Blood levels of insulin-like growth factors I and II in neonates of non-insulin-dependent diabetic rats

Circulating levels of insulin like growth factor I (IGF-I) and insulin like growth factor II (IGF-II) were evaluated in plasma samples during the first 72 h of life in neonates of diabetic and control mother rats. Diabetes had been induced in the diabetic dams by streptozotocin at 2 days of age. The rats developed non-insulin dependent diabetes (at 6 weeks of age) and became pregnant at 11 weeks of age. Maternal blood glucose levels were higher in the diabetic mothers (P<0.05) during the last two-thirds of gestation. Complications occurred at the end of 7.1% of the diabetic pregnancies but none of the controls. Analysis of neonates plasma glucose, IGF-I, and IGF-II concentrations in the first 12, 24, 48, and 72 h after birth revealed higher glucose levels in neonates of diabetic mothers at 72 h compared with controls (118±7 vs 85±5 mg/dl,P<0.05) but there was no difference in IGF-I or IGF-II levels between the groups at any time point. Thus, acquired impaired glucose homeostasis may be seen in neonates of mildly diabetic mothers at early stages of their life but their circulating insulin-like growth factors levels are normal. These data do not support the proposition that fetal IGF-I and —II affect the outcome of pregnancies complicated by mild diabetes in the rodent.     

Effect of recombinant human growth hormone treatment on insulin-like growth factor (IGF-I) levels in insulin-dependent diabetic patients

Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (9 patients with preserved beta-cell activity) groups, and according to age into three groups (A=21–30 years; B=31–40 years; C=41–50 years). All control subjects belonged to group B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with rhGH treatment was variable and insignificant in comparison with basal value without age-related differences in CpN diabetics. Progressively larger age-related increases in IGF-I concentrations were observed in CpP diabetic patients. This study indicates impairment of hepatic IGF-I generation capacity in diabetic patients without residual beta-cell activity and the importance of simultaneous actions of portal insulin and GH on hepatic IGF-I production.     

Chronic administration of growth hormone (GH) to adult chickens exerts marked effects on circulating concentrations of insulin-like growth factor-I (IGF-I), IGF binding proteins, hepatic GH regulated gene I, and hepatic GH receptor mRNA

In young birds, growth hormone (GH) administration has been found to have only a small or even no effect on circulating concentrations of insulin-like growth factor-I (IGF-I). This is in obvious contrast to the situation in mammals. The present study examines the effect of continuous administration of GH in adult male chickens. Plasma concentrations of IGF-I were markedly elevated (2.5–3.0-fold,p<0.001) in GH-treated chickens. There were also some transient increases in the circulating levels of IGF binding proteins. Adult chickens showed other manifestations of increased responsiveness to GH, including elevated hepatic expression of GH-regulated gene-I (mRNA) with GH treatment (p<0.05), and a tendency (p<0.08) for decreased GH-receptor mRNA. In contrast to the changes in circulating concentrations of GH and IGF-I with GH treatment, no changes in plasma concentrations of thyroid hormones, reproductive hormones, glucose, or nonesterified fatty acids were evident.     

Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBP) and insulin-like growth factor type I receptor in children with various status of chronic renal failure

