Alteration of Cartilage Glycosaminoglycan Protein Acceptor by Somatomedin and Cortisol

Kilgore, B S; McNatt, M; Meador, S; Lee, J A; Hughes, Edwin R.; Elders, M. Joycelyn

doi:10.1203/00006450-197902000-00002

Cited by 26 publications

(8 citation statements)

References 10 publications

(15 reference statements)

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“…It has recently been shown that the restricted SM activity of sera with high concentrations of glucocorticoids could be returned to normal by prior treatment of the sera with charcoal, which adsorbs glucocorticoids (45). Apart from their short term effects (one example of which is reduced cartilage sulfation), evidence of the long term effects of glucocorticoids on cartilage, both biologically and histologically, has also been reported (19)(20)(21). These data, together with the present findings, indicate that the retarded growth accompanying excesses of glucocorticoid results not from a deficiency of SM but from impaired cartilage metabolism.…”

Section: Discussionsupporting

confidence: 67%

See 1 more Smart Citation

Serum Somatomedin/Insulin-Like Growth Factor (IGF) and IGF Carrier Levels in Patients with Cushing's Syndrome or Receiving Glucocorticoid Therapy*

Gourmelen

Girard

Binoux

1982

The Journal of Clinical Endocrinology & Metabolism

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Serum levels of somatomedin (SM)/insulin-like growth factor (IGF) and IGF carrier (IGF CP) have been determined in 49 patients with Cushing's syndrome before and/or after treatment and in 11 subjects under glucocorticoid therapy.Serum samples were gel filtered in acetic acid in order to separate IGFs from their carriers. IGF content was measured by a competitive protein-binding assay using the specific IGF CP produced by rat liver in culture and human IGF ([ 125 I]IGF I as tracer and a partially purified IGF preparation as standard). IGF CP concentration was assessed in terms of IGF CP binding to labeled IGF, compared to a reference IGF CP preparation obtained from human serum. Results are expressed in comparison with a pool of normal adult serum arbitrarily assigned values of 1 U IGF and 1 U IGF CP per milliliter.The mean IGF level for 39 untreated patients with Cushing's syndrome was 0.99 ± 0.06 (SEM) U/ml, which does not differ from normal adult values (1.05 ± 0.03). Nevertheless, 9 of these patients had subnormal values. For the 14 children or adolescents included in this group, the values observed fell within the range of the controls of the same age, although the growth rate determined for 10 of these patients averaged 1.4 cm/yr.The mean IGF CP level for the untreated patients was 0.78 ± 0.64 U/ml, which is significantly lower than that ol controls.(1.03 ± 0.05; P < 0.001).No correlation was found between IGF or IGF CP levels and parameters reflecting the severity of the hypercortisolism. In the 23 patients investigated after treatment, IGF and IGF CP levels fell within the range of normal values.For the 11 subjects under glucocorticoid therapy the mean IGF and IGF CP levels were no different from control values.Sulfation assays were carried out on the same serum samples as those used for the IGF determinations in 21 of the untreated patients with Cushing's syndrome. The mean SM activity (0.65 ± 0.06 U/ml) was significantly lower than that of controls (0.91 ± 0.04; P < 0.001), which suggests that factors other than IGF are responsible for the depressed SM activity.The conclusion that can be drawn from these findings is that the stunted growth associated with hypercortisolism cannot be attributed to an IGF deficiency. (J Clin Endocrinol Metab 54: 885, 1982) R ETARDED growth associated with either endogenous or exogenous hypercorticism is a well known phenomenon (1, 2) and constitutes one of the signs by which Cushing's syndrome may be diagnosed in young subjects.There have been conflicting reports concerning the secretion of GH in such cases, both normal and subnormal responses of plasma GH to provocative tests having been observed (3-10). Simultaneous treatment with glucocorticoids during GH therapy stunts growth if the doses are too high (11) and human GH administration has no effect on the retarded growth of children treated with large doses of glucocorticoid (6,12,13).A number of studies have demonstrated that glucocorticoids have a direct action on cartilage in addition to inhibiting the stimulatory ...

