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Biomedical subjects

A Belgorosky

Publications and source records attributed to A Belgorosky.

48 records · Page 3Linked to original sources
PubMed1987

High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment.

We measured serum sex hormone-binding globulin (SHBG), total testosterone (T), non-SHBG-bound T, albumin-bound T, free T, and SHBG-bound T in 19 prepubertal boys with hypopituitarism. Serum SHBG decreased with age with a slope similar to that in 91 normal prepubertal boys at higher level, and therefore, it reached similar values at a later age. Serum SHBG was significantly higher in hypopituitary prepubertal boys [mean, 123 +/- 12 (+/- SE) nmol/L] than in normal prepubertal boys (76 +/- 4; P less than 0.001) despite the fact that their mean age was also higher (10.0 +/- 4 vs. 7.1 +/- 4.1 yr; P less than 0.001). In 4 boys with isolated hypogonadotropic hypogonadism (Kallman's syndrome), aged 15.6 +/- 1.5 yr, serum SHBG was 21 +/- 14 nmol/L, a value below the 95% confidence limit of the regression line in GH-deficient boys. The affinity constants of association of the SHBG-DHT complex were similar in hypopituitary and normal boys. Eleven of the 19 hypopituitary boys (mean chronological age, 8.3 +/- 2.5 yr; mean bone age, 4.1 +/- 2.1 yr) were treated with recombinant hGH (0.5 U/kg BW.week) for 1 yr. Their mean serum SHBG level before treatment was 154 +/- 14 nmol/L, and it decreased gradually to 106 +/- 5 nmol/L (P less than 0.01) after 12 months of treatment. The tendency toward normalization of serum SHBG during treatment suggested that GH deficiency was responsible for the high serum SHBG levels. Serum SHBG correlated negatively with age in both treated hypopituitary and normal boys, but the slope of the regression line was significantly steeper in treated hypopituitary boys (P less than 0.01). On the other hand, the mean serum non-SHBG-bound T level was 0.10 +/- 0.02 (+/- SE) nmol/L in hypopituitary boys, significantly lower than that in normal boys (0.21 +/- 0.02 nmol/L; P less than 0.02). Since serum total T concentrations were similar in the two groups, the higher serum SHBG concentration resulted in lower serum bioavailable T levels in the hypopituitary boys. These changes might explain the poor response to T treatment reported in GH-deficient patients. The lower serum non-SHBG-bound T concentrations in the GH-deficient boys suggest there may be delayed exposure of central nervous system structures to increased levels of sex hormones, which, in turn, may slow body maturation. This mechanism might play a role in the delay of puberty that occurs in patients with isolated GH deficiency.

Adolescent↗
PubMed1987

Variations in soluble and particulate ABP of rat testis during sexual development.

Androgen binding activity (ABP) was determined in two different fractions of developing rat testicular homogenates: in cytosol (cABP) and in a particulate fraction isolated by differential centrifugation (pABP). Homogenates were prepared under stabilization conditions by adding 350 nM testosterone to the homogenization buffer. cABP and pABP concentrations were maximal in 22- to 32-day-old animals, to decrease thereafter during sexual maturation. However, both cABP and pABP increased with age when results were expressed on a per organ basis. pABP could be solubilized under conditions in which it could retain its binding activity. It was then photoaffinity labeled and chromatographed on a Sephadex G 200 column using cytosolic epididymal ABP as a control. Similarities between cABP and pABP include not only the same androgen binding characteristics but also the same exclusion volume after Sephadex G 200 chromatography. Since pABP is only present in Sertoli cells, it might represent ABP before being secreted. Because of its intracellular localization, it could play a role in the compartmentalization of androgens within the testis.

Androgen-Binding Protein↗
PubMed1986

Progressive decrease in serum sex hormone-binding globulin from infancy to late prepuberty in boys.

Serum Sex hormone-binding globulin (SHBG) levels and affinity constant (Ka) of SHBG-dihydrotestosterone association were determined in 91 boys, aged 3 months to 15 yr, all at Tanner stage I of pubertal development. A gradual decrease in serum SHBG as a function of age was found in spite of unchanged serum testosterone levels. Ka values at different ages were not significantly different. Since steroids bound to SHBG are not transported into most tissues, particularly brain, a decrease in SHBG will have the effect of increasing tissue entrance of non-SHBG-bound sex hormones despite unchanged plasma concentrations. We speculate that the gradually increasing androgen and estrogen milieu of the brain created by this mechanism might be of physiological significance in triggering the onset of puberty.

Adolescent↗
PubMed1986

Photoaffinity labeling of extracellular and intracellular androgen binding proteins.

