Somatomedin-binding Protein Research Articles

Studies of insulin-like growth factor -I and -II by specific radioligand assays in umbilical cord blood.

Somatomedin concentrations in human umbilical sera (n = 206) were measured using a specific radioimmunoassay for insulin-like growth factor (IGF)-I and a specific radioreceptor assay for IGF-II following acid-ethanol extraction of the sera to remove the somatomedin binding proteins. IGF-I concentrations were lower (P less than 0.001) than adult values and correlated with gestational age (P less than 0.001) and birth weight (P less than 0.0001). Multiple regression analysis demonstrated that both birth weight expressed independently of gestational age as the standard deviate score (P less than 0.0001) and gestational age (P less than 0.002) had effects on umbilical cord IGF-I concentrations. IGF-II concentrations were similar to adult values and did not correlate with gestational age, birth size or IGF-I values. IGF-II concentrations were higher (P less than 0.005) in male than female fetuses. These data support a role for IGF-I in influencing fetal growth and suggest the independent regulation of the secretion of IGF-I and II in the perinatal period. These was no evidence to suggest a distinct perinatal form of somatomedin.

Pulsatility of immunoreactive somatomedin-C in chronically cannulated rats.

Pituitary GH secretion is pulsatile in man and the rat, but evidence of pulsatility in the GH-dependent somatomedins (insulin-like growth factors) has not been described. In this study serum immunoreactive somatomedin-C periodicity was examined in 10 chronically cannulated unstressed rats. Blood samples were taken at 15-min intervals over 6 h, and serum rat GH and somatomedin-C measured by RIA. For somatomedin-C assay samples were first extracted into acid-ethanol to dissociate protein-bound peptide. Serum GH levels indicated episodic secretion, with a frequency of 2.85 +/- 0.24 h; some secretory episodes were polyphasic. The mean frequency of all GH spikes reaching 400 ng/ml or greater was 1.99 +/- 0.87 h. Somatomedin-C levels showed fluctuations over an average 2-fold concentration range, 0.60 +/- 0.20 to 1.21 +/- 0.29 U/ml (mean, 0.86 +/- 0.18 U/ml), with peaks occurring 1-1.5 h after most GH secretory peaks. The somatomedin-C peak frequency was 1.93 +/- 0.47 h. Summed GH values from 0-5 h were significantly correlated with summed somatomedin-C values from 1-6 h (r = 0.861, P = 0.0007), suggesting a 1-h lag between GH pulses and the following rise in somatomedin-C. Somatomedin-binding protein showed no regular fluctuations. This study indicates that serum somatomedin-C levels in unstressed rats show periodicity which may be directly related to pulsatile GH secretion.

Uremia reduces serum insulin-like growth factor I, increases insulin-like growth factor II, and modifies their serum protein binding.

Because uremia is associated with growth failure in children, serum levels of somatomedins have been studied in patients by bioassay, radioreceptor assay (RRA), and RIA. While bioassays have indicated low levels of somatomedin, RRA and RIA of native serum have been elevated. We reinvestigated this topic by insulin-like growth factor I (IGF-I) RIA and insulin-like growth factor II (IGF-II) specific rat placental membrane RRA. Sera were extracted with acid-ethanol, which recovers somatomedins and excludes somatomedin-binding proteins (SBP). Results are expressed as the relative potency compared to a normal human reference serum. The result of a serum IGF-I RIA of 22 adult patients undergoingchronic hemodialysis was 0.41 ° 0.05 U/ml (mean ° SE). Limits of normal adult sera are 0.58 and 1.84 U/ml. In contrast, the result of the IGF-II RRA was markedly elevated (3.9 ° 0.3 U/ml). Limits of normal adult serum are 0.39and 1.05 U/ml. To determine available serum binding protein, we incubated 2, 10, 25, and 100 /xl...

Structure of somatomedin-binding protein: alkaline pH-induced dissociation of an acid-stable, 60,000 molecular weight complex into smaller components.

The association of somatomedin (Sm) peptides with their specific serum binding proteins (SmPBs) and the preservation of SmBP integrity are both pH dependent. Acid extracts of human plasma Cohn fraction IV-4 chromatographed at pH 5.0 after incubation with [125I]iodoinsulin-like growth factor I yield predominantly a 60,000 molecular weight complex of specifically bound radiolabeled peptide. Alkaline exposure (pH 8.0) of either the initial acid extract of Cohn fraction IV-4 or the isolated 60,000 molecular weight chromatographic peak shifts the recovery of bound [125I]iodoinsulin-like growth factor I on rechromatography to two smaller complexes of approximately 46,000 and 30,000 molecular weight. These results support the existence of two or more forms of human plasma SmBP that may possess a common 30,000 molecular weight component.

