Decrease In Insulin-like Growth Factor Research Articles

Alcohol Suppresses Insulin‐Like Growth Factor‐1 Gene Expression in Prepubertal Transgenic Female Mice Overexpressing the Bovine Growth Hormone Gene

Background Alcohol (ALC) delays puberty in female rats and alters the development of a normal menstrual pattern in rhesus monkeys. These actions are associated with depressed serum levels of growth hormone (GH), luteinizing hormone and insulin‐like growth factor‐1 (IGF‐1). The mechanism of this ALC‐induced depression in IGF‐1 is not known, however, could be due to depressed GH and, possibly, to an alteration in the hepatic GH receptor. To assess whether ALC has a direct action at the liver, we used a transgenic mouse model that overexpresses GH, allowing assessment of potential direct actions of ALC on the level of either the GH receptor or the IGF‐1–synthesizing machinery within the hepatocyte.Methods One group of transgenic mice was fed a liquid diet containing ALC. The second group was pair‐fed the companion isocaloric control liquid diet. The third group of transgenic mice was fed Lab Chow and water. The fourth group consisted of normal (nontransgenic) littermates fed Lab Chow and water. Animals received their respective diets for 5 days. Mice were killed during their late juvenile stage of development, and tissues and blood collected and frozen.Results The ALC‐fed transgenic mice showed a decrease (p < 0.01) in hepatic IGF‐1a and IGF‐1b messenger RNA levels compared with transgenic controls, and this paralleled a decrease (p < 0.01) in serum IGF‐1. ALC did not alter the circulating levels of bovine GH held constant by the promotor and did not alter mouse GH receptor protein levels as analyzed by Western blotting.Conclusions Using this transgenic animal model that maintains circulating GH in the presence of ALC, we found that the ability of ALC to suppress prepubertal Igf1 gene expression can also occur independently of any alterations in the level of circulating GH. This direct effect on the hepatocyte is a postreceptor event because the GH receptor protein levels were not altered by ALC exposure.

Effect of feed restriction on plasma concentration of hormones and metabolites in steers fed grass silage

Plasma concentrations of hormones and metabolites were measured in growing steers to establish their relation with degree of feed restriction. Sixty medium frame beef steers (259 ± 29 kg) were divided in groups of five and fed during 3 mo either timothy (T) or bromegrass (B) harvested at stem elongation of the first cut or at boot stage of the aftermath. Forages were fed at one of three levels of intake: ad libitum (FF), 80% of FF, or 65% of FF. Plasma concentrations of growth hormone (GH), insulin, glucagon, insulin-like growth factor-1 (IGF-1), glucose and nonesterfied fatty acids (NEFA) were measured on day 1 and day 78 before the morning meal. The effect of a meal on GH, insulin, glucagon, IGF-1, glucose and NEFA concentrations was also determined in 24 steers sampled from 3 h before to 3 h after a meal. Severity of feed restriction resulted in a linear decrease (P < 0.05) of plasma glucagon (0.139, 0.130, 0.121 ± 0.005 ng mL–1) and IGF-1 (109, 98, 84 ± 7 ng mL–1). Insulin concentration tended to be affected quadratically (0.37, 0.35, 0.27 ± 0.04ng mL–1 for FF, 80% of FF and 65% of FF, respectively, P < 0.10). Ingestion of a meal resulted in a decrease (P < 0.05) of GH, NEFA and glucose, and an increase of insulin concentrations (P < 0.05). There was a positive correlation (r = 0.53, P < 0.05) between IGF-1 and average daily gain, and lipid percentage of carcasses suggesting that IGF-1 is related to growth rate and fat accumulation in growing steers. Key words: Feed restriction, growth hormone, insulin, IGF-I, metabolites, grass silage

In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist.

