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At least 19 recordsLinked to original sources
PubMed1978

Comparison of [125I]somatomedin A and [125I]somatomedin C radioreceptor assays for somatomedin peptide content in whole and acid-chromatographed plasma.

The placental membrane radioreceptor assay was used to measure the levels of somatomedin (SM) peptides in plasma. Displacement of both [125I]somatomedin A ([125I]SM-A) and [125I]somatomedin C ([125I]SM-C) by normal whole plasma, the peptide fraction of acid-chromatographed plasma, and a partially purified, insulin-free SM preparation were compared. The peptide fraction of plasma was isolated by acid chromatography over Sephadex G-50 in 0.25 M formic acid with a yield of greater than or equal to 90%, as determined by bioassay and [125I]SM. In the case of [125I]SM-A, the dose-response curves for whole plasma, acid-chromatographed plasma, and the standard SM preparation were parallel (P less than 0.2). In contrast, for [125I]SM-C, the dose-response curves for acid-chromatographed plasma and the purified SM preparation were parallel (P less than 0.2), but both differed significantly from that of whole plasma (P less than 0.001). In addition, there was less variability in the assay of acid-chromatographed plasma compared to whole plasma. The results indicate that radioreceptor assay of unextracted normal plasma using [125I]SM-A is a valid measure of SM peptide concentration, while radioreceptor assay of unextracted normal plasma using [125I]SM-C, in our hands, is not. Acid chromatography of plasma before its assay is an uncomplicated procedure which allows valid and precise measurement of SM peptide content using either [125I]SM-A or [125I]SM-C.

Adult↗
PubMed1979

Further comparisons of the [125I]somatomedin A and the [125I]somatomedin C radioreceptor assays of somatomedin peptide.

The GH dependency of somatomedin (SM) peptide content in plasma was assessed using the placental membrane radioreceptor assay (RRA) to measure whole and acid-chromatographed plasma using both [125I]SM A and [125I]SM C. Plasmas from 10 normal children and adults, 11 GH-deficient children before and after therapy with 0.1 U/kg GH im daily for 5 days, and 10 acromegalic patients were assayed as well as a standard plasma pool from 20 healthy adult males. The results of these assays revealed that the SM content of plasma is GH dependent and that assay of whole and acid-chromatographed plasma with the [125I]SM A RRA and assay of acid-chromatographed plasma with the [125I]SM C RRA give comparable measurements of SM peptide content. There was a positive correlation of the [125I]SM A RRAs of whole and acid-chromatographed plasma from each patient (r = 0.87; n = 41; P much less than 0.001). An even stronger positive correlation was observed when the [125I]SM A and [125I]SM C RRAs of acid-chromatographed plasma were compared (r = 0.94; n = 41; P much less than 0.001). Furthermore, it was demonstrated that precise measurement of SM peptide content in plasmas from subjects with abnormal GH states and from normal subjects is enhanced by acid chromatography of the plasma before assay in either the [125I]SM A or [125I]SM C RRA.

Acromegaly↗
PubMed1979

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.

Animals↗
PubMed1979

Nutrition and somatomedin. V. Action and measurement of somatomedin inhibitor(s) in serum from diabetic rats.

Serum from normal rats stimulates growth cartilage in vitro; this stimulation is attributed to somatomedin activity. In contrast, serum from diabetic rats may produce dose-response lines with negative slopes and, in combination studies, suppress the stimulatory activity of serum from normal rats; this is attributed to somatomedin inhibitory factor(s). Somatomedin inhibitory activity in serum from diabetic rats cannot be attributed to recognized catabolic factors, such as glucocorticoids or free fatty acids. The inhibitory activity is resistant to 100 C heat at neutral pH but is partially removed by 100 C heat at pH 5.5. Somatomedin inhibitory activity can be estimated as the ability to decrease the stimulation of rat cartilage incubated for 2 days with serum from normal rats. With this method, serum from diabetic rats provides linear inhibition of both sulfate and thymidine uptake. This procedure is simple, reproducible, and allows detection of inhibitory activity in as little as 5 microliter whole serum. It allows identification of individual samples enriched in inhibitory activity and should be useful in further studies of somatomedin inhibitory factor(s).

Animals↗
PubMed1976

Nutrition and somatomedin. II. Serum somatomedin activity and cartilage growth activity in streptozotocin-diabetic rats.