Development of a heterologous radioimmunoassay for somatomedin C in sheep blood.

A heterologous radioimmunoassay for the measurement of somatomedin C in sheep serum has been developed using purified 125I-labelled human somatomedin C and an antiserum to human somatomedin C. It was observed that the GH dependence of somatomedin C could not be verified when unprocessed sheep sera were assayed, because of interference by somatomedin binding proteins. After incubation of samples at pH 3.8, however, concentrations of somatomedin C mirrored GH status. Assays results from sera after prolonged exposure to acid agreed with results from which had undergone acidification and gel chromatography. Using the methods developed in this study, 12 sera from normal sheep had a mean concentration of somatomedin C of 2.35 +/- 0.27 (S.E.M.) units/ml while nine sera from hypophysectomized sheep contained 0.45 +/- 0.04 units/ml (P less than 0.001), and one serum from a ewe with a prolonged GH excess associated with a pituitary tumour had a value of 6.9 units/ml. The radioimmunoassay resulting from these studies should provide a tool for investigation of the physiological control of somatomedin C in sheep.

Somatomedin binding proteins in GH deficient children with normal somatomedin

Somatomedin-C/insulin-like growth factor-I(SM) circulates in plasma bound to a large molecular weight (150K) GH dependent protein complex (SM-BP). There is also a smaller (38K) non-GH dependent protein which binds exogenous radiolabeled SM. Although SM is GH dependent, children with certain nutritional disturbances show a dissociation between GH and SM. SM-BP was studied in 3 children with normal SM (by RIA) and normal growth rate inspite of documented GH deficiency. All are hyperphagic and obese; 2 are status-post craniopharyngioma resection; the third has arrested hydrocephalus. Insulin responses to oral glucose were elevated but prolactin levels were not. [125I] SM (20,000 cpm) was incubated (4°, 16 hrs) with 1 ml of plasma. The mixture was subjected to gel filtration (2.6 × 80 cm, Sephacryl-200, 0.1 M Tris, 5mM EDTA, pH 7.4). Endogenous SM eluted at Ve/Vo of 1.2-1.25 (≃150K). Some [125I] SM also eluted in this region while the major portion eluted at Ve/Vo of 1.5 (≃40K). This pattern of endogenous and [125I] SM was identical to that seen in normal adults and hyposomatotropic children on GH. These results indicate that 150K SM-BP is regulated in parallel with SM in those instances when SM and GH are discordant. Such closely coordinated regulation might be accomplished if SM and SM-BP were synthesized together.

The growth hormone dependence of a somatomedin-binding protein in human serum.

We previously reported that a serum somatome-din (SM)-binding protein is GH dependent in the rat. We now show that a similarly sized SM-binding protein in humans is also GH dependent. Multiplication-stimulating activity (MSA), purified from medium conditioned by the BRL-3A rat liver cell line, was radioiodinated and used as a human SM analog for these studies. A normal human serum pool and sera obtained from nine GH-deficient patients before and after GH treatment were gel filtered on Sephadex G-200 in 0.05 M NH4HCO3. Specifi c [l25I]MSA-binding activity was measured in each column fraction. When pre-GH sera were gel filtered over Sephadex G-200, specific [I25I]MSA-binding activity was low and eluted in the γ-globulin region (peak II), in the albumin region (peak III), or in both depending upon the patient. After GH treatment, specific [125I]MSA binding increased dramatically and was always found primarily in peak II, resembling the pattern for normal human serum. For three patients, Sephadex G-200 column pools were chromatographed on Sephadex G-50-1 M acetic acid to dissociate and separate binding protein from SM activity. SM activity was measured by a [3H]thymidine incorporation assay in chick embryo fibroblasts and by a competitive protein-binding assay using rat serum binding protein. SM activity coeluted with specific [l25I]MSA-binding activity on Sephadex G-200 gel filtration of normal, pre-GH, and post-GH sera and was higher in column fractions from post-GH and normal sera than from pre-GH sera. To determine whether [l25I]MSA-binding activity measurements on Sephadex G-200 column fractions reflected the distribution of binding capacity, Scatchard analysis of MSA binding to stripped binding protein was performed on Sephadex G-200 pools that had been gel filtered on Sephadex G-50-1 M acetic acid. The maximal binding capacity was found in the Sephadex G-200 column fractions identified by the highest [125I]MSA binding activity. Binding capacities of peak II binding protein increased several-fold after GH treatment. We conclude that the level of a γ-globulin-sized SM-binding protein is GH dependent in humans.

