Showing papers in "Annales D Endocrinologie in 1986"

[Discovery, anatomical mapping and biosynthesis of various families of endogenous opioid peptides].

Abstract: The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe (-Met/-Leu at their amino-terminus. Three distinct families of these peptides (beta-endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). Met-enkephalin, Leu-enkephalin and the related heptapeptide Met-enkephalin-Arg6-Phe7 and octapeptide Met-enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structures of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. At the present time the main question concerns the physiological significance of such a great diversity of endogenous opioid peptides.

Indoles in the photoreceptor cells of the lamprey pineal complex.

Abstract: In the pineal complex of the brook lamprey, the hydroxyindole-0-methyltransferase (involved in the biosynthesis of 5-methoxyindoles) displays a daily rhythm of activity with a nocturnal peak, during a light/dark cycle and in constant darkness. Immunoreactive indoles were found in both varieties of photoreceptor cells (P1 and P2): serotonin and N-acetylserotonin-like substances in P2 and a melatonin-like compound in P1. It is suggested that P1 and P2 are involved in indole metabolism.

The pharmacology of various classes of cerebral opioid receptors

Abstract: The research on endogenous opioid is only a decade old but the considerable number and the variety of studies devoted to this subject suggest that these neuropeptides might play a pivotal role in various biological functions. The most abundant opioid peptides enkephalins are synthesized as large precursors. They bind to several classes of receptors as mu and delta types and are degraded by specific enzymes (aminopeptidase M, enkephalinase, dipeptidylaminopeptidase) belonging to the group of metallopeptidases. The analysis of the functions of the enkephalinergic system can now be investigated by using recently designed selective mu (DAGO, TRIMU 5), delta (DTLET, DEPDPE), kappa (U 50, 488) agonists or antagonists (ICI 174, 864 for the delta type) and kelatorphan a complete inhibitor of enkephalin metabolism. The former probes were obtained by a rational approach based on the conformational adaptability of the endogenous peptides while inhibitors of enkephalin degrading enzymes were designed by taking into account crystallographic data on metallopeptidases. mu and delta receptors present distinct distributions in the brain. Enkephalinase visualized by autoradiography seems to be closely associated with opioid receptors. Pain control could be insured in brain structures by mu receptor-stimulation whereas both mu and delta types might be involved at the level of the spinal cord. In both cases, a "physiological" analgesia is produced by kelatorphan.

Photoreceptors in the teleost pineal organ. Daily fluctuations of indole metabolism.

Abstract: The present study in the pineal organ of the pike reports the existence of day/night variations in the levels of three indoles, and in the activity of two enzymes involved in their metabolism. Present and previous data indicate that the cone-like (P) and modified (MP) photoreceptors of the pineal organ translate the photoperiodic information into nervous and indolic (in P), or into indolic (in MP) signals, displaying circadian variations. It is questioned whether these cells which are functional units of the circadian system, contain a circadian oscillator.

[Osteoarticular pathology, hypercalcemia and adrenal insufficiency. Analysis of 113 cases of adrenal insufficiency].

Abstract: Rheumatologic manifestations, ectopic calcification and hypercalcemia of adrenal insufficiency (IS) were evaluated by a prospective study (S1) of 20 patients with IS and a retrospective analysis of 93 cases of IS (S2). When routine investigations were conducted they revealed very frequent osteoarticular lesions (19 of 20 cases, S1). Painful manifestations (arthralgia, myalgia), variable with fluctuations in the IS affection were observed in both groups (S1, S2). Analysis of group S1 showed a high number of periarthritic attacks (9 of 20 cases), and a significantly higher incidence of tendinous calcifications (p less than 0.03) and of multiple tendinous calcification disease (MCTM) (p less than 0.05) in relation to 20 matched controls. This combined affection MCTM-IS has not been reported previously. Calcification could be due to glucocorticoid deficiency, the only common factor for all cases, and the frequent calcification of ear pinna (greater than 30% of cases in the 2 groups) could be related to the same deficiency. Finally, reported in the 81 case-reports were 18 episodes of hypercalcemia, emphasizing the unrecognized frequency of this disturbance whose determining role is unclear.