A method is described for the photoaffinity labeling of human and rabbit serum sex hormone binding globulin (SHBG) in ammonium sulphate precipitates utilizing 3H-delta 6-testosterone as affinity label. The precipitation step diminished albumin contamination and at the same time concentrated the binding globulin. Photolysis was conveniently carried out with an electronic flash. Unbound and non-covalently bound steroids were adsorbed by prolonged dextran-coated charcoal treatment. Sephadex G-200 gel filtration column chromatography showed a single peak of covalently bound radioactivity with the elution volume of SHBG. With some modifications, the method was applied to the affinity labeling of the prostate androgen receptor utilizing 3H-methyltrienolone (R 1881) as affinity label. The receptor was also precipitated from prostate cytosol with ammonium sulphate. After labeling, photolysis and heating at 50 degrees C, non covalently bound 3H-R 1881 was removed by dextran coated charcoal treatment. Sephadex G-25 microcolumn chromatography after heating showed a peak of radioactivity eluting with macromolecules if photolysis had been carried out, while it disappeared in the absence of previous photolysis. However, the photolabeled receptor had a sedimentation coefficient different from the non-irradiated receptor, suggesting that photolysis induced a change in the configuration of the complex.

Affinity Labels↗
PubMed1985

Sex hormone binding globulin response to testosterone. An androgen sensitivity test.

Adequate distinction between an abnormality in androgen secretion or in target cell response is important in the diagnosis and management of male pseudohermaphroditism. Hormone serum levels give reasonable information on steroid secretion, but there are no simple methods, in clinical practice, to evaluate target cell response to androgens. In this work, we have evaluated the validity of the acute decrease in serum (SHBG) after administration of hCG or exogenous testosterone, as an indicator of androgen sensitivity in prepubertal subjects. The results were expressed as percentage of basal values. In control subjects, after hCG, SHBG dropped below 85% of basal, mean 55 +/- 17, and, after exogenous testosterone, below 80%, mean 62.18 +/- 8.85. In 23 patients studied with the hCG test, 10 positive and 13 negative results were found, but most of the negative responses became positive after exogenous testosterone. Of 25 patients studied with the exogenous testosterone test, 19 positive and 6 negative results were found. Clinical analysis of these 6 patients with negative responses showed that 4 subjects had a confirmed androgen insensitivity syndrome, while clinical information was compatible with this diagnosis in the other 2 patients. Furthermore, in 4 additional patients with the androgen insensitivity syndrome, but with high basal serum testosterone, this test was also negative. It is concluded that determination of serum SHBG after hCG is not reliable as an androgen sensitivity test, but the detection of the decrease in serum SHBG after exogenous testosterone is a useful and simple test of androgen sensitivity.

Child↗
PubMed1983

Dynamics of SHBG response to testosterone. Implications upon the immediate biological effect of sex hormones.

The dynamics of the changes in serum concentrations of SHBG to variations in serum testosterone was studied in rabbits. Castration of male rabbits failed to produce changes in SHBG within 2 days but induced a significant increment 2 months later. Administration of 15 mg of testosterone to 5 male castrates produced a rapid decrease in SHBG concentrations from 215 +/- 121 nmol/l before, to 114 +/- 15, 6 h after (mean +/- SD), while 25 mg of the androgen barely changed SHBG levels in 5 females (from 81 +/- 26 to 72 +/- 22). Three of the males and the 5 females showed a tendency to recover basal levels at 24 and 48 h. Since SHBG is a major regulator of the availability of sex hormones to be transported into tissue cells for both biological action and degradation, the rapid changes in serum SHBG induced by testosterone might play a role in controlling its own biological effect. A decrease in SHBG will result in a more effective stimulation in androgen-responsive tissues, but it will also favor a faster interruption of the effect by increasing the rate of degradation. These androgen induced changes in SHBG are apparently different in male and females.

Animals↗
PubMed1983

Sex hormone binding globulin in arterial, and in peripheral, hepatic, renal and spermatic venous blood of children and adults.

Human sex hormone binding globulin (SHBG) was measured in arterial serum and in serum obtained from different venous territories. In 6 children, SHBG ranged from 44.4 +/- 4.8 (mean +/- SD) in arterial blood to 55.3 +/- 5.3 in the hepatic vein (P less than 0.01), while it did not change significantly in renal or peripheral tissue venous blood. In 6 male adults, no significant arteriovenous differences were found either in the peripheral tissues or in the splanchnic circulation. In the spermatic vein of 8 subjects, SHGB was significantly lower (17.1 +/- 5.7) than in the arterial blood (22.8 +/- 7.5), P less than 0.025. The arterio-venous difference found in the splanchnic circulation of children supports the hepatic origin of SHBG, and also suggests extra-hepatic clearance of the binding globulin. Testicular uptake of SHBG might be necessary to regulate delivery of androgens to Sertoli cells in the seminiferous tubules.

Adult↗
PubMed1982

Sex hormone-binding globulin response to human chorionic gonadotropin stimulation in children with cryptorchidism, anorchia, male pseudohermaphroditism, and micropenis.

Sex hormone-binding globulin serum concentrations (SHBG) were measured before and after a 5-day hCG stimulation test in 11 prepubertal boys with cryptorchidism, 6 with anorchia, 5 with male pseudohermaphroditism, and 5 with micropenis. Cryptorchid boys had decreased SHBG levels after hCG, by 55 +/- 17% (mean +/- SE) of the basal concentration. Patients with anorchia, who did not show an elevation in serum androgens, did not have decreased SHBG concentrations. Four of the 5 patients with male pseudohermaphroditism had an adequate elevation of serum androgens, did not have decreased SHBG concentrations. Four of the 5 patients with male pseudohermaphroditism had an adequate elevation of serum androgens after hCG, but in only 3 of them did SHBG decrease. None of the 5 patients with micropenis had decreased serum SHBG levels despite normal increments in serum androgens. The administration of a long-acting preparation of testosterone to sexually infantile subjects produce a similar decrease in the SHBG concentration. This change in SHBG concentration after hCG or testosterone in prepubertal boys could be used as a convenient test of biological response to androgens.