Plasma somatomedin-binding proteins in hypopituitarism: changes during growth hormone therapy.

The somatomedin (SM) peptides are carried in plasma complexed to specific SM-binding proteins (SMBPs). In addition to the SMBP in the complex, there is an unsaturated SMBP in plasma in which the SMBP is not occupied by SMs. We have compared levels of unsaturated SMBP in 7 normal adults to those in 21 children with GH deficiency before and during treatment with hGH (0.1 U/kg.day) for 4 days. In addition, the SM-C/insulin-like growth factor I (IGF-I) content of each plasma was measured by RIA. There was a significant (P less than 0.01) difference in unsaturated SMBP levels between normal controls (17.8 +/- 0.8% bound/20 microliters) and untreated hypopituitary patients (27.8 +/- 2.2% bound/20 microliters). Thus, a lower SM-C/IGF-I content was associated with a higher unsaturated SMBP level. Furthermore, there was a significant negative correlation between SM-C/IGF-I content and unsaturated SMBP in untreated hypopituitary patients (r = 0.73; P less than 0.0001). Treatment with hGH normalized the mean unsaturated SMBP level in hypopituitary patients within 2 days. Full displacement curves and Scatchard analysis showed that the increased unsaturated SMBP level in hypopituitary plasma was entirely due to an increased affinity (8.4 X 0.9 X 10(-10) M) compared to normal (2.3 X 0.2 X 10(-9) M). A higher affinity form of unsaturated SMBP is uniquely present in hypopituitarism and disappears with hGH treatment. The measurement of this unsaturated SMBP mirrors the SM peptide content.

Identification of a somatomedin-binding protein produced by a rat hepatoma cell line

FEBS LettersVolume 127, Issue 2 p. 225-227 Full-length articleFree Access Identification of a somatomedin-binding protein produced by a rat hepatoma cell line Dan H. Morris, Dan H. Morris Division of Endocrinology, University of Colorado Health Sciences Center, Denver, CO 80262, USASearch for more papers by this authorDon S. Schalch, Don S. Schalch Division of Endocrinology, University of Colorado Health Sciences Center, Denver, CO 80262, USASearch for more papers by this authorBarbara Monty-Miles, Barbara Monty-Miles Division of Endocrinology, University of Colorado Health Sciences Center, Denver, CO 80262, USASearch for more papers by this author Dan H. Morris, Dan H. Morris Division of Endocrinology, University of Colorado Health Sciences Center, Denver, CO 80262, USASearch for more papers by this authorDon S. Schalch, Don S. Schalch Division of Endocrinology, University of Colorado Health Sciences Center, Denver, CO 80262, USASearch for more papers by this authorBarbara Monty-Miles, Barbara Monty-Miles Division of Endocrinology, University of Colorado Health Sciences Center, Denver, CO 80262, USASearch for more papers by this author First published: May 18, 1981 https://doi.org/10.1016/0014-5793(81)80210-4Citations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume127, Issue2May 18, 1981Pages 225-227 ReferencesRelatedInformation

416 SOMATOMEDIN BINDING PROTEIN IN GROWTH HORMONE DEFICIENCY

The somatomedin (SM) peptides are carried in plasma complexed to SM binding proteins (SMBP). The SM complexes have two major forms in plasma. The 150K dalton complex is made up of three subunits: an acid stable SMBP, SM peptide, and an acid labile component. The 40K complex is made up of a SMBP and SM peptide In addition, there is unsaturated SMBP found mainly in the 35-40K region. We have compared levels of unsaturated SMBP in 7 normal adults to 21 children with growth hormone deficiency before and during treatment with hGH 0.1U/Kg/day 4 days. The SM-C/IGF-I content of each plasma was measured by RIA. There was a significant (p< 0.01) difference in unsaturated SMBP between normal controls (17.8±0.8 %Bound/20ul) and untreated hypopituitary patients (27.8±2.2 %Bound/20ul). Thus a lower SM-C/IGF-I was associated with a higher unsaturated SMBP. Furthermore, there was a significant negative correlation between SM-C/IGF-I content and unsaturated SMBP in the untreated hypopituitary patients (r=0.73, p< 0.001). Treatment with hGH normalized the mean unsaturated SMBP in the hypopituitary patients within two days. Full displacement curves and Scatchard analysis showed that the increased unsaturated SMBP in hypopituitary plasma was entirely due to an increased affinity (8.4±0.9 × 10−10M) when compared to normal (2.3±0.2 × 10−9M). We conclude that a higher affinity form of unsaturated SMBP is uniquely present in hypopituitarism which disappears with GH treatment. This change is in contrast to the low levels of acid stable SMBP which increase after GH.

