Search PubMed⌕ Search

Biomedical subjects

A Belgorosky

Publications and source records attributed to A Belgorosky.

At least 37 records · Page 2Linked to original sources

Testicular steroid biosynthesis in a boy with a large cell calcifying Sertoli cell tumor producing prepubertal gynecomastia.

A study of a large cell calcifying Sertoli cell tumor of the testis associated with bilateral gynecomastia in an 8-year-old boy is presented. Macroscopically, the two testes showed multiple, large, and hard calcified nodules. Histology revealed clusters or cords of tumor cells with foci of calcifications as well as evidences, in the adjacent testicular parenchyma, of initiation of gonadal development, such as early signs of spermatogenesis and sparse Leydig cell differentiation. In vivo, serum hormone studies showed gonadotropin-independent gonadal activity. After orchidectomy two macroscopically distinct fractions of the removed testes, tumoral and extratumoral, were processed separately for cell isolation and culture. The secretion of testosterone, androstenedione, and 17-hydroxyprogesterone to the medium on day 6 of culture showed that steroidogenesis in cells of the extratumoral fraction was more active than in the tumoral fraction. On the other hand, tumoral fraction cells showed much higher aromatase activity than extratumoral cells. Furthermore, conditioned medium of tumoral fraction cells was able to stimulate testosterone secretion when it was added to subcultures of testicular cells isolated from a control subject. It is postulated that tumoral cells might have stimulated neighboring interstitial cells to differentiate into Leydig cells and to secrete androgens, which in turn might have been aromatized to estrogens by tumoral cells.

Adult↗

Human prepubertal testicular cells in culture: steroidogenic capacity, paracrine and hormone control.

The neonatal human Leydig cell undergoes a transient period of activation during the first months of life. The biological significance of this activation is unknown. Furthermore, little is known about the hormonal regulation of this biological process, even though it coincides with an elevation of LH levels in serum. In order to study the function of human prepubertal testicular culture cells, obtained during the neonatal period, a method for maintaining primary culture cells (isolated from testes collected at necropsy) in culture was developed. Within 24 h after death, testes were collected from 1-36-month-old subjects. Subjects were divided into two age groups, based on the presence or absence of fetal Leydig cells: 1-7-month-old infants (group 1) and 12-36-month-old children (group 2). Testes were digested with collagenase, and cells were seeded in multi-well dishes. Cells were grown in serum-free conditioned media supplemented with 5 mg/l vitamin C, 0.2 IU/l vitamin E and 10% fetal bovine serum for 2 days. Cells were then grown for an additional 4 days in serum-free media in the presence or absence of hLH (40 IU/l), hCG (135 IU/l), rh FSH (1.5 IU/l), rhGH (0.12 IU/l) or insulin (0.9 mumol/l). Concentrations of steroids in media were determined by RIA on day 6 of culture. In basal conditions cells of group 1 (n = 11) secreted more testosterone, androstendione, 17-hydroxyprogesterone, progesterone and dehydroepiandrosterone (mean +/- SE: 6.76 +/- 1.86, 7.37 +/- 1.82, 61.9 +/- 1.86, 5.75 +/- 1.74 and 8.51 +/- 3.23 pmol/10(6) cells/24 h, respectively) than cells of group 2 (n = 5) (2.95 +/- 1.15, 1.50 +/- 2.75, 1.44 +/- 2.75, 0.78 +/- 1.74 and 3.23 +/- 1.32, respectively). Under hLH stimulation, cells of group 1 increased testosterone, androstendione and 17-hydroxyprogesterone secretions (to 38.2 +/- 0.89, 13.5 +/- 1.17 and 51.7 +/- 3.23), while progesterone secretion remained unchanged (2.82 +/- 1.20). Cell response to rhFSH and rhGH was similar to that of hLH. On the other hand, medium collected from cultures of cells isolated from a Sertoli cell tumor was able to stimulate testosterone secretion in subcultures of control testicular cells in a way similar to that of hCG. In conclusion, (1) these prepubertal human testicular cells can be maintained in primary culture for several days keeping their in vivo steroidogenic potential; (2) cells isolated from young infants can respond to hLH in culture; (3) response to rhFSH is probably mediated by a paracrine factor; (4) response to rhGH is observed in the absence of gonadotropins.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Basal testosterone secretion and response to human luteinizing, follicle-stimulating, and growth hormones in culture of cells isolated from testes of infants and children.

