bands were not significantly changed after dialysis. The mean basal insulin level was high, 38.2 +/- 3.0 mU/L, in spite of normal glucose levels suggesting insulin resistance. The mean values of IGF-I, insulin and glucose were unchanged after dialysis. The ratio between IGF-I and IGFBP-1 decreased significantly after dialysis to 53% of the ratio before dialysis (P < 0.005). The ratio between IGF-I and IGFBP-2 or IGFBP-3 did not change after dialysis. The circadian variation of IGFBP-1 during dialysis days was impaired with a delayed decrease of IGFBP-1 compared to the non-dialysis day. In ESRD patients predialysis mean values of insulin, IGF-I SD-score, IGFBP-1 and IGFBP-2 were increased, while the mean densitrometric values of the IGFBP-3 bands on Western ligand blot were either normal or reduced. IGFBP-1 was raised significantly with a mean of 74% after dialysis, the predialysis level was more than 2-fold elevated with impaired circadian variation of IGFBP-1 on dialysis days. High levels of IGFBPs may bind free IGF-I and decrease IGF-I bioavailability thus contributing to the catabolism associated with dialysis.
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PMID:Decreased bioavailability of insulin-like growth factor-I, a cause of catabolism in hemodialysis patients? 889 46

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.
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PMID:Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults. 902 11

Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone in 27 transplanted patients aged 3.1-20 years. Methylprednisone (mean +/- SEM 0.17 +/- 0.01 mg/kg per day) was replaced by deflazacort (0.29 +/- 0.01 mg/kg per day) for a period of 1-5 years. Calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 2.6 +/- 0.5 cm/year to 5.2 +/- 0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein-3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation.
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PMID:Effects of deflazacort immunosuppression on long-term growth and growth factors after renal transplantation. 920 81

To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)2D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2 1/2 days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)2D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 microg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean +/- SEM. Whereas serum 1,25(OH)2D (58.9 +/- 7.7 versus 51.6 +/- 7.4 pg/ml, P< 0.01), serum phosphorus (4.5 +/- 0.1 versus 3.7 +/- 0.1 mg/dl, P < 0.01), TRP (92.0 +/- 0.5 versus 87.8 +/- 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 +/- 0.1 versus 3.5 +/- 0.2, P < 0.005), and urinary calcium (602 +/- 49 versus 346 +/- 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 +/- 1.9 versus 26.8 +/- 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(oh)2D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)2D.
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PMID:Increased serum 1,25-dihydroxyvitamin D after growth hormone administration is not parathyroid hormone-mediated. 931 96

Hexarelin, a powerful GH-releasing peptide, is capable of causing profound GH release in normal subjects after oral, intranasal, i.v., and s.c. administration. The effect of long-term administration on GH levels in adults is unknown. We have, therefore, assessed the effects of 16 weeks of twice-daily s.c. hexarelin therapy (1.5 micrograms/kg BW) on the GH response to a single injection of hexarelin, and also the GH response to hexarelin 4 weeks after cessation of hexarelin therapy. We have also assessed the effects of chronic hexarelin therapy on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of bone formation (osteocalcin, procollagen-type-III-N-terminal-peptide, and C-terminal propeptide of type I collagen), and resorption (urinary deoxypyridinoline and pyridinoline), body composition, and bone mineral density. The mean (+/- SEM) area under the GH curve (AUCGH) at weeks 0, 1, 4, 16, and 20 were 19.1 +/- 2.4 micrograms/L.h, 13.1 +/- 2.3 micrograms/L.h, 12.3 +/- 2.4 micrograms/L.h, 10.5 +/- 1.8 micrograms/L.h, and 19.4 +/- 3.7 micrograms/L.h, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUCGH at week 4 and week 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUCGH increased significantly, compared with AUCGH at week 16 (P < 0.05), and was not significantly different from that at week 0. Serum IGF-I and IGF binding protein-3 did not change significantly over the 20-week period (P = 0.24 and P = 0.74, respectively). Of the bone markers measured, only serum C-terminal propeptide of type I collagen changed significantly and was higher at week 16, compared with baseline (P = 0.019). Total body fat, lean body mass, and bone mineral density had not changed significantly at week 16, compared with baseline (P = 0.6, P = 0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin. In the present study, the biological impact of this hexarelin schedule on the GH-IGF-I axis seems to be minimal. The therapeutic potential of chronic hexarelin requires further investigation.
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PMID:Growth hormone status during long-term hexarelin therapy. 958 71