Role of endogenous opioid peptides in the regulation of pituitary secretions

Abstract: Identification of modulatory properties of morphine on certain hormonal secretions and that of opiate-receptor specific endogenous ligands has stimulated research in many fields, including role of opioid peptides in hypophysial secretion regulation. Availability of long-acting agonists and of antagonists of opioid peptides has provided data on their pharmacologic effects and possible role in hormonal physiology. The aim of the present report is to provide an update review of the influence of opioid peptides in hypophysial secretion regulation, while accepting that multiplicity of peptides and receptors does not allow formal conclusions to be drawn. At pharmacologic doses, opioid agonists stimulate prolactin and growth hormone secretion whereas that of LH and ACTH is inhibited. Secretion of TSH is little modified and that of ADH is stimulus-related. The opioid peptides are involved physiologically in the multifactorial regulation of gonadotropin secretion, other hypophysial secretions being mainly unaffected. Finally, "hypothalamic" amenorrhea appears to be the only pathologic model for which opioid peptides can be implicated. Finer analysis of physiologic role of endogenous opioid systems and their possible pathologic effects requires availability of selective agonists and notably antagonists.

hGH and molecular biology

Abstract: This review summarizes the progress recently made through the approaches provided by DNA recombinant technology in the knowledge of the human growth hormone (hGH) gene and of the molecular basis of hGH deficiencies. The growth hormone gene is part of a family of five structural genes located on the long arm of human chromosome 17, over a distance of 55 kilobases (kb), and oriented in the same transcriptional 5' to 3' direction in the order 5' hGH-N, hCS-L, hCS-A, hGH-V, and hCS-B 3'. The five genes contain five exons interrupted by four introns, and they display a high sequence homology. GH and CS genes show class differences on their 3' side, approximately 100 base pairs beyond the polyadenylation sites. Analysis of homology regions has permitted to define duplication units useful to trace the evolution process of the cluster. The hGH-N gene codes for the normal, pituitary, 22K human growth hormone. The hGH-V genes codes for a variant peptide that can be expressed in vitro in transgenomic systems, but that is not known to be expressed in vivo. The hCS-A and -B genes each code for human chorionic somatomammotropin. They specify the same mature hormone and are expressed at different levels in term placenta. The hCS-L gene appears to be an unexpressed pseudogene and has a single base substitution, located in a splicing site, that would preclude normal mRNA maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of heparin on the radioimmunological assay of ACTH

Abstract: Heparin traps plasma ACTH, promoting the formation of aggregates with apparent high molecular weight as shown by chromatography on Sephadex G 50 fine columns. The percentage of 125I-ACTH which appeared in the void volume of the column, increased linearly with the log. dose of heparin. Heparin at concentrations of up to 100 IU/ml does not impair ACTH adsorption on either silicic acid or Quso G 32 as well as further elution by acetic acid/acetone/water (I : 40 : 59; V/V) or HCl O.I N. Silicic acid traps selectively ACTH but not heparin. Heparin interferes with direct RIA-ACTH in the plasma by decreasing 125I-ACTH binding to the antibodies and modifying the slope of the standard curve. Unsuitable artefacts induced by heparin, as overestimation or underestimation of plasma ACTH levels by RIA, can be avoid by previous hormone extraction from heparinized plasmas. Such results emphasized the importance of the sample preparation in order to obtain consistent results.

[Treatment of cyclic attacks of acute intermittent porphyria with an LH-RH agonist administered by the intranasal route].

Abstract: A 31 year old woman suffering of acute intermittent porphyria (AIP) developed within 9 months 7 cyclical attacks occurring in a average of 5,2 days before menses. In order to inhibit ovulation, we experiment a long-acting agonist LH-RH (D-SER (TBU) 6-EA10 LH-RH--Buserelin) administered during 8 months by nasal spray. Menses did not occur during the test and the patient developed only 2 attacks. The initial ovarian stimulation phase lasted 15 days and was marked by the induction of an AIP attack after 3 days of treatment and occurrence of ovarian cysts. Our case suggests that LH-RH analogues may be useful in the prevention of cyclical attacks of porphyria.

[Current status of somatocrinin, or GRF, a hypothalamic growth hormone-secreting factor].

Abstract: UNLABELLED This short review on GRF is divided into two parts: laboratory findings: Current status of the knowledge on the primary structure of all the GRFs isolated from mammalian sources; structure activity relationships as obtained with synthetic fragments and analogs of GRF; the mechanisms of action of GRF in vitro and in vivo; the localization by techniques of hypothalamic GRF neurons. CLINICAL STUDIES A summary of past and current clinical studies with hGRF or fragments of hGRF establishing the dose range/effect in normal young adults; pharmacokinetics of hGRF; intravenous, sub-cutaneous and intranasal modes of administration; multi hours perfusions; the use of hGRF alone and in combination with other releasing factors as a diagnostic tool; early clinical results of stimulation of statural growth. Limited bibliography.

