Plasma Somatomedin Levels Research Articles

An investigation of the anabolic activity of somatropin in normal and burned rats

A ‘blind’, cross-over study was performed in 10 control and 12 burned rats which were assigned to receive either biosynthetic human growth hormone (somatropin) or placebo for 5 days each in random order. There was a significant use in urinary nitrogen excretion and rapid weight loss in the burned rats, which also had significantly lower plasma somatomedin levels than control rats. Somatropin administration resulted in a significant increase in somatomedin levels in control rats only. There was no significant difference in weight or nitrogen balance between somatropin or placebo-treated rats. It is concluded that rats with normal pituitary function are insensitive to the anabolic effects of somatropin and that burn injury abolishes the normal somatomedin response to somatropin.

Plasma somatomedin activity and diabetic retinopathy.

Somatomedin activity was measured by a rabbit chondrocyte bioassay in plasma of adult patients with insulin-dependent diabetes of 11-28 years duration. Mean somatomedin activity in patients with background or proliferative retinopathy, assessed by ophthalmoscopy or fluorescein angiography, was 1.42 +/- 0.65 U/ml (n = 20) which was significantly greater than in age- and weight-matched control subjects (1.05 +/- 0.22 U/ml, n = 9). In contrast, somatomedin activity was not raised in patients who had no retinopathy (1.16 +/- 0.33 U/ml, n = 10). Diabetic patients with retinopathy also showed the greatest differences between repeat samples suggesting wider fluctuations in plasma somatomedin levels. Plasma growth hormone and glucose measured either simultaneously with somatomedin or during a 12-24 h profile were not different when diabetics with or without retinopathy were compared. The somatomedins have mitogenic actions in vivo on a variety of connective tissues. The possibility that this may extend to retinal vessels should be further evaluated.

Insulin-infusion-pump treatment of diabetes: influence of improved metabolic control on plasma somatomedin levels.

We examined whether changes in somatomedin accompany those seen in glucose and growth hormone during treatment with the insulin-infusion pump. somatomedin levels in eight insulin-dependent diabetics (13 to 29 years of age) were measured before and after 16 weeks of outpatient insulin-pump treatment, which lowered mean glucose from 245 +/- 21 to 100 +/- 5 mg per deciliter and total glycosylated hemoglobin from 16.2 +/- 1.2 to 9.7 +/- 0.3 per cent (mean +/- S.E.M.). During conventional insulin therapy, both total somatomedin and somatomedin C were within the normal range, despite elevations in growth hormone. Pump treatment resulted in a 70 to 75 per cent increase in both total somatomedin and somatomedin C (P less than 0.05) and a fall in growth-hormone concentrations. In the two growing adolescents, growth velocity doubled during 13 to 15 months of pump treatment. Our data suggest that the improved insulin delivery or metabolic control increases somatomedin levels despite a decrease in growth hormone. Thus, insulin-pump treatment may be useful in optimizing growth in diabetic children.

Demonstration of normal plasma somatomedin concentrations in cystic fibrosis

WITH THE IMPROVEMENT in longevity in cystic fibrosis, retardation of skeletal growth has become a common manifestation 1, o and has been generally attributed to inability to meet the increased calorie demands of obstructive lung disease, chronic infection, and malabsorption. In protein-calorie malnutrition, which has been proposed as a model for the growth failure of CF, plasma somatomedin levels are usually low, often in the face of elevated levels of growth hormone? 7 It has been suggested that this suppression of SM generation represents the body's effort to shunt caloric and amino acid substrates away from general anabolic uses, so as to satisfy critical energy demands of vital organsY Lee et al have recently reported decreased bioassayable SM activity in six children with CF and have proposed that growth retardation in this disease is caused by a defect in the hypothalamic-pituitary-somatomedin generating system, secondary to protein malnutrition. The significance of these data may be questioned, however, because of

In vivo modulation of somatomedin receptor sites: effects of growth hormone treatment of hypopituitary children.

