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Biomedical subjects

M Donnadieu

Publications and source records attributed to M Donnadieu.

At least 19 recordsLinked to original sources
PubMed1991

The binding of different biosynthetic and extracted human growth hormones to the growth hormone-binding protein of human serum: a comparative study.

This study of the human growth hormone binding protein (GHBP) was undertaken using several samples of hGH, extractive or recombinant, from different origins. They were labelled in identical conditions and assayed by gel chromatography after incubation with three human sera having different levels of binding activity. For each serum the binding activities of the five recombinant hormones were very close and significantly higher (P less than 0.005) then the binding activities of the 2 extractive hormones. A radioactive peak which appeared in the zone of high molecular weights was more important with extractive than with recombinant hormones (P less than 0.01). This peak increased with the ageing of the tracer and appeared even when the tracer was incubated in the absence of serum. Thus, it is for its main part not related to another binding protein but, more likely, to a polymerization of the hormone. These data point out the importance of accurate technical conditions to have a reproducible assay for GHBP and to interpret the results in studies of growth disturbances.

Adult↗
PubMed1991

Effect of retinoic acid on platelet-derived growth factor (PDGF) bioactivity and type-B PDGF receptors in normal and psoriatic human fibroblasts.

Psoriasis is a common skin disease in which retinoids have beneficial effects. It offers a model for the study of benign hyperproliferation with abnormal differentiation. The dermis has a prominent role in the appearance of epidermal lesions. It is therefore of interest to study the factors that modulate dermal cell proliferation. In this study, the role of retinoids in modulating platelet-derived growth factor (PDGF) bioactivity was studied in normal (six subjects) and psoriatic fibroblasts from involved and uninvolved tissues (six patients). Retinoic acid treatment (for 4 d at 10(-6) M) of psoriatic fibroblasts significantly increased the chemotactic effect of PDGF in these cells (p less than 0.01 and p less than 0.05, respectively, in involved and uninvolved skin at 20 ng/ml of platelet-derived growth factor as measured in a modified Boyden Chamber Assay). In the same way, retinoic acid treatment of psoriatic fibroblasts increased the mitogenicity of platelet-derived growth factor in these cells. Retinoic acid treatment has no significant effect on the mitogenic and chemotactic activity of PDGF in normal fibroblasts. The binding of the homodimer BB PDGF to its type-B receptor, which mediates the mitogenic and chemotactic effect of PDGF, was not modified by retinoic acid treatment either in psoriatic and/or normal fibroblasts. These results suggest that retinoic acid may modulate the PDGF bioactivity in psoriatic fibroblasts not by affecting the binding of this ligand to these cells but by influencing a post-receptor event.

Adult↗
PubMed1991

[Laron type dwarfism. Study of GH binding protein in 3 cases].

Laron's type dwarfism (LTD) has clinical features very close to those of congenital isolated growth hormone (GH) deficiency, contrasting with high plasma levels of GH and a complete lack of growth improvement during treatment trials with exogenous GH. Three new cases are presented here. The plasma GH-binding protein (GHBP), which has been recently isolated and identified as similar to the extracellular part of the liver-cells receptor to GH, is lacking in two of the three patients and subnormal in their heterozygous parents, these data suggesting a defect of the GH receptor or of its extracellular part. In contrast, the third patient and her parents had normal plasma levels of GHBP, suggesting that the clinically and biologically obvious lack of receptivity to GH is either at the post-receptor level or limited to the intracellular part of the receptor. These data contribute to demonstrate that there are at least two different genetic defects leading to clinical LTD.

Carrier Proteins↗
PubMed1990

Growth hormone (GH) and GH-releasing hormone response to ACTH 1-17 at different times of day. Evidence of a circadian stage dependence.

The effect of injection of ACTH 1-17 on the secretion of GH has been examined at three different circadian stages (07, 14 and 21 h) in the winter. Each week for six consecutive weeks the subjects were investigated before and after I.M. injection either of saline (controls) or 100 micrograms ACTH 1-17. Each subject was his own control. The peak plasma concentration of GH was always found 40 min after the injection. The larger absolute increase and the greater AUC curve were seen following the injections at 14.00 h and 21.00 h. The findings could not be attributed to an effect on GH-RH, since secretion of it remained unchanged during the test.

Adolescent↗
PubMed1990

Increase of IGF I binding to erythrocyte receptors during the TRH-test: correlation between IGF I binding and thyroid hormone values.