Neutralization of IL-6 represents an attractive therapeutic option in several diseases, including B cell neoplasia, osteoporosis, and autoimmunity. Therapeutic attempts in humans have shown that administration of injectable doses of a mAb to IL-6 does not provide efficient neutralization of the cytokine in vivo. Therefore, alternative approaches are needed. In this study, we evaluated whether the Ab response to human IL-6 (hIL-6) elicited by vaccination with Sant1 (a hIL-6 variant with seven amino acid substitutions) was able to fully correct in vivo the clinical and biological effects of a chronic endogenous overproduction of hIL-6 in the hIL-6-transgenic NSE/hIL-6 mice. Because of the overexpression of hIL-6, occurring since birth, with circulating levels in the nanogram per milliliter range, NSE/hIL-6 mice have a marked decrease in growth rate, associated with decrease in insulin-like growth factor I levels, and represent an animal model of the growth impairment associated with human chronic inflammatory diseases. Following immunization with Sant1, but not with hIL-6, NSE/hIL-6 mice developed high titers of polyclonal Abs to hIL-6. The Abs, acquired by transplacental transfer, effectively neutralized IL-6 activities in vivo as shown by the complete correction of the growth defect and normalization of insulin-like growth factor levels in the hIL-6-transgenic offspring. Immunization with Sant1 could therefore represent a novel and simple therapeutic approach for the specific neutralization of IL-6 in humans.

Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis

BACKGROUNDLinear growth retardation is a frequent complication of inflammatory bowel disease in children. The precise mechanisms causing growth failure are not known.AIMSTo determine the relative contribution of reduced calorie intake...

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Growth Hormone Treatment Prevents the Decrease in Insulin-Like Growth Factor I Gene Expression in Patients Undergoing Abdominal Surgery

Growth Hormone Treatment Prevents the Decrease in Insulin-Like Growth Factor I Gene Expression in Patients Undergoing Abdominal Surgery

Growth hormone treatment prevents the decrease in insulin-like growth factor I gene expression in patients undergoing abdominal surgery.

Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg.day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg.day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/- 265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3 (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.

Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy.

Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer patients undergoing six courses of adjuvant chemotherapy. The only observed variation was a slight decrease (10%) in IGF-1 concentrations, assayed before treatment, between the first and the second courses of chemotherapy. During chemotherapy courses, there were no statistically significant variations in IGF-1. These results suggest that chemotherapy, unlike the specific hormonal treatments tamoxifen and somatostatin, certainly does not act via a decrease in plasma IGF-1.

Beta-adrenergic receptors mediate a stress-induced decrease in IGF-II mRNA in the rat cerebellum.

1. Exposure to a combined forced swimming-confinement stress resulted in a decrease in insulin-like growth factor II (IGF-II) mRNA levels in the whole brain (without the cerebellum) and in the isolated brain areas of the cerebral cortex, the hippocampus, and the cerebellum. 2. In an effort to elucidate the neurotransmitter systems involved in this stress-induced decrease, animals were injected prior to exposure to the stress, with either propranolol, diazepam, or MK-801. 3. Administration of diazepam or MK-801 did not affect the stress-induced decrease in IGF-II mRNA in any of the three brain areas examined. 4. Administration of propranolol prior to the exposure to the stress inhibited the stress-induced decrease in IGF-II mRNA in the cerebellum. Propranolol had no such effect in the cerebral cortex or the hippocampus. 5. Our results suggest that in the cerebellum, the stress-induced decrease in IGF-II mRNA is mediated by beta 2-adrenergic receptors.

Follicular Dominance in Cattle Is Associated With Divergent Patterns of Ovarian Gene Expression for Insulin-Like Growth Factor (IGF)-I, IGF-II, and IGF Binding Protein-2 in Dominant and Subordinate Follicles