We have previously demonstrated that somatomedin (SM) can induce the loss of specific SMC receptors on cultured IM-9 lymphocytes in a time- and concentration-dependent manner. To investigate the acute regulation of SM binding under in vivo conditions, we have evaluated SM receptors on circulating mononuclear cells obtained from 12 hypopituitary dwarfs before and after 4 days of human GH administration (0.1 U/kg . day). Plasma SM levels, measured by radioreceptor assay, rose from 0.37 +/- 0.08 U/ml (mean +/- SEM) to 1.00 +/- 0.10 (P less than 0.001). Concomitantly, specific binding of [125I]SMC to 50 x 10(6) mononuclear cells/ml fell from 13.61 +/- 0.97% to 10.40 +/- 0.85% (P less than 0.02). The decrease in specific binding was predominantly secondary to a reduced number of SMC receptor sites per cell, with no alteration in receptor affinity. Overall, a significant inverse correlation was observed between plasma SM levels and mononuclear cellular binding of [125I]SMC (P less than 0.001). The data demonstrate that treatment of hypopituitary dwarfs with conventional therapeutic doses of human GH results in significant acute increases in plasma SM levels in the majority of subjects, with a reciprocal decline in the specific binding of [125I]SMC. We conclude that SM, like insulin, is capable of regulating homologous receptor concentrations under both in vitro and in vivo conditions.

1179 MODULATION OF SOMATOMEDIN RECEPTOR SITES IN GROWTH HORMONE-TREATED HYPOPITUITARY DWARFS

We have previously demonstrated that somatomedin (SM) can induce the loss of specific SM-C receptors on cultured IM-9 lymphocytes in a time- and concentration-dependent manner. To investigate the acute regulation of SM binding under in vivo conditions, we have evaluated SM receptors on circulating mononuclear cells obtained from 12 hypopituitary dwarfs prior to and after 4 days administration of hGH, 0.1 U/kg/day. Plasma SM levels, measured by radioreceptorassay, rose from 0.37 ± 0.08 U/ml (mean ± SEM) to 1.00 ± 0.10 (p< 0.001). Concomitantly, specific binding of 125-I-SM-C to 50 ×106 mononuclear cells/ml fell from 13.61 ± 0.97% to 10.40 ± 0.85% (p< 0.02). Scatchard analysis demonstrated that the decrease in specific binding was predominantly secondary to a reduced number of SM-C receptor sites per cell, with no alteration in receptor affinity. Overall, a significant inverse correlation was observed between plasma SM levels and mononuclear cell binding of 125-I-SM-C (r=-0.62, p< 0.001).The data demonstrate that treatment of hypopituitarism with conventional therapeutic doses of hGH results in significant acute increases in plasma SM levels in the majority of subjects, with a reciprocal decline in the specific binding of 125-I-SM-C. We conclude that SM, like insulin, is capable of regulating homologous receptor concentrations under both in vitro and in vivo conditions.

421 ACUTE SOMATOMEDIN RESPONSE TO GROWTH HORMONE THERAPY

We have examined the acute somatomedin (SM) response to growth hormone (GH) therapy in 21 GH deficient children using a placental membrane radioreceptor assay (RRA), which measures a variety of SMs, and a radioimmunoassay (RIA) specific for SM-C and insulin-like growth factor I (IGF-I). RRA and RIA SM determinations were performed on the same acid-chromatographed samples, obtained before initiation of therapy and 13 hr after each of 4 daily injections of GH (0.1 U/kg). The 4 days of GH therapy resulted in an increase in SM levels from 0.39±0.24(SD)U/ml to 1.18±0.62(SD) U/ml determined by RRA and 0.19±0.14(SD)U/ml to 0.82±0.51(SD)U/ml determined by RIA. A single injection of GH resulted in a significant rise in plasma SM levels measured by either RRA or RIA (p<0.001). Subjects who responded poorly to 2 injections of GH also had low SM levels after 4 days and even after 6 weeks of GH therapy. The RRA resulted in consistently higher values than the RIA, particularly when compared to a pure IGF-I/SM-C standard. SM peptide content determined by RRA and RIA were strongly correlated for individual subjects as well as for the whole group. However, the RRA/RIA ratio among individual subjects varied from 0.85 to 2.50. The marked difference in SM peptide content measured by RRA and RIA and the variability in the RRA/RIA ratio among individual subjects suggests that the IGF-I/SM-C RIA measures only one of a number of GH dependent SM peptides.

Normal somatomedin and somatomedin receptors in achondroplastic dwarfism.