The effects of TRH on insulin-like growth factor I receptors were investigated on erythrocytes from 7 GH-deficient children having plasma GH levels less than 10 ng/ml during two provocation tests. Intravenous injection of synthetic TRH (0.2 mg/m2) was followed by a marked increase of IGF I binding on erythrocytes, from 3.9% +/- 0.3% to 5.9% +/- 0.3% (P less than 0.005) after 1 hour and 7.3% +/- 0.4% (P less than 0.005) after 2 hours. The IGF I binding variations were due to an increase in both the receptor affinity and the number of sites. The levels of plasma GH, IGF I, T3, T4, free T4, TSH and prolactin having been determined during the TRH test at 0, 1 hour, and 2 hours after the injection, the increase in the IGF I binding to erythrocytes at the same time correlated with the rise of thyroid hormones: triiodothyronine T3 (P less than 0.001) and thyroxine T4 (P less than 0.005) and not with the level of the other hormones. These findings suggest that thyroid hormones play a role in the regulation of insulin-like growth factor I receptors.

Child↗
PubMed1990

High-affinity serum growth-hormone-binding protein, absent in Laron-type dwarfism, is diminished in heterozygous parents.

Human serum high-affinity growth-hormone-binding protein (GHBP), as determined by incubation with 125I-GH followed by chromatography on AcA 44 gel minicolumns, is lacking in patients with Laron-type dwarfism (LTD). We found that the specific binding of 125I-GH to high-affinity GHBP in normal human serum (m +/- SD) was 11.5 +/- 1.8% in 10 children 2-3 years old, 15.3 +/- 2.2% in 10 children 5-8 years old, and 19.3 +/- 2.9% in 15 adults 20-40 years old. It was 0.3% in a 2-year-old child with LTD, and 10.6 +/- 11.3% in his parents. It was 0.1% in another child with LTD, 7 years old, and 14.4 and 14.8% in his parents. The mean value in the heterozygous parents (12.8 +/- 2.1%) was significantly lower (p less than 0.001) than control values. A void volume peak (VVP) of radioactivity, corresponding to the so-called low-affinity GHBP which eluted at the void volume in chromatographs of normal sera remained unchanged with sera of patients with LTD or of their parents and appeared even after incubations of the tracer without serum. This study (1) shows that high-affinity GHBP is diminished in heterozygotes with LTD; (2) confirms that high-affinity GHBP and VVP are independently regulated, and (3) suggests that a part of the VVP may not be related to GH binding to some serum components.

Adult↗
PubMed1990

[Laron-type dwarfism: heterogeneity of the biochemical abnormality in 3 children and their parents].

The authors report three cases of Laron-type dwarfism (LTD) having clinical features similar to those of congenital growth hormone (GH) deficiency, but with high levels of plasma GH and a lack of effect of exogenous GH on their growth. The main plasma growth hormone binding protein (GHBP), recently identified and considered as being identical to the extracellular part of the cell receptor to GH, was absent in two of the three patients, and lower than normal in their parents, suggesting a defect of the cell GH receptor. The third patient and his parents had a normal level of GHBP, suggesting a defect limited to the intracellular domain of the receptor or lying beyond the receptor. The conclusion is that there are two different biochemical abnormalities corresponding to LTD.

Adult↗
PubMed1989

A cAMP binding abnormality in psoriasis.

In 34 psoriatic patients with various cutaneous manifestations (psoriasis vulgaris, erythroderma psoriaticum, guttate psoriasis), the ability of the RI regulatory subunit of cAMP-dependent protein kinase (PKA) to bind a cAMP analogue (8-azido [32P] cAMP) in erythrocyte membranes was significantly lower than that in 19 normal subjects (mean [SEM] 565 [35] vs 930 [35] fmol/mg protein). This enzyme defect was not found in patients with other forms of dermatitis that can be confused with psoriasis or with other inflammatory diseases. There was a significant negative correlation between the severity of the disease as expressed by the psoriatic area and severity index score and the binding of the cAMP analogue to PKA. A long-term study showed that oral retinoid treatment of psoriatic patients resulted in a correction of the binding defect. Unaffected members of psoriatic families had significantly lower than normal binding of cAMP to PKA (773 [60] fmol/mg protein). This study shows for the first time that in psoriasis a biochemical defect expressed in erythrocytes correlates with the severity of the disease as well as its clinical evolution. These results will be useful in clinical management of psoriatic disease for the choice and follow-up of retinoid therapy.

Administration, Oral↗
PubMed1989

Effect of human chorionic gonadotropin on growth velocity and biological growth parameters in adolescents with thalassaemia major.

The effect of long-term human chorionic gonadotropin (HCG) therapy on the linear growth and biological growth parameters was studied in six thalassaemic boys aged 14.5-15.5 years old with hypogonadotropic hypogonadism. A significant (P less than 0.001) increase in growth velocity (from 3.3 +/- 0.3 to 7.6 +/- 0.6 cm/year) was found after 6-12 months of therapy, without acceleration of bone age. A striking improvement in pubertal development was observed. The treatment significantly increased growth hormone (GH) response to L-dopa administration (P less than 0.025) as well as sleep GH secretion (P less than 0.025). Serum growth factors, evaluated as thymidine activity during deep sleep, increased (P less than 0.001), but somatomedin C (Sm-C) levels did not. Prior to treatment, baseline and peak values of plasma growth hormone releasing hormone (GH-RH) following L-dopa were low. After HCG therapy, GH-RH response to L-dopa increased significantly (from 9.2 +/- 5.6 to 20.2 +/- 6.2 pg/ml; P less than 0.05), but remained (P less than 0.001) lower than in normal prepubertal children. This study suggests that in thalassaemia major an impaired GH-RH release can be observed, in addition to the described alteration in Sm-C generation.

