PubMed Health⌕ Search

Biomedical subjects

A Belgorosky

Publications and source records attributed to A Belgorosky.

18 recordsLinked to original sources
PubMed1992

High serum sex hormone-binding globulin (SHBG) in premature thelarche.

OBJECTIVE: We determined serum sex hormone-binding globulin (SHBG), serum dehydroepiandrosterone sulphate, serum oestradiol and serum testosterone and its fractions in girls with premature thelarche. DESIGN: Blood was drawn from girls with recently diagnosed (3-12 weeks) premature thelarche. Serum was kept frozen for at least one year before hormonal determination to exclude precocious puberty by clinical evaluation. PATIENTS: Seventeen girls with premature thelarche aged 0.83-7.16 years were studied, and compared with a group of 22 normal prepubertal girls. MEASUREMENTS: SHBG was measured by saturation analysis and serum dehydroepiandrosterone sulphate, serum total oestradiol and serum total testosterone were determined by radioimmunoassay. Non-SHBG-bound testosterone and free testosterone were calculated from an equation derived from the law of mass action. RESULTS: Median serum SHBG in premature thelarche was 137 nmol/l (range 64-221), significantly higher than in normal controls, 93.7 (32-172) (P < 0.05) non-parametric test of medians. Serum SHBG decreased significantly with age in controls but not in premature thelarche. No difference was found in serum dehydroepiandrosterone sulphate. Median serum total testosterone (0.34 nmol/l, 0.17-0.97), median serum non-SHBG-bound testosterone (0.04 nmol/l, 0.02-0.10) and median free testosterone (2.2 pmol/l, 1.0-4.5) were significantly lower in premature thelarche than in control (P < 0.001). CONCLUSIONS: Serum SHBG is high and bioavailable T is low in girls with premature thelarche. This might alter the oestrogen/androgen ratio in the breast.

Breast↗
PubMed1992

Endocrine disorders in 66 suprasellar and pineal tumors of patients with prepubertal and pubertal ages.

Tumor oncotypes, initial symptoms and endocrine disturbances before and/or 1 month after surgery were studied in 66 patients with prepubertal and pubertal ages having suprasellar or pineal intracranial tumors. Neoplasms found in patients of prepubertal age were: 15 craniopharyngiomas (CRA), 24 neuroepithelial-cell-derived tumors (NEC), 5 germ cell tumors (GERM) and 4 other lesions (OTHER). In patients of pubertal age, there were 7 CRA, 7 pituitary tumors (PIT), 2 NEC, 1 GERM and 1 OTHER. Approximately 90% of patients had visual abnormalities as one of the initial signs and symptoms, while 59% had increased intracranial pressure. Short stature was observed in only 10% of patients. Before surgery, somatotropic function was found to be deficient (by 2 pharmacological tests) in 90-100% of patients with CRA, PIT or GERM and in 40% of patients with NEC. Overt hypothyroidism was found in 5-25% of CRA, NEC or GERM but in 40% of PIT. Abnormal TSH responses to TRH were observed in 64% of CRA and in 29% of NEC. Low basal serum cortisol was found in 21 or 6% of patients with CRA or NEC, but in 100 or 60% of patients with PIT or GERM, respectively. Diabetes insipidus was diagnosed in 13.6% of all patients. Surgery produced few additional disturbances in endocrine function, except for the incidence of diabetes insipidus which was doubled. Gonadotropic deficiency was found in most patients of pubertal age with CRA and PIT. They were readily differentiated by the high prolactin or growth hormone (GH) levels of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Primary culture of prepubertal human testicular cells isolated from testes collected at necropsy.