Chronic renal failure in childhood causes severe growth retardation. The aim of the study was to identify whether changes in the IGF system could account for the growth retardation observed in children with chronic renal failure. Insulin-like growth factor (IGF-I) serum concentrations, insulin-like growth factor binding proteins (IGFBP) and/or IGF-I binding to erythrocyte type I receptor of IGF were analysed in 69 children (mean age 11.6 +/- 4.3 years) with chronic renal failure and growth retardation (mean height -2.6 +/- 1.8 SD). The study population was separated into three groups, according to their renal status, children on conservative treatment (CRF group: n = 30), on haemodialysis (ESRD group: n = 26) and those transplanted (RT group: n = 13). Nineteen of these children, some from each of the three groups, received recombinant growth hormone therapy (rhGH). Mean basal IGF-I serum concentrations were -0.7 +/- 1.2 SD in the CRF group, + 2.1 +/- 3 SD in the ESRD group and + 1.1 +/- 2 SD in the RT group. Under rhGH therapy, as height velocity improved, mean IGF-I concentrations increased up to + 3.1 +/- 0.6 SD in the CRF group, to + 6.9 +/- 2.8 SD in the ESRD group and to + 3.9 +/- 2 SD in the RT group. Basal IGFBP-3 levels, studied by Western Ligand Blot were low in the CRF group and high in the ESRD and normal in the RT groups, whereas IGFBP-2 and a 30-32 kDa IGFBP were always high in all cases. Western immunoblot analysis showed that this 30-32 kDa IGFBP was mostly composed of IGFBP-1 and IGFBP-6 in all three groups, but IGFBP-6 was particularly abundant in the ESRD group. IGFBP-6 concentrations assessed by RIA were moderately increased in CRF children (392 +/- 177 ng/mL) and very high in children on ESRD (2094 +/- 1525 ng/mL) when compared to normal values (131 +/- 42 ng/mL). Binding studies of IGF type I receptor showed that there was no particular difference in IGF-I binding between renal failure patients and normal children. In poorly growing children, especially in ESRD children and to a lesser extent in RT children, high concentrations of IGF-I and IGFBP-1, 2, 3 and 6, suggest a resistance mainly by a sequestration mechanism. Moreover, in the CRF group, especially in the younger children, low levels of IGF-I and IGFBP-3 are evocative of an associated resistance at the GH receptor level.     

Direct effect of insulin and insulin-like growth factor-I on the secretory activity of rat pancreatic beta cells

Summary Purified pancreatic Beta cells were labelled with ³H-tyrosine before studying their secretory activity in perifusion. At 1.4 mmol/l glucose, the cells released similar fractions (0.01% per min) of their contents in preformed and in newly formed insulin. At 20 mmol/l glucose plus 10^–8 mol/l glucagon, these fractional release rates increased by 16 and 40-fold respectively. The preferential release of newly synthesized as compared to stored insulin is attributable to a heterogeneity in individual cell responses. The secretory responsiveness to glucose plus glucagon was completely suppressed by 10^–7 mol/l clonidine. Insulin induced a 20% reduction at 10^–6 mol/l, but remained without effect at 10^–7 mol/l. Insulin-like growth factor-I provoked a 30% decrease at 5.10^–9 mol/l. It is concluded that the type-I insulin-like growth factor receptors on pancreatic Beta cells mediate a suppressive action on the insulin release process. Their high affinity for insulin-like growth factor-I allows physiologic levels of this peptide to participate in the regulation of insulin release. Their low affinity for insulin provides the basis for a minor feedback action by this hormone at concentrations exceeding the normal circulating levels.Part of this study has been presented at the 25th Annual Meeting of the European Association for the Study of Diabetes, Lisbon, Portugal, 1989     

原发性高血压赖诺普利治疗前后血清胰岛素样生长因子-I的变化

目的观察原发性高血压(EH)患者服用赖诺普利治疗前后血清胰岛素样生长因子-I(IGF-I)的变化,探讨IGF-I在EH的发生发展过程中所起的可能作用。方法47例EH患者均行超声心动图检查,用放免法测定赖诺普利治疗前、治疗后半年及23例正常对照者血清IGF-I水平。结果EH患者血清IGF-I水平明显高于对照组分别为(22.23±10.06)ng/ml对(15.91±7.59)ng/ml,P<0.01。I~Ⅲ级间比较也有显著性差异(F=3.53,P<0.05),Ⅲ级(28.61±13.10)ng/ml高于Ⅱ级(22.64±9.94)ng/ml,Ⅱ级高于I级(18.09±6.11)ng/ml。EH伴左心室肥厚(LVH)者高于无LVH者(25.95±11.20)ng/ml对(18.68±7.43)ng/ml,P<0.05。IGF-I与左心室重量指数中度相关(r=0.54)。赖诺普利治疗6个月后,血清IGF-I水平由(22.23±10.06)ng/ml降至(16.82±7.93)ng/ml,P<0.05。结论EHLVH患者IGF-I水平升高,赖诺普利治疗后IGF-I水平下降,IGF-I可能参与EHLVH的形成。     