Adolescent↗
PubMed1989

[Neurohormones coming from the normal and tumoral human anterior pituitary. Secretion and regulation in vitro].

Several neuropeptides, classically associated with the hypothalamus have been found in the anterior pituitary and their local synthesis has been hypothesized. Using normal and tumoral human pituitaries we found in the tissue itself different neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries while only stimulatory neurohormones like TRH and GHRH were found in tumoral tissue implying an imbalance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Fragments from normal pituitaries and dispersed cells from GH, PRL and nonsecreting adenomas, were perifused for 4 hours in a Krebs-Ringer medium collected every 2 min and GH, PRL, TRH, GHRH and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L DA, TRH or SRIH. Neuropeptides and DA were characterized by HPLC. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. There was an in situ regulation between SRIH and GH as their secretion profile was negatively correlated, GH secretion decreasing while SRIH secretion was increasing. Moreover the release of TRH was stimulated 5 to 20 folds by DA, while PRL decreased at the same time. Pulses of TRH and SRIH had differential effects on GHRH and SRIH release according to the nature of the tissue as TRH stimulated SRIH release from normal pituitary while it inhibited SRIH release from adenoma. These results indicate that anterior pituitary cells can release neuropeptides which are probably endogenously synthesized and have a local regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1988

Insulin-like growth factor I receptors on human erythrocytes from normal children: relationship with age.

The binding of insulin-like growth factor I (IGF I) on red blood cells has been studied in 13 children aged 8 months to 11 years and in 10 adults. The Scatchard analysis showed a curvilinear regression. In adults, the specific binding was 4.1% of the tracer, the mean number of high affinity receptor sites per cell (Ro1) being 0.88 (K1 = 10.74 nM-1) and the mean number of low affinity receptors sites (Ro2) per cell being 7.14 (K2 = 0.37 nM-1). In children the specific binding ranged from 3 to 6.5%. Ro1 ranged from 0.40 to 3.13 (K1 from 3.48 to 13.61 nM-1). Ro2 ranged from 2.88 to 17.25 (K2 from 0.03 to 0.65 nM-1). The most striking fact was the close positive correlation between the specific binding and the age of children (r = 0.914, P less than 0.001). These data suggest that the high growth velocity of young children, concomitant with the low plasma levels of IGF I which are physiological during infancy and early childhood, does not result from an increased binding of IGF I to cell receptors.

Aging↗
PubMed1988

[In vitro secretion of somatostatin (SRIH) by human adenomatous somatotropic cells. Relation with somatotropic hormone (GH) release and modulation by thyroliberin (TRH)].

SRIH and GH secretions by GH-secreting adenomatous human pituitary cells were analyzed in vitro in a perifusion system. Of the 13 adenomas studied, 7 secreted SRIH, in variable amounts (50 to 700 pg/ml/2 min., corresponding to 600 10,700 pg for the total experiment. SRIH secretion increased during the perifusion, the highest levels being observed at the end of the perifusion. GH secretion also varied from one adenoma to the other (6 to 500 ng/ml). In most cases, the secretion profiles were negatively correlated, GH secretion decreasing while SRIH secretion was increasing. In the presence of 10(-7) M TRH, GH secretion increased while that of SRIH decreased. The hypothesis of a paracrine and/or an autocrine role for SRIH as well as its possible in situ synthesis are discussed.

Adenoma↗
PubMed1986

Plasma growth hormone releasing factor levels in children: physiological and pharmacologically induced variations.

Plasma growth hormone releasing factor (GHRH) was measured by RIA in the plasma of 41 children with constitutionally short stature. Basal plasma GHRH was 51 +/- 10 pg/ml. L-Dopa induced a 2-fold increase in circulating GHRH 30-45 min before the elevation of GH. A positive correlation (p less than 0.005) was found between the peak of GH and GHRH during the dopaminergic stimulus. On the opposite, the secretion of GH induced by amino acids or clonidine is not preceded by an elevation of plasma GHRH. When a release of GH appeared after the insertion of the venous catheter alone, probably due to the stress, it was preceded by a rise of plasma GHRH. In four sleeping adolescents during the night no relationship was found between the peaks of plasma GHRH and the peaks of GH secretion. These results suggest that the various stimulations of GH secretion used for investigations of a short stature do not act in the same way at the hypothalamo-pituitary level.