A decrease in insulin-like growth factor (IGF) binding protein (BP) amount occurs within the follicular fluid of dominant ovarian follicles. At the same time, concentrations of follicular fluid IGF-I do not change. The mRNA for IGF-I, IGF-II, IGFBP-2, and IGFBP-3 in dominant and subordinate follicles were measured to determine if changes in IGF or IGFBP gene expression are associated with follicular dominance. Heifers were ovariectomized during a follicular wave, either during early-dominance (emerging dominant follicle, 9 mm diameter) or mid-dominance (established dominant follicle, 14–16 mm diameter). Follicles were classified as either dominant (DF), subordinate (SF), or not-recruited (NRF; small antral follicles). mRNA was localized by in situ hybridization and measured by image analyses. The IGF-I mRNA (granulosa cells) was greatest in DF and increased in DF, SF, and NRF from early- to mid-dominance. Likewise, IGF-II mRNA (theca cells) was greatest in DF compared with SF or NRF. The IGFBP-2 mRNA (granulosa cells), however, was nearly undetectable in DF, whereas adjacent SF expressed abundant IGFBP-2 mRNA. The NRF were not uniform in their IGFBP-2 expression because only 5 of 13 NRF had IGFBP-2 mRNA. The IGFBP-3 mRNA (granulosa cells) was found only in two NRF, suggesting that local synthesis is not a predominant source of follicular fluid IGFBP-3. These data show that changes in gene expression for IGFBP-2 are opposite to those for IGF-I or IGF-II. Increased IGF-I and IGF-II mRNA and decreased IGFBP-2 mRNA within the DF may be one mechanism leading to follicular dominance. The opposite pattern of IGFBP-2 gene expression in SF and some NRF may lead to follicular atresia.

Transynaptic modulation by insulin-like growth factor I of dendritic spines in Purkinje cells

Purkinje cells synthesize insulin-like growth factor I and express insulin-like growth factor I receptors during their entire life. An additional source of insulin-like growth factor I for these cells is provided by climbing fiber afferents originating in the inferior olive nucleus. Recently we found that insulin-like growth factor I from the inferior olive is necessary for motor learning processes probably involving Purkinje cell synaptic plasticity. We now studied whether inferior olive insulin-like growth factor I influences the synaptic structure of Purkinje cells, because changes in synaptic morphology are related to neuronal plasticity events. We injected an insulin-like growth factor I antisense in the inferior olive of adult rats, a procedure which we previously found to elicit a significant and reversible decrease of insulin-like growth factor I levels in the contralateral cerebellum. Ultrastructural analysis of the cerebellar cortex of these animals showed a significant reduction in the size of dendritic spines on Purkinje cells of antisense-treated rats compared to controls. The decrease in spine size was linked to a diminished numerical density of dendritic spines on Purkinje cells, without affecting the numerical density of synapses in the molecular layer of the cerebellum. This reduction was not due to a change in the thickness of the molecular layer. Climbing or parallel fiber terminals were also unaffected.Taken together with previous findings, these results support a role for insulin-like growth factor I produced in the inferior olive in the maintenance of Purkinje cell synaptic plasticity.

Interference of angiotensin-converting enzyme inhibitors on erythropoiesis in kidney transplant recipients: role of growth factors and cytokines.

Recent data indicate that factors other than erythropoietin (EPO), such as insulin-like growth factor 1 (IGF-1), can promote erythropoiesis in vitro and correct the anemia of chronic renal failure in vivo. IGF-1 is produced by the liver under growth hormone control, as well as by other sources, including the kidney. The erythropoietic role of growth factors and cytokines and their possible modulation by angiotensin-converting enzyme inhibitors (ACEI) has never been explored. This study evaluated the serum levels of EPO, IGF-1, interleukin (IL)-2, IL-3, and granulocyte macrophage-colony-stimulating factor in 40 kidney transplanted patients with or without posttransplant erythrocytosis (PTE) and in 10 living kidney donors. Then, the effect of ACEI therapy on the above pattern was examined in patients with PTE. EPO and IGF-1 serum levels were significantly higher in patients with PTE than in patients without PTE and in living kidney donor subjects. ACEI therapy significantly reduced hematocrit (Hct) as well as circulating IGF-1 and EPO levels. Of note, the decrease in IGF-1 was prominent mainly in those patients whose EPO levels were not significantly modified by ACEI therapy. In all of the patients Hct levels displayed a direct relationship with circulating IGF-1 levels, but not with EPO concentration. Growth hormone did not significantly differ among the groups examined, whereas it steeply increased under ACEI. Finally, no significant difference in IL-2, IL-3, and granulocyte macrophage-colony-stimulating factor serum levels was detected. IGF-1 seems to play a role in the ACEI-related decrease of Hct in patients with PTE, chiefly in patients without any modification of EPO serum levels.