Elevated levels of insulin-like growth factor (IGF) binding protein-3 in rheumatoid arthritis synovial fluid inhibit stimulation by IGF-I of articular chondrocyte proteoglycan synthesis

The objective of this study was to quantify insulin-like growth factor (IGF) binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with rheumatic diseases and to study the role of these proteins in the regulation of cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2, IGFBP-3, IGF-I, IGF-II, interleukin-1β (IL-1β) and tumour necrosis fac-tor α (TNFα) was undertaken in the SF and plasma of 115 patients with rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other rheumatic disorders. We also determined the effects of SF on bovine cartilage PG synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and 28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA compared to age- and sex-matched OA controls (determined by RIA and confirmed by Western ligand blot). IGF-I and IGF-II did not differ significantly between the two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG synthesis in culture, and more than 60% of this activity was neutralised by a specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA patients, the SF concentration of IGFBP-3 was positively correlated with SF levels of IL-1β and TNFα, with the serum level of C-reactive protein and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under the conditions studied, the most important anabolic factor in human SF with respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes, thus interfering with cartilage PG synthesis in RA. Received: 30 November 1996 / Accepted: 19 February 1997     

The circulating molecular weight forms of infused recombinant insulin-like growth factor-I and effects on glucose and fat metabolism in lambs

Summary We have investigated the relationship between the plasma distribution of infused recominant insulin-like growth factor-I across the insulin-like growth factor binding proteins and the resultant effects on glucose and fat metabolism. The studies were performed in 24-h fasted ram lambs which received primed constant infusions of ³H labelled glucose tracer. When isotopic equilibrium had been reached, the animals received 90-min infusions of human insulin-like growth factor-I at various doses (2.5, 20, 40 and 120 g· kg^–1·h^–1, n=3 for each dose). Total plasma insulin-like growth factor-I was significantly elevated by infusion at a rate of 40 g·kg^–1·h^–1 (from 185±14 g/l to 442±41 g/l, p<0.05) and 120g·kg^–1h^–1 (from 181±2 g/l to 953±39 g/1, p<0.005). The plasma concentrations of insulin-like growth factor-I not associated with binding proteins remained undetectable (<15 g/l) at the end of the 2.5 and 20 g·kg^–1·h^–1 doses, but were significantly elevated at the end of the 40 and 120 g·kg^–1·h^–1 infusions (to 71±14 g/l, p<0.05 and 176±55 g/l, p<0.01 respectively). The infused insulin-like growth factor-I associated primarily with 35–60 kilodalton binding proteins. Glucose kinetics were significantly altered only by the highest dose infusion, during which there was a fall in plasma glucose concentration from 3.5±0.2 mmol/l to 1.9±0.2 mmol/l (p<0.05). This was due to a 51% increase in the rate of glucose clearance. There was no significant change in the rate of glucose production. The plasma concentrations of glycerol and non-esterified fatty acid were not changed by any of the doses infused. We conclude that the hypoglycaemic action of infused recombinant insulin-like growth factor-I relates to a marked elevation of free insulin-like growth factor-I in the plasma, but that a threshold concentration of free insulin-like growth factor-I must be exceeded before this action is observed. The hypoglycaemic action of recominant insulin-like growth factor-I results primarily from an increase in glucose clearance while glucose metabolism was more sensitive than fat metabolism to infused recominant insulin-like growth factor-I. Both these actions contrast with those of insulin, and suggest that the acute metabolic effects of recombinant insulin-like growth factor-I are not mediated simply by cross-reaction with insulin receptors.     