Estradiol treatment of acromegaly Reduction of immunoreactive somatomedin-C and improvement in metabolic status

Administration of estrogens to acromegalic patients has been shown to reduce the serum concentrations of bioassayable somatomedin and to cause improvement in clinical status. These effects appear not to result from an effect on the secretion of growth hormone since growth hormone concentrations are not consistently reduced. Using a sensitive radioimmunoassay for somatomedin-C, we have assessed the relationship between the estrogen-induced reduction of somatomedin-C and changes in several indices of disease activity in five acromegalic patients. Statistically significant reductions in serum somatomedin-C(p < 0.02), urinary hydroxyproline (p < 0.05) and the phosphate clearance ratio (p < 0.01) occurred within three days of the institution of treatment with 1 mg ethylnyl estradiol daily. Unlike the consistent reduction in serum somatomedin-C erratic changes in growth hormone were observed. The decline in serum somatomedin-C was not due to an estrogen-induced increase in somatomedin-binding proteins since total serum somatomedin-C concentrations measured after treatment of serum with acid also were reduced by estrogen therapy, and the magnitude of this reduction was equivalent to that observed in untreated serum. The study indicates that the reduction of immunoreactive somatomedin-C correlates with estrogen-induced improvement in the metabolic activity of acromegalic patients and suggests that measurement of somatomedin-C may be useful in monitoring the effects of other drugs on this disease.

Ontogeny of somatomedin during development in the mouse: Serum concentrations, molecular forms, binding proteins, and tissue receptors

The purpose of this study was to assess the ontogeny of serum concentrations and molecular forms of somatomedin during fetal and postnatal development and to define the changes in serum binding proteins for somatomedin-C during various stages of development. The finding that fetal, placental, and decidual mouse tissues possess receptors for somatomedin suggests a role for somatomedin in fetal growth and possibly in the maintenance of pregnancy. Serum somatomedin-C was measured using a highly specific, heterologous radioimmunoassay (RIA) and a less specific membrane binding assay (MBA) which is more sensitive to the influence of somatomedins other than somatomedin-C. The assays were validated for mouse serum by showing that serum concentrations were reduced in genetically growth hormone-deficient mice and in hypophysectomized mice and were increased by growth hormone therapy. As in the human, the RIA measures only a portion of the somatomedin-C present in mouse serum. This “covering up” of somatomedin is attributed to the presence of serum binding proteins and is corrected by treatment of serum samples with acid. By both RIA and MBA, serum somatomedin concentrations are low in fetal and newborn mice, begin to rise in the fourth postnatal week, and reach adult values by 7 weeks of age. The chromatographic pattern of adult mouse serum on Sephacryl 200 is similar to that observed with human sera: The immunoreactive material elutes at apparent molecular weights of 140,000 and 30,000–40,000. The elution profile of 125I-labeled somatomedin-C bound to components of serum is nearly identical to the pattern of endogenous activity. As with human serum, somatomedin-C in acidified mouse serum elutes at a lower molecular weight, coincident with insulin and purified somatomedin-C. Maternal serum somatomedin declines in the last half of gestation at the time when placental lactogen levels rise. Along with the absolute decline in somatomedin content is the appearance of unsaturated sites on somatomedin binding proteins. These findings are unexpected and unexplained since somatomedin rises late in pregnancy in humans and several lines of evidence suggest that placental lactogen has the capacity to stimulate somatomedin production. We previously have presented evidence that explants of multiple fetal mouse tissues synthesize somatomedin-C. The present study shows that the immunoreactive somatomedin-C in fetal mouse serum shares identical characteristics with those reported previously for media obtained from mouse liver explants. It seems possible that somatomedin's actions are exerted primarily at or near its site of production and that circulatory levels do not reflect the importance of somatomedin-C on fetal growth. While elucidation of the dramatic developmental changes in serum content and molecular forms of somatomedin-C and in somatomedin binding proteins may be essential to clarifying the role of somatomedin on fetal growth, proof that somatomedin stimulates fetal growth will depend in large part on studies of its biological actions on fetal tissues.