The aim of the present work was to develop a method for maintaining prepubertal human testicular cells in culture. Seven pairs of testes of boys who died of causes unrelated to endocrine or metabolic diseases were obtained at necropsy. Histology of the testes was normal. Testes were digested with collagenase and dispersed cells were seeded in multi-well dishes in the presence of 5% bovine fetal serum. After the first day, cells were cultured for five days in serum-free medium in the presence or absence of 918 pmol/l insulin. At the end of culture, microscopic examination showed healthy looking cells with characteristics compatible with pre-Sertoli cells; peritubular cells were identified by immunocytochemistry. In the presence of insulin, cells were able to secrete either testosterone or estradiol into the medium, as well as to reveal aromatase activity. In order to study the effect of the time elapsed between death and beginning of cultures, steroidogenic activity was related to this post mortem time. It was found that, in the presence of insulin, cells obtained from testes with less than 24 h of post mortem time secreted testosterone (64 +/- 7.2 pmol/10(6) cells.24 h, mean +/- SD) while cells obtained from testes with more than 24 h of post mortem time did not secrete testosterone. With long post mortem times, aromatase activity under insulin increased from non-detectable to 35 pmol/10(6) cells.24 h. Time course studies showed that cells with capacity to secrete testosterone increase this secretion gradually up to day 10 of culture, while those with detectable aromatase activity showed increments in this activity during the first week of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aromatase↗
PubMed1991

Serum sex hormone-binding globulin and serum nonsex hormone-binding globulin-bound testosterone fractions in prepubertal boys with chronic renal failure.

We had previously reported that serum sex hormone binding-globulin (SHBG) decreases and serum non-SHBG-bound testosterone (T) and free T increase significantly from infancy to late prepuberty in normal prepubertal children of both sexes. We had also shown an age-related delay in these changes in hypopituitary boys, which was reversed by GH treatment. Stunted growth and delayed puberty are conspicuous features of chronic renal failure (CRF). As another model of delay of growth and development, serum SHBG and serum T fractions were determined in 13 boys with CRF on chronic dialysis. In CRF, mean serum SHBG was significantly higher (99.1 +/- 68.9 nmol/L; P less than 0.05) than in 31 control (C) children of similar ages (66.2 +/- 34.9 nmol/L), while serum non-SHBG-bound T and free T were significantly lower (0.16 +/- 0.12 in CRF vs. 0.24 +/- 0.12 in C and 0.010 +/- 0.005 in CRF vs. 0.016 +/- 0.01 in C, respectively). On the other hand, serum total T (1.31 +/- 0.88 in CRF vs. 1.08 +/- 0.56 in C) and serum insulin-like growth factor-I (IGF-I; 1.06 +/- 0.74 in CRF vs. 1.35 +/- 1.70 in C) were not significantly different. A significant negative correlation between serum SHBG and chronological age as well as a significant positive correlation between serum non-SHBG-bound T and chronological age were found. For a given age, serum SHBG was higher, while serum non-SHBG-bound T was lower in patients with CRF (by analysis of covariance, P less than 0.01). It is postulated that, as has been proposed for hypopituitary boys, this delayed increment in serum T fractions could be responsible for the delay in the onset of puberty reported in CRF. It is known that GH decreases serum SHBG, acting on hepatic cells either directly or through the action of IGF-I. Since it has been suggested that patients with CRF have peripheral resistance to GH or IGF-I, the high levels of SHBG that we have detected in prepubertal boys with CRF could be taken as an additional evidence of this biological resistance.

Adolescent↗
PubMed1989

Decrease of serum sex hormone-binding globulin as a marker of androgen sensitivity. Correlation with clinical response.

An evaluation of the usefulness of determining the decrease in serum sex hormone-binding globulin after exogenous testosterone was studied in 55 prepubertal patients with ambiguous external genitalia or micropenis. The biochemical response (androgen sensitivity test) was compared with the clinical response as judged by signs of androgen stimulation of external genitalia. Patients were divided in two groups according to age. Group I, 11 patients younger than 3 months and Group II, 44 patients older than 3 months. Only in 54% of Group I was there a correlation between the androgen sensitivity test and the clinical response to androgens in either a positive (4 patients) or negative sense (2 patients). On the other hand, the androgen sensitivity test and the clinical response to androgens correlated in 91% of the patients of Group II in either a positive (35 patients) or negative sense (5 patients). Two of the 4 patients with lacking correlation had a negative androgen sensitivity test and micropenis secondary to pituitary deficiency. It is concluded that in prepubertal patients older than 3 months with abnormalities of sex differentiation, the androgen sensitivity test and the clinical response to androgens are useful for evaluating androgen sensitivity. The clinical response to androgens is useful in early life when a positive response is found.

Chorionic Gonadotropin↗
PubMed1989

Lack of correlation of serum estradiol with growth velocity during male pubertal growth.