Since diabetes mellitus is a condition in which poor growth occurs despite elevation of plasma GH, we have attempted to determine if poor growth in diabetes, as in malnutrition, could be associated with a decrease in somatomedin activity. Young male rats were rendered diabetic with intravenous streptozotocin (STZ). The growth activity of their cartilage was estimated by 35SO4 incorporation in vitro, and somatomedin (SM) activity in their serum was determined by the stimulation of SO4 incorporation by cartilage from hypophysectomized rats or normal young pigs. Cartilage growth activity was significantly decreased 24 hours after STZ and fell to hypopituitary levels after 48 hours. The decreased growth activity could not be attributed to decreased cartilage responsiveness to SM, since incubation of diabetic cartilage with normal rat serum (normal SM) resulted in significant stimulation of cartilage SO4 incorporation. SM in diabetic serum decreased to hypopituitary levels 24 hours after STZ, and decreased further after 48 hours. The decrease in SM and cartilage growth activity was not prevented by the administration of high doses of bovine GH. The fall in bioassayable SM appeared to be due in part to the presence of an SM inhibitor in the diabetic serum, since addition of diabetic serum to normal serum decreased to measurable SM in the normal serum. Administration of insulin to diabetic rats 48 hours after STZ led to significant increases in SM and cartilage growth activity, and insulin therapy 24 hours after STZ prevented the decreases in SM and cartilage growth activity which occurred without insulin. Thus, acute STZ-induced diabetes in rats was associated with a significant decrease in both serum SM and cartilage growth activity; these changes were not ameliorated by administration of GH, and insulin therapy could both prevent and reverse the fall in SM and cartilage growth activity. From these observations, we conclude that (1) that fall in somatomedin activity and cartilage growth activity associated with STZ-induced diabetes appears to be due to insulin deficiency and (2) growth failure in diabetes, as in malnutrition, may be due to decreased somatomedin activity.

Animals↗
PubMed1978

Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH.

Two three-year-old boys with dwarfism (height ages 1-4/2 and 1-11/12 years) and delayed bone ages (1-4/12 and 1-9/12 years) had normal growth hormone (GH) responses after stimulation and low levels of somatomedin. Unlike patients with Laron syndrome, the two patients generated normal levels of somatomedin after administration of exogenous hGH. Treatment with hGH (2 IU every other day) brought about a significant increase in the growth rate of both patients. The growth rate of the first patient increased from 2 cm/year before treatment to 12 cm/year on therapy. The growth rate of the second patient was 4.5 cm/year before treatment, and 8.3 cm/year while on treatment. The two cases represent a new syndrome of dwarfism which may be caused by secretion of a biologically inactive but immunoreactive GH.

Child, Preschool↗
PubMed1979

Purification of a basic somatomedin, from human plasma Cohn fraction IV-1, with physicochemical and radioimmunoassay similarity to somatomedin-C and insulin-like growth factor.

A basic somatomedin (SM) was purified from human plasma Cohn fraction IV-1 using an initial acid--ethanol--acetone extraction procedure followed by alternating molecular size or charge protein separation techniques. The final recovery of SM bioactivity was approximately 2% of that present in the starting Cohn fraction. The purified SM has an approximate molecular weight of 7500, pI 8.6, 4000 SM bioactivity units per milligram (as measured by a hypophysectomized rat bioassay) and a parallel approximately equipotent radioimmunoassay dose--response curve to SM-C and insulin-like growth factor-1 (IGF-I). Sodium dodecyl sulfate--polyacrylamide gel electrophoresis of this purified SM revealed a single protein band. The preliminary determination of the amino acid sequence of the N terminus suggested that this SM preparation was over 75% pure and the first five N-terminal amino acids were identical with those of IGF-I.

Amino Acids↗
PubMed1979

Radioimmunoassay of a basic somatomedin: comparison of various assay techniques and somatomedin levels in various sera.

Purification of a basic somatomedin (SM), with similarity to SM-C and insulin-like growth factor, from human plasma Cohn fraction IV-1 enabled development of a RIA based on this SM.SM antiserum was produced by immunizing rabbits with partially purified SM. This antiserum (final dilution, 1:50,000) specifically bound approximately 40% of added [125I]-SM in this RIA. The RIA sensitivity was 2 x 10(-4) U immunoreactive SM (IRSM). Highly purified SM-C, insulin-like growth factor 1, and our SM revealed parallel and approximately equipotent dose-response curves in this RIA; rat SM and multiplication stimulation activity revealed less cross-reactivity. IRSM was detected in sera of all species tested except fish. Acidification of sera, without subsequent chromatography, before assay permitted measurement of total IRSM with either an equilibrium or nonequilibrium RIA technique. Acidification of serum appears to increase SM-binding capacity while decreasing binding affinity of the 20,000--50,000 mol wt proteins in serum. The mean (+/- SEM) IRSM concentrations in sera from normals and patients with acromegaly, hypopituitarism, GH deficiency before/after treatment, and Laron dwarfism were 1.45 +/- 0.17, 5.49 +/- 0.48, 0.19 +/- 0.07, 0.10 +/- 0.02/0.64 +/- 0.45, and 0.25 +/- 0.11 U/ml, respectively, compared to a pooled normal human serum reference standard which was designated to contain 1 IRSM U/ml. Measurements of total IRSM (bound and free) in serum may not accurately reflect SM bioactivity and will require interpretative caution.