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Section: Discussionsupporting

confidence: 67%

“…A number of studies have demonstrated that glucocorticoids have a direct action on cartilage in addition to inhibiting the stimulatory effect of serum somatomedins (SMs) (14)(15)(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Serum Somatomedin/Insulin-Like Growth Factor (IGF) and IGF Carrier Levels in Patients with Cushing's Syndrome or Receiving Glucocorticoid Therapy*

Gourmelen

Girard

Binoux

1982

The Journal of Clinical Endocrinology & Metabolism

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“…Somatomedins stimulate mostly the synthesis of the protein core of the proteoglycans [21,22], but possibly also glycosaminoglycan synthesis [22,23]. Our data show that insulin is of importance also for the chain length of growth plate glycosaminoglycans.…”

Section: Diabetesmentioning

confidence: 86%

Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition

1983

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Insulin is an important growth factor in man and mammals. In the present investigation, we have studied the incorporation of (35S)-sulfate into growth plate proteoglycans in normal, diabetic, insulin-treated diabetic, and marasmic rats. We found that diabetes leads to an all-but-total stop in the synthesis of sulfated glycosaminoglycans. The glycosaminoglycan chains actually synthesized were shorter than in normal rats. The proteoglycan monomers were smaller and did not form large aggregates in vitro. Marasmic rats and insulin-treated diabetic rats were intermediate between normal and diabetic rats with respect to sulfate uptake by cartilage, incorporation of cartilage sulfate into glycosaminoglycans, and the chain length of glycosaminoglycans. We conclude that insulin and nutrition play important but different roles in the biosynthesis of growth plate proteoglycans and thus for the longitudinal growth of skeletal bones.

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“…The major form of IGF-II in the circulation contains 67 amino acids, but variant forms, at least one of which results from alternative splicing of the mRNA precursor [8], have also been identified. Functionally, the two IGFs have similar spectra of biological activities; in addition to their well-recognized mitogenic effects, these hormones also stimulate a wide variety of differen tiated functions including proteoglycan [10], myelin [11] and steroid hormone [12] synthesis in appropriate cell types. Moreover, the anabolic effects of both hormones appear to be mediated through the same cell surface receptor [13], termed the type I IGF receptor.…”

Section: Igfs In Human Serum: Characteristics and Circulating Formsmentioning

confidence: 99%

Insulin-Like Growth Factor Measurements in the Evaluation of Growth Hormone Secretion

Furlanetto

1990

Horm Res

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The measurement of circulating levels of the insulin-like growth factors (IGF-I and IGF-II) in the evaluation of GH secretion is discussed. GH is an important regulator of circulating IGF-I levels in humans. Circulating IGF-I levels are low in patients with GH deficiency, elevated in those with GH excess, and correlate well with physiologic changes in GH secretion. The levels also increase in response to administration of exogenous GH or GH-releasing hormone. However, IGF-I levels are age dependent and subject to regulation by other hormones and nutritional variables; these features complicate the interpretation of IGF-I levels in individual patients and limit the usefulness of these measurements, particularly for determining GH deficiency in young children. Circulating IGF-II levels are not GH dependent and, therefore, their measurement is of little clinical utility in assessing GH secretion.

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Alteration of Cartilage Glycosaminoglycan Protein Acceptor by Somatomedin and Cortisol

Cited by 26 publications

References 10 publications

Serum Somatomedin/Insulin-Like Growth Factor (IGF) and IGF Carrier Levels in Patients with Cushing's Syndrome or Receiving Glucocorticoid Therapy*

Serum Somatomedin/Insulin-Like Growth Factor (IGF) and IGF Carrier Levels in Patients with Cushing's Syndrome or Receiving Glucocorticoid Therapy*

Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition

Insulin-Like Growth Factor Measurements in the Evaluation of Growth Hormone Secretion

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