The adolescent growth spurt in boys is under hormonal control. It is accepted that androgens and growth hormone contribute to male pubertal growth, but the role of estrogens is uncertain even though low-dose estradiol administration stimulates growth in prepubertal boys. In the present work, the correlation of serum testosterone and serum estradiol with growth velocity was studied in 16 pubertal normal boys. The study included correlations of growth velocity with serum nonsex hormone-binding globulin-bound testosterone and with serum nonsex hormone-binding globulin-bound estradiol, which are parameters of serum bioavailable sex hormones. A statistically significant positive correlation was found between serum testosterone and growth velocity but not between serum estradiol and growth velocity. These findings are against the hypothesis that estrogens play a growth promoting role during male puberty.

Adolescent↗
PubMed1989

Changes in the distribution of testosterone and estradiol serum fractions in hirsute women after administration of L-thyroxine.

The effect of 1-thyroxine treatment on the distribution of testosterone and estradiol serum fractions was studied in 10 normal weight hirsute women with ages ranging from 18 to 25 years. Six of the patients had menstrual irregularities. Treatment consisted in one month of thyroxine (1-T4) at a dose of 2 micrograms/Kg body weight. Serum sex hormone binding globulin (SHBG) was measured by saturation analysis and serum testosterone (T), estradiol (E2), androstenedione (delta 4-A), dehydroepiandrosterone sulphate (DHAS), LH, FSH, PRL, T4, T3, by RIA. Serum T and E2 fractions were calculated by an equation derived from the law of mass action. Before and after T4 treatment serum SHBG was, respectively, (X +/- ES) 30.3 +/- 3.8 and 45.4 +/- 4.6 nmol/l (p less than 0.001), non-SHBG-bound T 25.7 +/- 8.1 and 18.8 +/- 6 ng/dl (p less than 0.001), free T 1.09 +/- 0.2 and 0.8 +/- 0.5 ng/dl (p less than 0.01), non-SHBG-bound E2 40.9 +/- 13.7 and 19.2 +/- 2.4 pg/ml (p less than 0.001). No significant changes were observed in total T and E2 or free E2. Serum DHAS and delta 4-A decreased significantly after treatment from 3977 +/- 601 to 3480 +/- 250 ng/dl and from 4.7 +/- 0.61 to 3.34 +/- 0.34 ng/ml respectively (p less than 0.001). Serum basal levels of FSH, LH, PRL, T4, T3 and TSH were normal. A significant increase of serum T4 was observed after treatment from 8.4 +/- 0.4 to 11.7 +/- 1.1 ng/dl (p less than 0.01). However, the post-treatment value was within the limits of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Progressive increase in nonsex hormone-binding globulin-bound testosterone and estradiol from infancy to late prepuberty in girls.

We previously reported that serum sex hormone-binding globulin (SHBG) decreases and serum non-SHBG-bound testosterone (T) increases with age in normal prepubertal boys from infancy to late prepuberty. In this study we measured serum SHBG, T, estradiol (E2), and dehydroepiandrosterone sulfate (DS), and we calculated serum non-SHBG-bound T and E2 and free T and E2 in 22 normal prepubertal girls, aged 1-9.4 yr. The girls were divided into 3 groups of different ages: group A, 1.7 +/- 1.0 (mean +/- SE) yr; group B, 4.6 +/- 0.8 yr; and group C, 7.3 +/- 0.8 yr. In group C, mean serum SHBG level was lower, and serum T, non-SHBG-bound T, free T, DS, total E2, non-SHBG-bound E2, and free E2 were higher than in group A or B. Furthermore, a negative correlation was found between serum SHBG and age [y(nmol/L) = 144 - 9.07 x (yr); r = 0.57; P less than 0.001], while positive correlations were found between non-SHBG-bound T and age [y(nmol/L = 0.043 + 0.023 x (yr); r = 0.68; P less than 0.001], non-SHBG-bound E2 and age [y(pmol/L) = 0.69 + 2.82 x (yr); r = 0.6; P less than 0.001], and DS and age [y(nmol/L) = 25.2 + 63.8 x (yr); r = 0.59, P less than 0.001]. In a group of 19 normal age-matched prepubertal boys, we also found a significant correlation between non-SHBG-bound E2 and age. Since non-SHBG-bound sex hormone levels are good indicators of tissue available sex hormones, we conclude that in prepubertal girls, there is a progressive increase in the exposure of peripheral tissues to T and E2 with advancing age. Since sex hormones enhance tissue maturation, these increments might play a role in the somatic and psychic development of girls before the onset of the clinical signs of puberty.