Renin secretion. Mechanism and effectors

Abstract: Renin secretion from juxtaglomerular cells of the kidney is controlled by several effector systems, such as renal perfusion pressure, renal nerve activity, salt load to the distal tubule and various humoral agents. The reactive behaviour of juxtaglomerular cells to these mechanisms is homologous to that of vascular smooth muscle cells of the kidney, i.e. manoeuvres inducing vasoconstriction inhibit renin secretion, whereas those inducing vasorelaxation stimulate renin secretion. This homology is partly explained by the fact that juxtaglomerular cells are modified smooth muscle cells. Intracellularly, an increase of cytosolic calcium has been identified as an inhibitory signal, whereas the major stimulatory signal appears to be cAMP (and the decrease of calcium). How intracellular calcium and cAMP are linked to the process of renin secretion, remains obscure.

From the renin gene to renin inhibitors

Abstract: The only known action of renin is the hydrolysis of angiotensinogen into angiotensin I. Renin is synthesized as an inactive precursor, preprorenin. The processing of prorenin into active renin occurs after the clivage of a profragment, just after a dibasic pair of amino-acids. The renin profragment hinders the active site by its binding to the rest of the molecule. Circulating inactive renin is prorenin because it is recognized by antibodies produced against various parts of the renin profragment. Renin, like other aspartyl proteases, hydrolyses its substrate in its active center where two aspartyl residues are involved in the catalytic mechanism. The strong species specificity of renin lies in its interaction with its substrate through subsites which can be modelized by computer graphics. There is much promise in the inhibition of the renin angiotensin system at the level of the renin-angiotensinogen reaction. The i.v. infusions of human renin antibodies in primates produces a decrease in blood pressure which is parallel to that observed during inhibition of the angiotensin I converting enzyme. The magnitude of the blood pressure decrease depends on the intensity of the sodium depletion. Potent and specific pepstatin derived inhibitors have been synthesized which are able to inhibit primate renin in vitro and in vivo with a long duration of action. Other transition state analogs inhibitors have been administered parenterally in humans and similar results have been obtained. The concept of the treatment of hypertension by an anti-renin drug is becoming more and more a reality. However, it remains to find an orally active and a non-toxic compound which will compare well with the present converting enzyme inhibitors.

[Characterization and modulation of anterior pituitary binding sites for rat corticotropin releasing factor (r-CRF)].

Abstract: Specific binding sites for rat CRF (r-CRF) have been characterized on rat anterior pituitary membranes. The binding of the radioiodinated analog of r-CRF (125I Tyr-r-CRF) was time, temperature, pH and protein dependent. No interaction was found with other neurohormones except with Arginine Vasopressin, but at supra physiological levels. Two classes of specific binding sites (high affinity and low affinity) for r-CRF were identified. Bilateral adrenalectomy provoked, since the 24th hour and up to 7 days, in addition of an increase of ACTH plasmatic levels, an abolition of the high affinity binding site; corticosterone treatment reversed these changes. This finding suggests that circulating glucocorticoids may control the anterior pituitary binding sites for CRF, either by a direct action on the anterior pituitary, or by a modulatory effect on hypothalamic CRF secretion.

[New data on the adrenal-post-pituitary system of cancer patients].

Abstract: A water loading test was performed in 10 patients with a cancer of the digestive tract without hyponatremia and in 10 controls. A lowering of the CfH2O was observed in the patients during the test, as well as an increase in the cortisol plasmatic rates, while aldosterone rates remained normal. To valid the hypothesis of a hypervasopressinic state in these patients, 15 cancerous patients and 12 controls had a plasmatic ADH dosage, which pointed indicated higher hormonal level in the first group.