We compared the effects of exogenous insulin and porcine ST (pST) on follicular development after weaning. Crossbred primiparous sows received saline (1.5 mL i.m.; n = 9), insulin (.4 IU/kg BW s.c.; Eli Lilly Lente Iletin II; n = 10), or pST (40 microg/kg BW i.m.; n = 10) from d 1 to 5 after weaning (d 0). Ovaries were collected, the diameter of each follicle > or = 2 mm was measured, and fluid from the 20 largest follicles was assessed for IGF-I, IGF binding proteins (IGFBP), estradiol, progesterone, and testosterone. The total number (27.7, 25.3, and 29.1 for saline, insulin, and pST, respectively; SEM = 3.2) and average diameter (4.7, 5.2, and 5.5 mm for saline, insulin, and pST treatments, respectively; SEM = .3 mm) of ovarian follicles were not affected by insulin or pST treatment. The pST and insulin increased follicular fluid estradiol and testosterone in medium and large follicles compared to fluid from saline-treated sows, but the increase was greater for insulin than for pST treatment (treatment x size interaction, P < .01). Similarly, progesterone concentrations in follicular fluid were higher in medium and large follicles after insulin treatment, and pST treatment induced higher progesterone concentrations in small follicles and increasingly lower concentrations of progesterone in medium and large follicles (treatment x size interaction, P < .0007) compared to saline treatment. Follicular fluid IGF-I was greater (treatment x health interaction, P < .0001) in atretic and nonatretic follicles from pST-treated sows than in those from insulin- and saline-treated sows. Follicular fluid IGFBP-2 (tendency, P < .07) and IGFBP, possibly representing IGFBP-5 (30 kDa) and IGFBP-4 (22 kDa), were higher in atretic follicles than in nonatretic follicles (P < .05), whereas IGFBP-3 was not influenced by health status. The 30- and 22-kDa IGFBP were also influenced by treatment, increasing due to pST compared with saline or insulin treatments (P < .008). Follicular fluid IGFBP-2 and IGFBP-3 were not influenced by treatment. In conclusion, pST and insulin positively influenced follicular steroidogenesis and possibly follicular development, although through different mechanisms.
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PMID:Comparative effects of insulin and porcine somatotropin on postweaning follicular development in primiparous sows. 962 54

Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.
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PMID:Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease. 962 36

Many men with idiopathic osteoporosis have reduced circulating insulin-like growth factor-I (IGF-I) levels. The major source of circulating IGF-I is GH-mediated production by the liver. The known anabolic effects of GH on the skeleton raised the possibility of GH deficiency in these men. We sought to test this hypothesis in this study. Fourteen men (mean age, 52.1 +/- 3.2 yr, range 31-68) with idiopathic osteoporosis were studied. Mean lumbar spine bone mineral density (BMD) was 0.723 g/cm2, T score -3.5; femoral neck BMD was 0.642 g/cm2, T score, -3.07; distal (1/3) radius BMD was 0.708 g/cm2, T score, -2.05. Eleven of 14 (79%) had frank reductions in serum IGF-I levels compared with age and sex-matched values (158.5 +/- 50 SD vs. 180 +/- 45 SD). GH secretion was stimulated by iv arginine infusion (30 g) over 30 min followed 1 h later by oral L-dopa (500 mg). Serum GH was measured at time (t) = -15, 0, 30, 45, 60, 90, 120, 150, and 180 min. All patients responded to at least one stimulus with the majority (n = 9) responding to both. Five patients responded either to arginine or to L-dopa but not to both. Baseline GH for the entire group was 0.77 + 0.08 ng/mL (SEM). Peak GH following arginine (t = 45-60 min) was 14.0 +/- 2.8 ng/mL, a 17.7 +/- 2.8-fold rise. Peak GH following L-dopa (t = 120-180 min) was 5.7 +/- 1.0 ng/mL, a 9.2 +/- 2.2-fold rise. No difference in maximal secretion was observed between those with low or normal IGF-I levels. Neither IGF-I nor IGF binding protein-3 concentrations changed significantly during the short period of GH stimulation. These data suggest that men with osteoporosis and reduced IGF-I levels do not appear to have a deficiency in the GH axis. Other hormonal or local factors may be important in regulating IGF-I expression. Deficiencies of IGF-I production at skeletal sites may be important in the pathogenesis of this syndrome.
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PMID:Normal growth hormone secretory reserve in men with idiopathic osteoporosis and reduced circulating levels of insulin-like growth factor-I. 966 47

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