It has been proposed that the basic abnormality in achondroplasia may be a quantitative defect in endochondral new bone formation secondary to decreased synthesis of somatomedin (SM) or abnormal binding of SM to specific receptors. To test this hypothesis, we have measured plasma SM levels and SM receptors on circulating mononuclear cells obtained from 5 achondroplastic dwarfs and 5 age-matched controls. Plasma SM levels were 0.82 +/- 0.14 U/ml (mean +/- S.E.M.) for the achondroplastic dwarfs and 0.90 +/- 0.12 U/ml for the controls. The specific binding of 125I-SM to 50 x 10(6) mononuclear cells was 7.66 +/- 1.11% for the dwarf group and 7.66 +/- 1.16% for the controls. Achondroplastic and control cells possessed equal numbers of receptor sites and identical receptor affinity for SM. The data indicate that plasma SM levels and SM binding to circulating mononuclear cells are normal in achondroplastic dwarfs and suggest a primary intrace-lular defect.

Somatomedin and Growth Hormone Studies

Plasma somatomedin (SM) activity and growth hormone (GH) concentration were measured in ten growth-retarded, well-nourished pediatric renal allograft recipients who received daily prednisone therapy. The SM activity ranged from 0.21 to 1.22 micron/mL, and it was subnormal in three patients. A significant correlation was found between SM activity and creatinine clearance. Serial SM levels were determined during a 24-hour period in five patients; SM activity decreased at six and 12 hours and returned to normal values by 24 hours. The 24-hour plasma GH concentrations ranged from 1.5 to 7.6 mg/mL. Peak GH concentrations ranged from 2.1 to 14.2 ng/mL after insulin-induced hypoglycemia and from 1.8 to 24.6 ng/mL after oral glucose loading. Sleeping GH peaks were absent in two patients. These results suggest that growth failure in renal allograft recipients who receive daily prednisone may result from (1) partial GH deficiency, (2) reduced SM levels owing to diminished allograft function, and (3) daily transient decrease in plasma SM levels after prednisone administration.

EFFICIENCY AND MODE OF ACTION OF CONJUGATED OESTROGENS IN THE TREATMENT OF TALL GIRLS

In 1972, we have reported on the successfull therapy of tall girls by continous administration of high doses of conjugated oestrogens, combined with an oral progestin for 5 days per month. This is a report on 23 such treatments, -in 14 cases With 7.5 mg Presomen (R) daily, in 9 cases with 4.5 mg Presomen In 9 cases the therapy has meanwhile been terminated. At the start these girls showed bone ages of 11 to 14 cm (x = 8.9km) This growth rate was reduced to 1.9 cm on the average for the first year. The growth reduction was 7.22 cm in the mean. In the second group, which we treated with 4,5 mg, we saw further growth between 2, 5 and 4,2 cm within the first six months under therapy. Hence we recommended treatment with a daily dose of 7.5 rag Presomen. Serious side effects were not encountered under this dosage. The almost abrupt growth stop under Presomen in spite of open epiphyseal lines caused us to investigate plasma somatomedin levels and growth hormone. After 4 to 6 months of treatment the soraatomedin levels, calculated as ratios of SM before and under therapy, were decreesed to ratios between 0.65−0.8 while GH secretion increased under therapy with Presoraen.

Primary somatomedin deficiency. Case report.

A child presenting with the clinical features of hyposomatotropism but with high immunoreactive plasma growth hormone is described. During short-term administration of human growth hormone (HGH) his response with regard to fasting blood-glucose and free fatty acids, plasma-somatomedin, urinary excretion of calcium, nitrogen, and hydroxyproline was minimal or absent. 6 months of treatment with HGH did not reduce the endogenous HGH secretion. Insulin secretion had not increased and plasma somatomedin levels remained extremely low. Over a period of 2 years of treatment, growth response and loss of subcutaneous fat were minimal. On serial dilution in radioimmunoassay, his growth hormone (GH) molecule yielded a parallel line with the HGH standard. In electrofocusing experiments the GH molecule was in the same <i>p</i>H range as growth hormone in acromegalic plasma and the major peak of clinical grade HGH (5·03 against 5·01 and 4·98). It is concluded that an overall and specific diminished responsiveness to HGH is present in this patient. This includes a lack of generation of somatomedin, which is thought to be the cause of his short stature. There was no evidence of abnormality of the GH molecule.