Little is known on the hormonal regulation of the early postnatal phase of Leydig cell activation in the human. Testosterone secretion by prepubertal testicular cells in culture was studied in two different age groups, 0-7-mo-old (group 1) and 16-36-mo-old (group 2) boys. A mixed cell preparation was isolated from testes collected at necropsy and maintained in culture for 6 d. Cells were cultured in serum-free medium in basal conditions and under the stimulation of human (h)LH, hFSH, or recombinant hGH, and the secretion of testosterone was determined on d 6 by RIA. In basal conditions, cells of group 1 secreted more testosterone (median 5.83 pmol/10(6) cells.d, n = 7) than cells of group 2 (median 1.73, n = 5), p < 0.05, reflecting the steroidogenic potential of the testes in vivo. Under hLH stimulation, cells of group 1 responded by increasing testosterone secretion significantly. Surprisingly, hFSH stimulation elicited a similar response in cells of group 1. Because FSH receptors are presumably located in Sertoli cells, it is concluded that these cells secreted a paracrine factor that stimulated testosterone secretion by Leydig cells. On the other hand, recombinant hGH also stimulated the secretion of testosterone by cells of group 1. Recombinant hGH could have interacted with either GH or prolactin receptors of testicular cells. Cells of group 2 did not respond to any stimulus. Because serum levels of LH, FSH, GH, and prolactin are higher during the first months of life than later in childhood, it is possible that the early postnatal activation of the testis is under multiple pituitary hormone influence.

Age Factors↗

Hypothalamic-pituitary-gonadal function in prepubertal boys and girls with chronic renal failure.

Hypothalamic-pituitary-gonadal function was evaluated in 24 prepubertal children with chronic renal failure (CRF). Among the 17 boys, 5 were receiving conservative treatment and four long-term dialysis. Another eight boys were studied 6 months to 3.3 years after renal transplantation; their ages ranged from 5 years 8 months to 15 1/2 years. Among the girls, two patients were receiving conservative treatment and five long-term dialysis; their ages ranged from 3 1/2 years to 11 years 2 months. In boys with CRF, but not in those after transplantation, mean serum follicle-stimulating hormone 60 minutes after administration of gonadotropin releasing hormone (GnRH) was lower than in 18 control prepubertal boys (mean +/- SD: 2.53 +/- 1.34 vs 6.25 +/- 2.84 IU/L, respectively; p < 0.01). Testosterone steroidogenic capacity after 1 week of stimulation with human chorionic gonadotropin and androgen sensitivity (percentage of decrease of serum sex hormone-binding globulin 1 week after intramuscular administration of testosterone enanthate) were normal. In girls, no difference between those with CRF and a control group of 19 girls was found after intravenous administration of GnRH. However, after intramuscular administration of GnRH agonist, serum follicle-stimulating hormone concentration was lower in girls with CRF than in control girls (p < 0.02); six of seven control girls had an increase of serum estradiol to more than 55 pmol/L, whereas three of seven girls with CRF had no response, and serum follicle-stimulating hormone failed to increase after GnRH agonist therapy in two of these patients. We conclude that hypothalamic-pituitary function is not normal in some prepubertal boys and girls with CRF, particularly in those with low serum albumin concentrations. On the other hand, testicular and ovarian steroidogenic capacity is not impaired, and the biologic response to androgens in boys is preserved.

Adolescent↗

Differences in serum insulin-like growth factor I and sex-hormone-binding globulin levels between late and early prepuberty in patients with idiopathic and organic growth hormone deficiency.

It has been reported that growth hormone modulates serum levels of insulin-like growth factor I (IGF-I) positively and serum levels of sex-hormone-binding globulin (SHBG) negatively. We have measured IGF-I and SHBG concentrations in 24 prepubertal patients with growth hormone deficiency. Twelve of these patients had had intracranial tumors removed (organic growth hormone deficiency) and 12 had growth hormone deficiency of unknown etiology (idiopathic). Fifty-two prepubertal control subjects, admitted for elective surgery, were also studied. All prepubertal patients were divided into two age groups: older and younger than 7 years of age. In both groups there were patients with multiple pituitary deficiencies on hydrocortisone and/or levothyroxine sodium replacement therapy. In the age group younger than 7 years, serum IGF-I was not significantly different between organic and idiopathic growth hormone deficiency (0.28 +/- 0.21 versus 0.062 +/- 0.071 mU/l) but serum SHBG levels were different (74.6 +/- 33.5 versus 173 +/- 59 nmol/l, p < 0.05). These values were not significantly different from controls (0.47 +/- 0.25 mU/l and 132 +/- 47 nmol/l, respectively). In the age group older than 7 years, there was no significant difference between organic and idiopathic growth hormone deficiency in serum IGF-I (0.33 +/- 0.17 versus 0.16 +/- 0.11 mU/l) or serum SHBG (113 +/- 72 versus 108 +/- 17 nmol/l). These values were significantly different from controls (1.04 +/- 0.36 mU/l and 68.7 +/- 31.7 nmol/l, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