Age Factors↗
PubMed1987

Changes in serum sex hormone-binding globulin and in serum non-sex hormone-binding globulin-bound testosterone during prepuberty in boys.

Much evidence suggests that sex hormone-binding globulin (SHBG) influences the delivery of sex steroids to cells, probably by playing an important role in the distribution of serum sex hormones between SHBG-bound, albumin (HSA)-bound and free fractions. Recent evidence also suggests that HSA-bound testosterone (T), the major constituent of non-sex hormone-binding globulin-bound T, is biologically important. To examine the potential exposure of peripheral tissues to T during prepubertal years, the serum concentration of SHBG as well as the distribution of serum T in SHBG-bound, HSA-bound, free and non-SHBG-bound fractions was studied in 80 normal boys aged 0.5-14 yr, all at Tanner's stage G1 of sexual development. A gradual decrease in serum SHBG as a function of age was found without significant changes in the Ka of SHBG-dihydrotestosterone association. While regression analysis of serum total T vs age showed a 2.6-fold increase from 0.5 to 14 yr of age, those of non-SHBG-found, HSA-bound and free T vs age showed 8- to 9-fold increases during the same period. On the other hand, SHBG-bound T had only a 1.9-fold increase. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6 to 30.4%, the relative increment being greater for HSA-bound T than for free T. It is concluded that, with advancing age, there is a progressive increase in the T exposure of all tissues in normal prepubertal boys. It is speculated that, at the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.

Adolescent↗
PubMed1987

Validity of the calculation of non-sex hormone-binding globulin-bound estradiol from total testosterone, total estradiol and sex hormone-binding globulin concentrations in human serum.

Recent evidences indicate that biologically available serum testosterone (T) and estradiol (E2) include not only the free fractions but also most of the albumin-bound fractions. These two serum T or E2 fractions constitute most of non-sex hormone-binding globulin (SHBG)-bound T or E2, respectively. It has been reported that the estimation of serum non-SHBG-bound T gives identical results when it is assayed experimentally or when it is calculated by a formula derived from the law of mass action assuming two binding systems (T-SHBG and T-albumin). In the present work, we have compared the results of the experimental measurement of non-SHBG-bound E2 with the calculated value derived by an equation based on the law of mass action considering four binding systems (E2-SHBG, T-SHBG, E2-albumin, T-albumin). It was found that the two estimations of non-SHBG-bound E2 correlated closely in normal men (r = 0.80), normal women (r = 0.90) and hirsute women (r = 0.98). When compared with a more complex calculation which includes 21 steroids and 3 binding proteins results also agreed closely. Values for the different T and E2 fractions in these groups of subjects are given. These calculations could be used, not only for clinical research, but also in clinical practice as an useful tool for evaluation of the sex hormone status of patients.

Estradiol↗
PubMed1987

Progressive increase in non-sex-hormone-binding globulin-bound testosterone from infancy to late prepuberty in boys.

Recent evidence suggests that human albumin-bound testosterone (HSA-bound T), the major constituent of nonsex hormone-binding globulin-bound T (non-SHBG-bound T), is biologically important. To examine the potential exposure of peripheral tissues to T in normal prepubertal boys, we determined the distribution of serum T into SHBG-bound, HSA-bound, non-SHBG-bound, and free fractions in 80 normal males, aged 0.5-14 yr, all at Tanner stage I of sexual development. A model assuming equilibrium between free T and T bound to 2-binding proteins (HSA and SHBG) was used. A computer program, using as constants the SHBG-T and HSA-T affinity constants and the serum HSA concentration and as variables the serum SHBG and total T concentrations, was used to calculate SHBG-bound T, HSA-bound T, non-SHBG-bound T, and free T. Serum total T increased 2.6-fold from 0.5 to 14 yr, whereas non-SHBG-bound T, HSA-bound T, and free T increased 8- to 9-fold during the same period. On the other hand, SHBG-bound T increased only 1.9-fold. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6% to 30.4%, the relative increment being greater for HSA-bound than for free T. We conclude that with advancing age, there is a progressive increase in the exposure of all tissues to T in normal prepubertal boys. At the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.

Adolescent↗
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↗