Amino Acids↗
PubMed1986

Relationship of plasma growth hormone-releasing hormone levels to pubertal changes.

Basal plasma GH-releasing hormone (GHRH) concentrations were measured by RIA in 180 normal subjects (93 boys and 87 girls between the ages of 8 and 18 yr). Every subject was in good health and between -2 and +2 SD for height. Fourteen boys with delayed puberty also were studied. Plasma GHRH concentrations were higher during puberty than before it. At midpuberty, the mean GHRH levels in girls was 159.1 +/- 28.5 (+/- SEM) pg/ml, approximately 5-fold higher than the level in prepubertal girls (30.3 +/- 4.3 pg/ml). The mean plasma GHRH in midpubertal boys (101.4 +/- 11.5 pg/ml) was approximately 2-fold higher than the level in prepubertal boys (48.1 +/- 5.2 pg/ml). The GHRH levels in boys with delayed puberty more closely resembled those in boys at a similar pubertal stage than those in boys of similar chronological age. The dramatic rise in plasma GHRH levels during puberty suggests a role for this peptide in the adolescent growth spurt. Moreover, these data indicate that GHRH levels during adolescence may be a marker of the patient's pubertal development.

Adolescent↗
PubMed1986

Negative correlation between peripheral plasma somatostatin levels and GH responses to GH-RH stimulation tests in children.

On forty-six fasting and resting children, aged 5-17 years, with short stature (below -2 SD) a growth hormone releasing hormone (GH-RH) stimulation test (2 micrograms/kg iv bolus, Sanofi) was performed. Twenty-two children were prepubertal, of which, 13 had a constitutional short stature (CSS), nine an idiopathic growth hormone deficiency (IGHD). Twenty-four subjects were pubertal, at the stage II or III of Tanner. Among them, six had a constitutional short stature (CSS) and 18 an idiopathic delayed puberty (IDP). Blood samples were taken for determination of plasma somatostatin-like immunoreactivity (SLI) in chilled test tubes containing EDTA + aprotinin. Plasma SLI levels were measured after extraction and concentration on C18 Sep Pack columns by radioimmunoassay using an antibody against 1-14 somatostatin. The sensitivity of this assay is around 3 pg/ml. After GH-RH stimulation the peak of GH (mean +/- SEM) was in prepubertal subjects: 25.3 +/- 9.1 micrograms/l in CSS, and 18.6 +/- 10.3 micrograms/l in IGHD. In pubertal subjects GH peaks were 17.6 +/- 8.4 micrograms/l in CSS and 15.6 +/- 3.8 micrograms/l in children with IDP. No significant differences was found between basal plasma SLI levels in the four groups of subjects, being respectively (mean +/- SEM) 11.9 +/- 1.8 pg/ml in prepubertal subjects with CSS, 9.6 +/- 2.6 pg/ml in IGHD, 7.6 +/- 1.7 pg/ml in pubertal children with CSS and 6.6 +/- 1.5 pg/ml in children with IDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1979

Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins.

In order to characterize more accurately the relationship between immunoreactive beta-MSH ("BETA-MSH") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of "beta-MSH" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human beta-MSH. When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human beta-MSH (hbeta-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma "beta-MSH" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000-10 000; no "beta-MSH" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of "beta-MSH" with a main peak in the molecular weight range of 6000-10 000. In our radioimmunoassay the culture medium and purified hbeta-LPH gave parallel displacement curves for [125I]hbeta-MSH. It is suggested that hbeta-LPH or a closely related substance is the main material responsible for "beta-MSH" immunoactivity.

Addison Disease↗
PubMed1978

Variations of serum testosterone estradiol binding globulin (TeBG) binding capacity in infants during the first year of life.

Serum TeBG binding capacity was measured in 8 cord blood samples, and in peripheral venous blood from 39 male and 31 female infants aged from 1 day to 1 year. In cord blood, TeBG binding capacities were low (1.27 +/- 0.3 microgram/100 ml) with no sex difference. In male infants, TeBG binding capacities increased progressively from birth to 3 months, before decreasing to reach the normal prepubertal level at 6 months. Individual values ranged between 1.16 and 14.5 microgram/100 ml and were significantly correlated with plasma testosterone (r = 0.671, 95% confidence limits 0.440 to 0.818, p less than 0.005) and estradiol (r = 0.734, 95% confidence limits 0.121 to 0.942, p less than 0.01) levels. In female infants, individual values ranged between 1.17 and 14.5 microgram/100 ml, without correlation with age or plasma estradiol level. In male infants the data suggest a positive control ot TeGB binding capacity by estrogens, the negative effect of testosterone being delayed until after the 3rd month of age. In girls, the lack of correlation between TeBG and estradiol can probably be explained by rapid variations of plasma estradiol levels.

Age Factors↗