Increased levels of multiplication-stimulating activity, an insulin-like growth factor, in fetal rat serum.

Multiplication-stimulating activity (MSA), purified from medium conditioned by the BRL-3A rat liver cell line, previously has been shown to be closely related to the human somatomedins or insulin-like growth factors. A radioimmunoassay was utilized to measure MSA levels in sera from fetal, maternal, and young rats. A serum somatomedin-binding protein was found to interfere in the radioimmunoassay by competing with antibody for binding 125I-labeled MSA. Therefore, prior to radioimmunoassay, sera were filtered on Sephadex G-75 in 1 M acetic acid to dissociate and separate somatomedin activity from the binding protein. Concentrations of MSA by radioimmunoassay were 20- to 100-fold higher in feta rat sera (1.8-4.4 micrograms/ml) than in maternal sera. MSA levels gradually decreased after birth, reaching maternal levels by day 25 of extrauterine life. MSA concentrations in feta rat sera also were found to be correspondingly high by a rat liver membrane radioreceptor assay and a competitive binding protein assay using rat serum somatomedin-binding protein. The findings of higher levels of MSA in fetal than in maternal rat sera and the gradual decline in MSA serum concentrations after birth are in direct contrast to total somatomedin activities measured by biosassay. Thus, MSA may function as a growth factor in the fetal rat whereas other somatomedins may play a role in stimulating growth during extrauterine life.

Purification and characterization of multiplication-stimulating activity. Insulin-like growth factors purified from rat-liver-cell-conditioned medium.

Multiplication-stimulating activity (MSA) refers to a family of insulin-like growth factors that have been purified from serum-free medium conditioned by a Buffalo rat liver cell line (BRL-3A). Using Dowex ion-exchange chromatography, gel chromatography on Sephadex G-75, and preparative disc acrylamide gel electrophoresis, several polypeptides with the full biological multiplication-stimulating activity have been isolated. One of these polypeptides, designated MSA II-1, previously has been used to study the relationship of the activity to the insulin-like growth factors (somatomedins) purified from human plasma. Polypeptide II-1 is a single chain polypeptide of molecular weight 8700. Glycine is the COOH-terminal amino acid. Edman degradation of carboxymethylated MSA II-1 did not reveal a free NH2-terminus. A polypeptide of lower molecular weight than MSA II-1 has also been purified. This polypeptide (MSA III-2) has been shown to be more potent than MSA II-1 in the rat-liver-membrane radioreceptor assay and in a competitive binding assay utilizing the rat-serum somatomedin-binding protein(s). The relationship of these various polypeptides has been investigated by gel filtration in guanidine hydrochloride and by acrylamide gel electrophoresis of the reduced and native polypeptides.

Characterization of a somatomedin (insulin-like growth factor) synthesized by fetal rat liver organ cultures.

Explants of 19- to 20-day fetal rat liver synthesize polypeptides biochemically and immunologically related to the well characterized somatomedin (insulin-like growth factor) BRL-MSA, multiplication-stimulating activity. Fetal MSA was purified from media conditioned by fetal liver explants by chromatography on Sephadex G-75 under acid conditions. Partially purified fetal MSA: 1) inhibited the binding of BRL-MSA to the MSA receptor of rat liver plasma membranes, to somatomedin-binding proteins from rat serum, and to rabbit anti-BRL-MSA serum; 2) had a molecular weight of 4,500 to 12,500 determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; 3) stimulated the incorporation of [3H]thymidine into the DNA of chick embryo fibroblasts and induced cell multiplication; 4) stimulated glucose oxidation in rat adipocytes and weakly inhibited the binding of insulin to the insulin receptors of IM-9 lymphocytes; and 5) stimulated sulfate uptake in costal cartilage from hypophysectomized rats. These activities were associated with the same molecular species in fetal MSA preparations following disc acrylamide electrophoresis and co-migrated with active BRL-MSA peptides.