Autoimmune polyendocrinopathies. Pathogenic hypotheses

Abstract: In most of the cases, once a given endocrine gland is involved, the corresponding specific autoantibody may be detected; for example, anti-islet cell antibodies are produced within the first few years, after onset of symptoms in insulin-dependent diabetes (DID). Accompanying autoantibodies are quite frequently found in the patient himself. In Schmidt's syndrome (thyroid and adrenal glands are involved and associated to IDD in 30% of the cases) thyroid microsomal antibodies are found in 38% of the cases, thyroglobulin antibodies in 11% of the cases, islet-cell antibodies in 7% of the cases and steroid cell antibodies in 17% of the cases. Associations are also possible in patient family members. Aberrant expression of HLA-DR molecules at the membrane of follicular thyroid cells (as of any other endocrine gland), following a viral aggression, could well account for the endocrinopathy combinations, but alternative mechanisms should be discussed.

[Hashimoto's thyroiditis with intra-thyroid production of a monoclonal antithyroglobulin autoantibody].

Abstract: A 46-year old man had an Hashimoto's thyroiditis. The disease was particular by the voluminous goiter, associated with pressure symptoms and by the presence of a monoclonal Ig.G Kappa. Because of a possibly associated lymphoma of the thyroid, a total thyroidectomy was performed. Post-operative course showed a rapid and total disappearance of monoclonal Ig.G and antithyroglobulin autoantibodies. There was no pathological feature of thyroid malignancy. We could show that the monoclonal Ig.G bore an antithyroglobulin activity and that this monoclonal antithyroglobulin autoantibody was produced with in the thyroid. This case demonstrate that a monoclonal proliferation can arise from autoreactive B lymphocytes infiltrating the thyroid during Hashimoto's thyroiditis. Such a mechanism could explain, in some cases, the well-known association between lymphomas of the thyroid and Hashimoto's thyroiditis.

Treatment of thyroid ophthalmopathies by external orbital radiotherapy

Abstract: From January, 1977, through December 1983, 62 patients with thyroid edematous ophthalmopathy were given external orbital radiotherapy according to S.S. Donaldson's technique: 5,5 MV photons produced by a linear accelerator were used to irradiate the muscular conus, with a total of 20 grays in 10 sessions over 2 weeks. Good results were obtained in 46 patients (77%). This simple therapy may be a first choice in recent ophthalmopathy.

Effect of LHRH on the synthesis and phosphorylation of proteins in gonadotropic cells

Abstract: Protein secretion by cultured pituitary cells from 14 day-old female rats was estimated using [35S]-methionine incorporation, electrophoresis and autoradiography. Stimulation by LHRH promoted biosynthesis and fast release of a protein of apparent molecular weight 87,000 daltons and pI 4.6. Gonadotrophs enriched by centrifugal elutriation were particularly rich in this polypeptide which was thus called GP-87 (Gonadotrope polypeptide). Cells were then cultured with [32P]-orthophosphate and proteins were analyzed. Our first results tend to show that GP-87 is phosphorylated, at least in the cells. We suggest that this specific protein, the secretion of which is correlated with LH release, participates to the response mechanisms of gonadotrope cells stimulated by LHRH.

[Estradiol-progesterone interaction in normal and pathological human breast cells].

Abstract: In most target tissues of the female genital tract, an adequate cell differentiation can be obtained with the successive and synergistic action of estradiol (E2) and progesterone (P), essentially because the progesterone receptor (PR) synthesis implicates the previous action of E2 via its E2 receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas the development of acini depends on P secretion. In other words, when E2 plus P are secreted by the ovaries in balanced proportions, the two hormones permit a complete and harmonious development of the mammary gland. The antiestrogenic activity of P is carried out through the decrease of ER resynthesis and stimulation of 17 beta-hydroxysteroid dehydrogenase enzyme activity, which transforms E2 into its less active metabolite estrone (E1) in the target cells. These biochemical events are well documented concerning the endometrium. They have also been observed in normal mammary cells in primary cultures as well as in breast fibroadenomas with high epithelial cellularity. Moreover, data from literature indicate that E2 could be both a direct and indirect factor of cell multiplication in cancerous cell lines. P as well as progestins have the opposite effect. Recent results from this laboratory indicate that E2 and P also have antagonistic effects on the cell multiplication of normal human mammary cells in primary culture. Therefore, the hypothesis that a lack of P during a long period of the female genital like could be a factor in the promotion of breast cancer must be considered.

[Ultrasensitive TSH : a new diagnostic approach to hyperthyroidism].