Insulin-like growth factor-1 and cardiac mass in essential hypertension

Preliminary studies have shown that patients with essential hypertension and left ventricular hypertrophy have an excess of circulating insulin-like growth factor-1 (IGF-1). In addition, an association has been found between the decrease in IGF-1 after antihypertensive treatment and regression of left ventricular hypertrophy. To determine whether the effect of angiotensin converting enzyme (ACE) inhibitors on left ventricular hypertrophy in patients with essential hypertension is related to ACE inhibitor effects on IGF-1 levels. The relationship between echocardiographically determined left ventricular hypertrophy and plasma IGF-1 levels was investigated in 87 patients with essential hypertension before and after 6 months of randomly allocated treatment with captopril (n = 30), lisinopril (n = 37) or quinapril (n = 20). The control group consisted of 30 age- and sex-matched normotensive subjects without left ventricular hypertrophy. Baseline IGF-1 levels were higher in hypertensive patients than in normotensive controls (280 +/- 21 versus 240 +/- 15 ng/ml, means +/- SEM, P < 0.02). IGF-1 levels were higher in hypertensive patients with left ventricular hypertrophy (n = 25, 316 +/- 41 ng/ml) than in those without left ventricular hypertrophy (n = 62, 242 +/- 16 ng/ml, P < 0.05). There was a direct correlation between baseline IGF-1 and left ventricular mass in the hypertensive patients (r = 0.365, P < 0.001). All three ACE inhibitors caused similar reductions in IGF-1 levels, the left ventricular mass index and blood pressure after the treatment period. The effect of ACE inhibition on mean blood pressure was similar in patients with (-13%) and without (-12%) a regression of left ventricular hypertrophy. The mean change in IGF-1 levels with treatment was more pronounced in those patients in whom left ventricular hypertrophy regressed (-25 versus -12%). These results indicate that circulating IGF-1 levels are increased in essential hypertension. Furthermore, there is an association between high IGF-1 levels and left ventricular hypertrophy in hypertensive patients. Our findings suggest that the ability of ACE inhibitors to induce regression of hypertensive cardiac hypertrophy may be related to their ability to normalize IGF-1 and also supports the view that ACE inhibition affects left ventricular mass through pathways other than blood pressure reduction.

Androgenic progestogens oppose the decrease of insulin-like growth factor I serum level induced by conjugated oestrogens in postmenopausal women. Preliminary report

Oral oestrogen treatment in postmenopausal women causes a decrease of insulin-like growth factor I (IGF-I) serum level, probably through a hepatocellular effect. To explore the possibility that the androgenic progestogens oppose this effect, serum IGF-I and sex hormone binding globulin (SHBG) were evaluated in two groups of patients treated respectively with oral conjugated oestrogens (oCE) or transdermal oestradiol (tdE 2), in a first phase with the addition of dydrogesterone (DYDR), a non-androgenic progestogen, and subsequently with the addition of norethisterone acetate (NETA). With respect to basal values, treatment with oCE + DYDR caused an increase of SHBG ( P < 0.002) and a decrease of IGF-I serum levels ( P < 0.05); the shift to NETA addition opposed both effects: SHBG levels decreased partially but significantly ( P < 0.01 vs. oCE + DYDR) and IGF-I returned to basal values with a significant increase with respect to the oCE + DYDR phase ( P < 0.02). No changes were observed in the tdE 2 + DYDR treated women; in this group the shift to NETA addition caused a significant decrease of SHBG values ( P < 0.001 vs. before treatment and vs. tdE 2 + DYDR phase) and a slight increase of IGF-I values. These differential effects on IGF-I and SHBG serum levels might be relevant as far as breast cancer risk is concerned.

Hormonal changes in elderly men with non-insulin-dependent diabetes mellitus and the hormonal relationships to abdominal adiposity.