Erratum

In the article, “Further Characterization of Growth Hormone-Dependent Somatomedin-Binding Proteins in Rat Serum and Demonstration of Somatomedin-Binding Proteins Produced by Rat Liver Cells in Culture,“ the list of authors and their affiliations should have appeared on the title page

Decrease in Serum Receptor-Reactive Somatomedin in Diabetes

Somatomedin in rat serum has been measured by a sensitive radioreceptor assay using 125I-labelled human somatomedin and human placental membrane. In rats made diabetic with strepotzotocin, receptor-reactive somatomedin levels were decrease by up to 75%. The decrease followed the time course of increasing serum glucose and occurred to the same extent in rats aged between 4 and 40 weeks. Endogenous serum receptor-reactive somatomedin appeared exclusively in high molecular weight fractions on gel chromatography. In diabetes the decreased somatomedin was due to a fall in this high molecular weight activity, but was not accompanied by a fall in somatomedin binding protein. These results suggest a role for insulin in maintaining serum somatomedin levels.

Further Characterization of Growth Hormone-Dependent Somatomedin-Binding Proteins in Rat Serum and Demonstration of Somatomedin-Binding Proteins Produced by Rat Liver Cells in Culture*

The somatomedin-like peptide multiplication-stimulating activity (MSA) binds specifically to rat serum. The pattern of MSA binding is GH dependent. Specific binding of [125I]iodo-MSA in normal rat serum is primarily in the gamma-globulin region (peak II) on Sephadex G-200, while MSA binding in hypophysectomized (hypox) rat serum is near the albumin region (peak III). This study further characterizes the peak II and peak III somatomedin-binding proteins produced by rat liver cells in culture. [125I]Iodo-MSA binding to normal rat serum is abolished by trypsin pretreatment of rat serum, suggesting that MSA binds to protein components of serum. The only detectable somatomedin activity (measured by [3H]thymidine incorporation into chick embryo fibroblast DNA) in fractions of normal rat serum chromatographed on Sephadex G-200 coincides with peak II binding of [125I]iodo-MSA. In hypox rat serum, the majority of detectable somatomedin activity is in the peak III region. There is complete displacement of the human somatomedins [125I]iodoinsulin-like growth factor I and II and [125I]iodosomatomedin A from the rat serum-binding sites by unlabeled MSA, suggesting that the human somatomedins bind to the same sites as MSA. Treatment of normal rat serum with 1 M acetic acid dissociates somatomedin activity from its binding proteins and converts somatomedin-binding proteins from peak II to peak III. Scatchard analysis of competitive binding data using [125I]iodo-MSA yields a binding affinity that is not appreciably different for either normal or hypox rat sera. The binding capacity of normal or acid-treated normal rat serum for MSA is significantly greater than that for comparably treated hypox rat sera. Although the site of synthesis of somatomedin-binding proteins in vivo is unknown, specific somatomedin-binding proteins are synthesized by two rat liver cell lines in culture. These rat liver cell somatomedin-binding proteins have the same molecular size and the same binding affinity for MSA as the peak III somatomedin-binding protein(s) in rat serum.

Somatomedin-C Receptor Ontogeny and Levels in Porcine Fetal and Human Cord Serum

The ontogeny of somatomedin receptors in tissues of fetal pigs and levels of somatomedin-C in fetal pig serum at various gestational ages and in human cord serum was investigated. Specific binding of 125I somatomedin-C by particulate membranes prepared from fetal organs from a variety of gestational ages almost always exceeds specific 125I insulin binding. In liver, kidney, heart and the maternal portion of the placenta, apparent binding affinity for somatomedin is relatively constant throughout gestation and is the same for membranes from fetal and adult animals. In contrast, in the fetal portion of the placenta, specific somatomedin-C binding and apparent binding affinity increases as gestation progresses. The changes in this tissue correlate temporally with the acceleration of growth of the pig fetus. Membranes prepared from fetal lungs exhibit higher specific binding of somatomedin and higher affinity constants than adult lung membranes. Somatomedin levels in fetal pig serum are about 25% of those observed in the sow and are constant throughout fetal life. Somatomedin in human cord serum is likewise low compared to adult levels. Small-for-gestational age infants and large, postmature infants have lower mean somatomedin levels than normal weight, full-term infants. The identification of specific somatomedin receptors in fetal tissues opens the possibility that somatomedin-C stimulates growth of the fetus. Although not resolved, the relatively low levels of somatomedin in fetal serum may reflect low levels of the somatomedin binding protein rather than an absolute deficiency of biologically active somatomedin.