Abstract: The value of new ultrasensitive and rapid immunoradiometric assay of thyroid stimulating hormone (TSH) for the diagnosis of hyperthyroidism was assessed in 130 patients with suspected hyperthyroidism and in 330 controls. The diagnosis was established by the clinical evaluation, thyroid scintigraphy and serum concentrations of thyroid hormones. Using the ROC (Receiver Operating Characteristic) curve methodology which allows the optimization of sensitivity and specificity, the physician can choose the "Cut-off" value between hyperthyroidism and euthyroidism. Two points of the curve seem to be interesting : using the "cut-off" value of 0.1 mUI/l, sensitivity is 0.98 and specificity is 0.98 ; using the "cut-off" value of 0.3 mUI/l, sensitivity is 1.00 and specificity is 0.92. Using the association TSH and FT4 (Free Thyroxin), sensitivity is 0.94 and specificity is 0.99. Sixty four per cent of euthyroid patients with TSH under 0.3 mUI/l have one or several hot nodules and only two have no thyroid disease. A TRH (Thyrotrophin Releasing Hormone) test was carried out in 63 patients with suspected thyrotoxicosis : basal and TRH stimulated TSH levels were under 0.1 mUI/l. This immunoradiometric assay for TSH may simplify the approach to thyroid function testing in patients with suspected thyrotoxicosis : a basal TSH under 0.3 mUI/l is sufficient to confirm a clinical suspicion of thyrotoxicosis without TRH test within four hours. In a department devoted to testing thyroid function, this new method provides a great benefit in cost and work.

[Catecholamines in the cardiovascular expression of pheochromocytoma. II--Study of free urinary catecholamines in 14 pheochromocytomas. Classification of pheochromocytomas according to type of secretion].

Abstract: Studies were conducted in 14 patients with pheochromocytoma over a 3-year period. Circumstances of detection of these tumors varied greatly and were sometimes misleading, hypertension being an inconstant finding in the clinical history and was not always the predominant feature. Biologic exploration involved assay of excretion of free urinary noradrenaline (NA), adrenaline (AD) and dopamine (DA) using a HPLC technique as well as assay of total methoxy derivatives and urinary vanilmandelic acid. Validity of each assay in the diagnosis of pheochromocytoma could be evaluated and only the total free methoxy derivatives gave false negative results. Hormonal secretion of pheochromocytoma is often mixed, but sometimes predominant or exclusive for a single catecholamine. Relative increases of the different catecholamines, evaluated from the ratios DA/NA and DA/NA + AD, are an important factor since a relation exists between blood pressure induced symptomatology and equilibrium between hypotensive hormone (DA) and pressor amines (NA + AD); 3 types of pheochromocytoma can be described: NA-induced with paroxysmal or permanent hypertension but without typical metabolic and cardiac disorders, and with a very reduced DA/NA + AD ratio during hypertensive crises; AD-induced without permanent hypertension but with a mainly orthostatic hypotension and episodes of cardiovascular collapse following hypertensive attacks and with an AD/NA ratio greater than 1; finally the DA-induced lesion in which hypertension is never associated and manifestations are misleading and atypical with an elevated DA/NA + AD ratio.

Phosphorylation of cytoplasmic proteins related to the multihormonal regulation of anterior pituitary cells

Abstract: Thyrotropin releasing hormone (TRH) stimulates the synthesis and release of prolactin in mammotropic cells of the anterior pituitary and in GH4C1 cells. TRH simultaneously enhances the phosphorylation of a small number of proteins revealed in GH4C1 cells by two dimensional gel electrophoresis. The same phosphoproteins could be detected in normal rat pituitary cells in primary culture and were phosphorylated with the same pharmacology as in GH4C1 cells. Moreover, these proteins may also be related to hormonal regulations of the other cell types of the anterior pituitary.

[Innocuousness of the limited reuse of injection materials by insulin-dependent diabetics].

Abstract: A survey was conducted in 120 insulin-dependent diabetics to determine their routine daily procedure for insulin injection and the possible reuse of the material employed. Aseptic precautions were usually sufficient, half of the diabetic patients (51.6%) conforming with the overall rules for hygiene generally recommended. Spontaneous reuse of injection material was rare (10/120), and local incidents as a result of reuse infrequent: pain from the 3rd injection in 2 patients and an abdominal abscess in a third case due to total lack of asepsis rules. Insulin injections in 37 insulin-dependent diabetics admitted to hospital care were administered throughout their stay by means of plastic syringes and needles used 3 times consecutively. The mean number of needles-syringes used per diabetic was 7.3, representing a total of 813 injections. Infectious sequelae were not observed and minor local incidents (pain, pruritus) were rare and unrelated to the reuse of equipment. Limited reuse, under satisfactory conditions of asepsis, of material termed for "once only use" appears to be free from risk particularly with respect to infection. Generalization of this practice will provide substantial economy in the treatment of diabetes.