Improvement of lipid profile in Type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I

Summary Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2×120 g insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean ± SD) 3.1±2.6, 1.3±1.0, 6.3±1.3, and 4.5±1.1 mmol/l and decreased to 1.6±0.8, 0.6±0.4, 5.0±1.0, and 3.5±1.1 mmol/l, respectively, on the last treatment day (p<0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48±22 and 32±18% of control (p<0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.     

Divergence of mucosal and motor effects of insulin-like growth factor (IGF)-I and LR3IGF-I on rat isolated ileum following abdominal irradiation

BACKGROUND AND AIMS: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF-I (5 mg/kg per day) and the more potent analog LR3IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation. METHODS: Intestinal motor activity was recorded from 6-8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini-pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR3IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitude long-duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non-irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system. RESULTS: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR3IGF-I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF-I and LR3IGF-I compared with vehicle-treated animals. CONCLUSIONS: In radiation enteritis, IGF-I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis.     

Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels

BACKGROUND: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I. MATERIALS AND METHODS: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden (CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort (NSHDC) study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3' region of the IGF-I gene in relation to circulating IGF-I levels. RESULTS: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC (P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I (P = 0.001 and P < 0.0001, respectively). CONCLUSIONS: Genetic variation in the 3' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.     

非霍奇金淋巴瘤患者血清胰岛素样生长因子-1及其结合蛋白-3表达水平的初步观察

目的:探讨非霍奇金淋巴瘤(NHL)患者血清胰岛素样生长因子-1(IGF-1)及其结合蛋白-3(IGFBP-3)表达水平及其临床意义.方法:选择28例诊断初发NHL患者(淋巴瘤组)及28例健康志愿者(对照组),化学发光法测定血清IGF-1及IGFBP-3水平并计算IGF- 1/IGFBP-3值,分析组间的差异.结果:血清IGF-1及IGFBP-3水平淋巴瘤组显著低于正常对照组(均P＜0.01);IGF-1/IGFBP-3淋巴瘤组与正常对照组差异无统计学意义(P＞0.05);不同亚型的淋巴瘤组的血清IGF-1、IGFBP-3水平及IGF-1/IGFBP-3比值的差异均未达到统计学意义(P＞0.05).结论:N HL患者血清IGF-I及IGFBP-3水平明显降低,可能与NHL相关.IGF-1/IGFBP-3比值与NHL无明显相关性,IGF-1及IGFBP-3水平与NHL的分型无明显相关.     

Insulin sensitivity and secretion in normal children related to size at birth,postnatal growth,and plasma insulin-like growth factor-I levels

Aims/hypothesis Type 2 diabetes risk is associated with low birth weight, rapid weight gain during childhood, and shorter stature and lower circulating IGF-I levels in adults. The largest variations in growth rates occur during the first postnatal years. We hypothesised that early postnatal variations in height and weight gain and IGF-I levels may be associated with risk markers for adult disease.Methods We measured the fasting insulin sensitivity (Homeostasis model) and insulin secretion post-oral glucose (insulinogenic index 0–30 min) in 851 normal 8-year-old children from a prospective birth cohort. We examined associations between size at birth, postnatal weight gain and circulating IGF-I levels with insulin sensitivity and secretion at 8 years of age.Results Fasting insulin sensitivity at 8 years was closely related to current BMI (r=–0.33, p<0.0005). Lower insulin sensitivity and higher BMI and waist circumference were all predicted by greater weight gain between birth to 3 years of age (all p<0.0005); lower birth weight was associated with reduced insulin sensitivity only in the highest current BMI tertile (r=0.17, p=0.006). In contrast, lower insulin secretion was related to smaller size at birth (p=0.01), independent of postnatal weight gain and insulin sensitivity. Lower insulin secretion was also independently related to shorter stature at 8 years of age relative to parental height (p=0.047) and with lower plasma IGF-I levels at 5 years of age (n=252, p=0.004).Conclusions/interpretation Associations between lower birth weight and insulin resistance may be dependent on rapid weight gain during the early postnatal years. However, irrespective of postnatal weight gain, smaller size at birth, lower IGF-I levels and lower childhood height predicted reduced compensatory insulin secretion.Abbreviations ALSPAC Avon Longitudinal Study of Pregnancy and Childhood     