Acromegaly↗
PubMed1976

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.

Animals↗
PubMed1979

Growth impairment with elevated somatomedin levels in children with chronic renal insufficiency.

In children with chronic renal insufficiency serum levels of somatomedin measured by radioreceptor assay were found to be strikingly elevated and were in the same range as in acromegaly in spite of decreased growth. The serum somatomedin level was inversely correlated with renal function and children on haemodialysis had the highest values. The elevated somatomedin was most likely due to progressive destruction of the kidney, the primary catabolic site for somatomedin and other polypeptides. After successful transplantation the somatomedin values fell to slightly above normal even though growth was still impaired. Using a bioassay based on the mitogenic property of somatomedin, a lower than normal rather than an increased level was found in chronic renal insufficiency suggesting that in uraemia an inhibitor to somatomedin bioactivity was present. It is concluded that the cause of the growth failure in chronic renal insufficiency and after transplantation is not due to a lack of somatomedin, but an inhibitor to its action could be a factor. It would appear that a normal somatomedin may be necessary for normal growth, but it is not sufficient.

Adolescent↗
PubMed1979

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.

Animals↗
PubMed1979

Immunoreactive somatomedin B in acromegaly and in Turner's syndrome.

Serum somatomedin B was measured by radioimmunoassay in forty-seven normal subjects, twenty-nine patients with acromegaly before and twenty-four after treatment, and eighteen patients with Turner's syndrome. Somatomedin B levels were significantly elevated in untreated acromegaly and in Turner's syndrome compared with the control group; they decreased following treatment of acromegaly. Because of the overlap between the groups, little information could be obtained from single somatomedin B estimations, which could, therefore, not replace dynamic tests of growth hormone secretion. No correlation between growth hormone and somatomedin B in acromegaly was detected; however, somatomedin B appeared to be related to the insulin response during the oral glucose tolerance test. In Turner's syndrome, no relationship between somatomedin B and insulin production, urinary oestrogen excretion, growth hormone secretion, gonadotrophin levels, age or height was found. The reason for the raised somatomedin B levels in Turner's syndrome remains at present unknown.

Acromegaly↗
PubMed1976

Binding of somatomedins and insulin to plasma membranes prepared from rat and monkey tissue.

Particulate membranes prepared from a variety of monkey and rat tissues were shown to have specific binding sites for somatomedin A. Binding to talc on the other hand showed no specificity, and the sensitivity was less. The membrane-bound somatomedin A was displaced by somatomedin A in concentrations between 0.01 and 5 U/ml. Of the other hormones tested only insulin in high concentrations could interfere with the binding of labelled somatomedin A to tissue membranes. Membranes prepared from a number of rat and monkey tissues also contained binding sites for insulin. Somatomedin A could interfere with the binding of labelled insulin. No binding was observed for somatomedin B in the tissues studied.

Animals↗
PubMed1979

Evaluation of acromegaly by radioimmunoassay of somatomedin-C.

We measured serum concentrations of somatomedin-C by radioimmunoassay in 57 acromegalic patients and compared them with various indicators of disease activity. The mean fasting somatomedin-C concentration was 6.8 U per milliliter (range, 2.6 to 21.7) for the acromegalics and 0.67 U per milliliter (range, 0.31 to 1.4) for 48 normal, fasting adults. The somatomedin-C concentration correlated significantly with: heel-pad thickness (r = 0.73), fasting glucose (r = 0.74), and one-hour postprandial glucose (r = 0.77). In contrast, "glucose-suppressed" growth hormone correlated weakly (r = 0.34, 0.36, 0.34) with these clinical indexes of severity. Fasting growth hormone levels showed no correlation (r = 0.14). Five active acromegalics had "normal" growth hormone levels after glucose suppression, but they had elevated somatomedin-C. In 15 patients studied one year after treatment, changes in somatomedin-C concentrations paralleled the degree of clinical improvement. Measurement of somatomedin-C appears to provide a reliable means for confirming the diagnosis of acromegaly and of clinical disease activity than measurement of growth hormone concentrations.

Acromegaly↗