Influence of gonadotropins on inhibin secretion

Abstract: Inhibin is produced by Sertoli cells in the male and by granulosa cells in the female. Follicular-stimulating hormone acts directly to stimulate production whereas luteinizing hormone exerts an indirect effect by stimulating production of androgens which themselves activate synthesis and release of inhibin. Prolactin has no effect on inhibin. These interpretations, derived from numerous in vivo and in vitro studies, explain why inhibin is not secreted in the hypophysectomized animal. Interruption of spermatogenesis by ligature of deferens canals, by experimental cryptorchidism in the rat, and in human primary azoospermias, provokes a reduction in production of inhibin and an increased secretion of FSH. The second must be the consequence of the first. Restoration of normal spermatogenesis results in normal production of inhibin. Biochemical mechanisms linking spermatogenesis and inhibin production are still unknown.

[Detection of thyroid cancer : utopia or reality? Or the value of thallium 201 in thyroid pathology].

Abstract: Faced with a diagnosis of cold thyroid nodule as evidenced by routine scintigraphy, the clinician has to determine whether this nodule is malignant or not. This is a serious problem since, according to literature, 7-20% of cold thyroid nodules are malignant. In 1982 some Japanese authors demonstrated the possibility of using 201 T1 in diagnosing thyroid tumors. This study refers to 120 patients who underwent an operation for thyroid disorders characterized by the presence of one or several cold nodules (as evaluated with conventional scintigraphy) and enables a comparison between a thorough evaluation of the thyroidal status and the 201 T1 scintigrams. These were obtained with a gamma-camera using a pinhole collimator. If a cold nodule is positive with 201 T1, surgery is incontestably indicated, as such a finding correlates with the existence of a thyroid tumor (benign follicular adenoma or carcinoma) in 89.5% of the observed cases. In the cancer group the sensibility of the Thallium test is of 85% and its specificity 80%. We may assert that there is a very low risk of Thallium negative (old) nodules being malignant. The pre-operative 201 T1 scintigraphy is easy to perform in any Nuclear Medicine department. Nowadays, the combination of aspiration cytology and 201 T1 scintigraphy should make it possible to make and accurate diagnosis in the vast majority of differentiated and undifferentiated thyroid cancers.

[The human renin-secreting cell. A morphological study].

Abstract: The availability of specific antisera to renin and the techniques of immunocytochemistry have facilitated the microscope study of renin-secreting cells. These techniques have been used in recent studies in the developing kidney as well as in both normal and pathological adult kidney. This work has clarified the close relationship between myoepithelioid cell and the blood vessel. The use of ultrastructural immunocytochemistry has led to new insights into the intracellular processing, storage and secretion of renin. These recent morphological studies are reviewed with the emphasis on the human renin-secreting cell within the kidney.

[Somatomedins. Structure, physiology and clinical data].

Abstract: For an adequate interpretation of the significance of somatomedin levels in clinical conditions, a number of factors should be considered which may have an influence on the result. First of all, the heterogeneity of the somatomedins, both in their complexed form and after dissociation, should be considered. These forms have an unequal degree of cross-reactivity in different assay systems, while only the function of SM-C/IGF-I and, to a minor degree, of IGF-II have been established. Both are mitogenic and IGF-II has more insulin-like effects than does SM-C/IGF-I. Only the latter has been shown to increase length in dwarf mice. Somatomedins are produced in many tissues. This has led to the concept of autocrine or paracrine functions. The levels of SM-C/IGF-I increase with age, and there is a large increase during puberty, particularly when measured in the radioimmunoassay. In addition its level is influenced by growth hormone, to a minor degree by thyroid hormones, prolactin and perhaps by HCS and insulin. Finally, the nutritional and metabolic state of the patient is important: low values have been found in malnutrition, poorly regulated diabetes mellitus and insufficiency of the liver. Measuring somatomedins may be helpful for diagnosis and evaluation of the therapy of certain disorders, but the complexity of the regulation of their blood levels needs caution in the interpretation of results.