Discordant regulation of hepatic IGF-I mRNA and circulating IGF-I during compensatory growth in a teleost, the hybrid striped bass (Morone chrysopsxMorone saxatilis)

Compensatory growth (CG) is a period of growth that exceeds normal rates after animals are alleviated of certain growth-stunting conditions. Little is known, however, about the endocrine control of CG in teleosts. So, our aim was to induce CG in juvenile hybrid striped bass (HSB, Morone chrysopsxMorone saxatilis) through manipulations in feeding regimen, and then determine whether changes in circulating insulin-like growth factor-I (IGF-I) and hepatic IGF-I gene expression accompany the CG response. A considerable catabolic state was induced in HSB fed a total of two times over 4 weeks (once each in the 2nd and 3rd week). Negative energy balance was evidenced through weight loss (-3.4% BW) and a significant drop in hepatosomatic index (HSI) from a value of 3.71 to 1.46. Upon realimentation, in which HSB were fed ad libitum 2x/day, a significant CG response was observed over a 4-week period. The CG response was characterized by an elevated specific growth rate, hyperphagia, restoration of the HSI and an improvement in feed conversion, all relative to controls that were fed ad libitum 2x/day throughout the experiment. Moreover, the CG response and catabolic state preceding it were marked by a discordant regulation in the expression of hepatic IGF-I mRNA and plasma IGF-I levels, the latter parameter paralleling changes in growth (r(2)=0.56, P<001). The catabolic state was accompanied by an 82% increase in hepatic IGF-I mRNA while levels of plasma IGF-I were significantly depressed relative to controls. During the subsequent CG response, however, hepatic IGF-I mRNA decreased by 61% while plasma IGF-I increased by 86%. The underlying mechanisms for this inverse regulation of hepatic IGF-I mRNA and circulating IGF-I are uncertain, but may reflect alterations in hepatic IGF-I mRNA production, stability, and translation such that hepatic IGF-I mRNA is accumulated during periods of catabolism and then rapidly translated and released into circulation when conditions improve. These results suggest that CG can be induced in HSB following a sufficient catabolic state and that systemic IGF-I may be an important mediator of the accelerated growth rate characteristic of CG.     

Changes in mRNA expression of grouper (Epinephelus coioides) growth hormone and insulin-like growth factor I in response to nutritional status

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are key links to nutritional condition and growth regulation in teleost. To understand the endocrine mechanism of growth regulation in grouper, we cloned the cDNAs for grouper GH and IGF-I and examined their mRNA expression during different nutritional status. Grouper GH cDNA is 936 base pairs (bp) long excluding the poly-A tail. It contained untranslated regions of 85 and 231bp in the 5'- and 3'-ends, respectively. It has an open reading frame of 612bp coding for a signal peptide of 17 amino acids (aa) and a mature hormone of 187aa residues. Based on the aa sequence of the mature hormone, grouper GH shows higher sequence identity (>76%) to GHs of perciforms than to GHs of cyprinids and salmonids (53-69%). Grouper preproIGF-I cDNA consisted of 558bp, which codes for 186aa. This is composed of 44aa for the signal peptide, 68aa for the mature peptide comprising B, C, A, and D domains, and 74aa for the E domain. Mature grouper IGF-I shows very high sequence identity to IGF-I of teleost fishes (84-97%) compared to advanced groups of vertebrates such as chicken, pig, and human (80%). Using DNA primers specific for grouper GH and IGF-I, the changes in mRNA levels of pituitary GH and hepatic IGF-I in response to starvation and refeeding were examined by a semi-quantitative RT-PCR. Significant elevation of GH mRNA level was observed after 2 weeks of food deprivation, and increased further after 3 and 4 weeks of starvation. GH mRNA level in fed-controls did not change significantly during the same period. Hepatic IGF-I mRNA level decreased significantly starting after 1 week of starvation until the 4th week. There was no significant change in IGF-I mRNA levels in fed-controls. One week of refeeding can restore the GH and IGF-I mRNA back to its normal levels. Deprivation of food for 1-4 weeks also resulted in cessation of growth and decrease in condition factor.     