To elucidate the hormonal changes in elderly men with non-insulin-dependent diabetes mellitus (NIDDM) and the hormonal relationship to abdominal adiposity, we measured serum insulin-like growth factor 1 (IGF-1), T3, T4, TSH, testosterone, LH, and FSH levels, body mass index (BMI), skinfold thickness and waist-to-hip circumference ratio (W/H) in 40 elderly men (aged over 60 years), 20 elderly men with NIDDM (aged over 60 years) and 30 men aged 21-40 years (controls). The results showed that elderly men with and without NIDDM had lower serum T3, testosterone and IGF-1 levels and higher serum LH and FSH levels compared with controls. Elderly men with NIDDM had even lower serum testosterone levels compared with elderly men without NIDDM. Elderly men had a higher W/H ratio compared with controls. Elderly men with NIDDM had a higher W/H ratio, BMI and skinfold thickness than elderly men without NIDDM. Age was positively correlated with the W/H ratio. Serum LH and FSH levels were positively correlated with the W/H ratio, and serum IGF-1, T3 and testosterone levels were negatively correlated with W/H ratio. Age, serum IGF-1, T3, T4, TSH, LH and FSH levels were not related to BMI or skinfold thickness. Only serum testosterone levels were negatively correlated with BMI or skinfold thickness. In conclusion, elderly men with NIDDM were associated with a marked decrease in serum testosterone levels and an increase of the W/H ratio compared to other groups in addition to the age-associated decrease of serum T3, IGF-1 and testosterone levels and increase of the W/H ratio and serum LH and FSH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of aging and dietary restriction on tissue protein synthesis: relationship to plasma insulin-like growth factor-1.

Insulin-like growth factor-1 (IGF-1) decreases with age in many species and appears to have an important role in the age-related decline in capacity for protein synthesis with age. The goals of these studies were to determine whether (a) ad libitum fed mice demonstrate age-related decreases in IGF-1, (b) the relationship between IGF-1 and age-related changes in protein synthetic capacity in ad libitum fed animals, and (c) whether moderate dietary restriction (which increases both life span and protein synthetic capacity) delays age-related changes in protein synthesis and plasma IGF-1. These studies indicate that (a) in ad libitum fed animals, plasma IGF-1 decreases with age between 10 and 15 months and moderate dietary restriction decreases plasma IGF-1 in young but not older animals, and (b) the temporal changes in protein synthesis are tissue specific; moderate dietary restriction either increases or prevents the age-related decline in tissue protein synthesis. Results suggest that in normal aging, decreases in IGF-1 are associated with the decline in protein synthesis but that other regulatory mechanisms appear to have an important role in this process. Dietary restriction decreases plasma IGF-1 in young animals and either increases protein synthesis or prevents the age-related decline in protein synthesis, suggesting that the effects of dietary restriction are not mediated via increases in plasma IGF-1.

Identification of determinants that confer ligand specificity on the insulin receptor.

We have previously shown, using truncated soluble recombinant receptors, that substituting the 62 N-terminal amino acids of the alpha subunit from the insulin-like growth factor I receptor (IGFIR) with the corresponding 68 amino acids from the insulin receptor (IR) results in a chimeric receptor with an approximately 200-fold increase in affinity for insulin and only a 5-fold decrease in insulin-like growth factor I (IGFI) affinity (Kjeldsen, T., Andersen, A. S., Wiberg, F. C., Rasmussen, J. S., Schäffer, L., Balschmidt, P., Møller, K. B., and Møller, N. P. H. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4404-4408). We demonstrate that these 68 N-terminal amino acids of the IR also confer insulin affinity on the intact IGFI holoreceptor both in the membrane-bound state and when solubilized by Triton X-100. Furthermore, this domain can be subdivided into two regions (amino acids 1-27 and 28-68 of the IR alpha subunit) that, when replacing the corresponding IGFIR sequences, increases the insulin affinity of truncated soluble receptor chimeras 8- and 20-fold, respectively, with only minor effects on the IGFI affinity. Within the latter of these two regions, we found that amino acids 38-68 of the IR, representing 13 amino acid differences from IGFIR, confer the same 20-fold increase in insulin affinity on the IGFIR. Finally, the amino acids from position 42 to 50 are not responsible for this increase in insulin affinity. We thus propose that at least two determinants within the 68 N-terminal amino acids of the insulin receptor are involved in defining the ligand specificity of the insulin receptor, and that one or a combination of the remaining seven amino acid differences between position 38 and 68 are involved in conferring insulin affinity on the insulin receptor.