Adolescent↗
PubMed1981

Testicular function in prepubertal male pseudohermaphroditism.

Testicular function was evaluated in forty-one prepubertal patients with male pseudohermaphroditism by determining serum concentrations of progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone and dihydrotestosterone before and after stimulation with hCG and, in some instances, ACTH. Testosterone response to hCG was normal in all subjects. In one patient, a 4-year-old boy, a deficiency of 17,20-desmolase activity was diagnosed based on the coexistence of elevated levels of pregnenolone, 17-hydroxypregnenolone, progesterone and 17-hydroxyprogesterone and low levels of dehydroepiandrosterone and androstenedione. In three other patients enzymatic blocks were suspected but not confirmed. Congenital deficiency of enzymes necessary for testosterone biosynthesis is an uncommon aetiology of male pseudohermaphroditism.

Adolescent↗
PubMedDate not supplied

Evaluation of serum total thyroxine and triiodothyronine and their serum fractions in nonthyroidal illness secondary to congenital heart disease. Studies before and after surgery.

Serum thyroid hormones, serum thyroxine-binding proteins and serum thyroid hormone fractions have been measured in children with congenital heart disease before and after open cardiac surgery. Twenty prepubertal patients, mean (+/- SD) age 3.6 +/- 3.7 yr, were studied before, immediately after, and 24 and 48 h after surgery. A control group of 6 normal prepubertal children was also studied in basal conditions. Serum TSH was normal in all samples collected. Significantly low mean levels of serum TBG (261 +/- 57 vs 456 +/- 71 nmol/L in normals), serum TBPA (2692 +/- 1119 vs 5999 +/- 2226 nmol/L), serum TBG-bound T4, serum TBPA-bound T4, serum TT3, serum TBG-bound T3 and free T3 were found before cardiac surgery in the patients. While serum binding proteins did not change after surgery, significant decrements in serum TT4, serum TBG-bound T4, serum TT3, serum TBG-bound T3, serum albumin-bound T3 and free T3 were observed after surgery. Free T4 and albumin-bound T4 remained normal. Our study shows that many features of nonthyroidal illness were present in our patients before surgery. In this context, the stress of surgery induced further alterations in several parameters of thyroid metabolism. It is concluded that the changes occurring in this model of chronic, as well as acute, nonthyroidal illness reflect adaptative changes, rather than altered thyroid function, as shown by normal serum free T4, serum albumin-bound T4 and serum TSH.

Child↗
PubMedDate not supplied

Mutations of the steroid 21-hydroxylase gene in an Argentinian population of 36 patients with classical congenital adrenal hyperplasia.

In several studies carried out in USA and Europe, gene deletions, large gene conversions and six point mutations accounted for over 90% of the mutated alleles reported in classical congenital hyperplasia (CAH). In order to know the relative frequencies of mutations in a Latin-American population, the CYP21 active gene was analyzed in 42 patients with CAH belonging to 36 families attending two Argentinian clinics. The salt wasting form was diagnosed in 24 index cases and the simple virilized form in 12. When available, parents were also studied. DNA was extracted from peripheral blood leukocytes and specific PCR amplification of four different fragments of the CYP21 gene was carried out, followed by electrophoresis of the amplified product. The four fragments include segments of the gene containing the six most frequently reported abnormalities in classical CAH: IN2, EX3, R356W, cluster EX6 and I172N. Point mutations were studied by allelic specific oligonucleotide hybridization; Q318X was studied by digestion of the PCR product with PsT1 restriction enzyme and electrophoresis on 6% non-denaturing polyacrylamide gels. Deletions and macroconversions as well as confirmation of homozygote point mutations were studied by Southern blotting. Percentage distribution of abnormalities was as follows: deletion/macroconversion 18, IN2 18, I172N 15.3, Q318X 13.8, R356W 5.5, EX3 2.7, cluster EX6 0, not characterized 26.7. The complete genotype could be determined in 20 families while in 12 additional ones, the mutation was detected in one allele. Deletion/macroconversion, IN2, EX3 and Q318X were detected more frequently in salt wasting patients while I172N and R356W were found in simple virilized patients. However, genotype was not always concordant with phenotype. It is concluded that there are differences in the frequency of several gene mutations and in that of deletion/macroconversion between this Latin-American population and several reported American and European populations. In particular the percentage of deletion/macroconversion, IN2, EX3 and cluster EX6 was lower while I172N was higher in our Latin-American population. Furthermore the frequency of mutations not characterized was larger. This information is useful to delineate appropriate strategies for prenatal diagnosis in this particular population.

Adrenal Hyperplasia, Congenital↗