Insulin-like growth factor I levels during growth hormone (GH) replacement in GH-deficient adults: a gender difference

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 ± 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p < 0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p < 0.01). IGF-1 concentrations were higher in men than women (p < 0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p < 0.01). At the end of the study the mean GH dose was lower in men than in women (p < 0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.     

Effects of aging and sex on plasma insulin-like growth factor I (IGF-I) levels in normal adults

Effects of aging and sex on total plasma IGF-I levels were studied in 207 normal adults (103 males and 104 females), aged 21 to 80 years. Plasma IGF-I concentrations were measured by specific radioimmunoassay after extraction with acid-ethanol. Plasma IGF-I levels ranged from 50.8 to 480.6 micrograms/l with a mean (+/- SD) value of 200.7 +/- 81.9 micrograms/l in these normal adults. The mean plasma IGF-I levels were higher in females than in males in the second decade (332.6 +/- 63.9 vs 252.4 +/- 45.2 micrograms/l, p less than 0.01), whereas there was no sex difference in plasma IGF-I levels in elderly subjects. In both sexes, plasma IGF-I levels declined with age. In females, the slope of the regression line was much steeper in the young group (aged 21 to 40 years) than in the middle-aged and elderly group (aged 41 to 80 years) (y = -11.3x + 641.7, r = -0.538, p less than 0.005 and y = -1.97x + 289.3, r = -0.308, p less than 0.01). In males, plasma IGF-I linearly declined with age and the slope of the regression line (y = -2.36x + 322.2, r = -0.480, p less than 0.005) was not considerably different from that of the middle-aged and elderly group in females.     

Androgen effects on plasma GH, IGF-I, and 41-kDa IGFBP in coho salmon (Oncorhynchus kisutch)

Among many species of salmonids, fast growing fish mature earlier than slow growing fish, and maturing males grow faster than non-maturing ones. To study the potential endocrine basis for this reciprocal relationship we examined the in vivo effects of the androgens, testosterone (T) and 11-ketotestosterone (11-KT), on plasma growth hormone (GH), insulin-like growth factor-I (IGF-I) and 41-kDa IGF binding protein (41-kDa IGFBP) (putative IGFBP-3) in coho salmon, Oncorhynchus kisutch. Immature male and female, two-year old fish (avg. wt. 31.7 +/- 0.63 g) were injected with coconut oil containing T or 11-KT at a dose of 0.1, 0.25, or 1 microg/g body weight. Blood samples were taken 1 and 2 weeks postinjection, and analyzed by immunoassay for T, 11-KT, GH, IGF-I, and 41-kDa IGFBP. Steroid treatments elevated the plasma T and 11-KT levels to physiological ranges typical of maturing fish. Plasma IGF-I and 41-kDa IGFBP levels increased in response to both T and 11-KT in a significant and dose-dependent manner after 1 and 2 weeks, but GH levels were not altered. These data suggest that during reproductive maturation, in addition to the previously demonstrated effects of the IGFs on steroidogenesis, the gonadal steroids may in turn play a significant role in regulating IGF-I and its binding proteins in fish. The interaction between the reproductive and growth axes may provide a regulatory mechanism for bringing about the dimorphic growth patterns observed between maturing and non-maturing salmonids and other species of fish.