Influence of Age and Long-term Dietary Restriction on Plasma Insulin-like Growth Factor-1 (IGF-1), IGF-1 Gene Expression, and IGF-1 Binding Proteins

The purpose of these studies was to determine more accurately the relationship between IGF-1 and life span, and to determine whether moderate dietary caloric restriction alters the age-related changes in IGF-1. Studies included an assessment of plasma IGF-1, hepatic IGF-1 mRNA, and plasma IGF-1 binding proteins (IGF-1-BP). Rats (6, 12, 22, and 28 months of age) were fed ad libitum or maintained on a diet 60% of ad libitum. In ad libitum fed animals, plasma IGF-1 decreased by 20% between 6 and 28 months of age. Similar age-related declines were observed in dietary restricted animals but levels were generally 14-25% lower at each age group. IGF-1 mRNA levels demonstrated similar decreases with age in ad libitum fed animals, but in dietary restricted animals, levels plateaued at 22 and 28 months. IGF-1 binding protein analysis revealed 3 bands at approximate molecular weights of 40k, 30k, and 24k. All bands demonstrated a decrease in relative IGF-1-BP concentration with age, as well as a decrease in the 40k and 30k binding proteins after dietary restriction. These results indicate that (a) aging in ad libitum fed animals is associated with decreases in plasma IGF-1, IGF-1-BP, and IGF-1 mRNA levels; and (b) long-term dietary restriction decreases plasma IGF-1 and IGF-1-BP levels in each age group although the age-associated decreases in IGF-1 mRNA levels are prevented by dietary restriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of low- and high-protein diets on insulin and insulin-like growth factor-1 binding to skeletal muscle and liver in the growing rat

The influence of protein content of the diet on the plasma concentrations and binding to skeletal muscle and liver of insulin and insulin-like growth factor-1 (IGF-1), was studied in growing rats. Animals with a starting body-weight of 80 g received for an 11 d period isoenergetic diets containing (g/kg dry matter) 155 protein as controls (MP), or 55 (LP) or 300 (HP) protein. Food was offered as six equal meals/d. Daily food intakes provided adequate amounts of energy. Total plasma IGF-1 increased linearly as a function of dietary protein intake. Plasma insulin was lower in the LP than in the MP and HP groups. Hormone binding was studied in wheat-germ agglutinin (WGA) partially purified skeletal muscle receptor preparations. Each 125I-labelled hormone binding was competed for by increasing amounts of homologous and heterologous unlabelled hormone; this displacement needed lower concentrations of homologous than heterologous hormone. When compared with MP-diet feeding, the LP diet resulted in an increased ligand concentration for half-maximal binding. In addition the specific 125I-labelled insulin and 125I-labelled IGF-1 binding increased at all hormone concentrations and, as revealed by Scatchard analysis, the hormone binding capacity also rose (only significant for low-affinity insulin receptors and high-affinity IGF-1 receptors). The HP diet had little effect on hormone binding, except to increase insulin binding at very low insulin concentrations. Hormone binding was further studied in WGA partially purified liver receptor preparations. Those preparations did not exhibit any detectable specific 125I-labelled IGF-1 binding. The specific 125I-labelled insulin binding was not altered by dietary protein level. It is concluded that the increase in skeletal muscle insulin and IGF-1 binding along with a decrease in insulin and IGF-1 in the blood from rats fed on the LP diet, is consistent with the concept of an inverse relationship between plasma hormone and hormone binding. The physiological significance with respect to metabolic adaptation of muscle remains to be established.