Absent B-endorphin response to clonidine in obese children

Plasma B-Endorphin (B-EP), Growth Hormone (GH) and cortisol response to 100 mcg/m2 b.s., i.v. clonidine (an alpha 2-adrenergic agonist) were evaluated in 17 normal weight children (8 prepubertal and 9 pubertal) and in 15 children with simple exogenous obesity (7 prepubertal and 8 pubertal, weight excess ranging from 29% to 97%). All the hormones were measured by radioimmunoassay either directly in the plasma (GH and cortisol) or after extraction and chromatography (B-EP). Obese prepubertal and pubertal children showed basal B-EP levels significantly higher than in controls and no differences were found in GH and cortisol levels. While in controls clonidine stimulated a significant release of plasma GH and B-EP in obese patients, irrespective of pubertal development, no changes were found. Cortisol levels decreased in both groups. These data suggest an impaired adrenergic control of GH and B-EP secretion in children with simple exogenous obesity.     

Physical activity,energy expenditure and intake in 11 to 12 years old Japanese prepubertal obese boys

The purpose of this study is to find out the differences in physical activity (PA), energy expenditure (EE) and energy intake (EI) under free-living conditions between Japanese prepubertal obese and nonobese boys. The subjects were 15 prepubertal obese boys (Age: 11.7+/-0.4 years old, Body fat: 35.2+/-1.6%) who do not have obese parents and siblings and 15 prepubertal nonobese boys (Age: 11.8+/-0.4 years old, Body fat: 18.5+/-0.8%). We assessed their daily PA by heart rate (HR) monitoring, pedometer step counts (PSC) and time for sedentary activities (SA). We also examined calculated EE from HR-VO(2) regression, EI and percentage of macronutrient EI. Results are as follows: Percentage of body fat had significant correlation with weight, BMI, time for SA, percentage EI of protein (positive, p<0.001), VO(2max), VO(2max) per body weight, VO(2max) per LBM, PSC, TEE per body weight, TEI per body weight (negative, p<0.001), percentage of EI of carbohydrate (negative, p<0.01). The values of the obese were significantly lower in total EE per body weight and in total EI per body weight. EI from dinner was significantly higher in the obese group. The values of the obese were significantly higher in percentage EI from protein and that from carbohydrate. The results of this study showed prepubertal obese boys who do not have obese parents and siblings have low PA and spend much time for sedentary activities. Obese boys consume higher percentage energy of protein and lower percentage of carbohydrate though differences in EE and EI were found only in total EE per body weight and total EI per body weight between obese boys and nonobese boys.     

Effect of infusion of gonadotropin releasing hormone upon plasma concentrations of sex hormones in prepubertal and pubertal males.

Plasma testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17OHP), androstenedione (A), estradiol (E2), and dehydroepiandrosterone sulfate (DHAS) were measured by radioimmunoassay after celite chromatography prior to and after a 3-hour infusion of the synthetic gonadotropin releasing factor, GnRH, in normal prepubertal and pubertal boys. Plasma T levels rose (p less than 0.001) in the pubertal but not prepubertal boys. 17OHP concentrations increased in those boys who had an increment of T. A, DHT, E2 or DHAS levels did not increase after GnRH. Basal levels of T, DHT, A and DHAS correlated with the peak and mean serum LH levels attained during the GnRH infusion. These data confirm the greater Leydig cell responsivity to transient rises of endogenous gonadotropin in pubertal males and also suggest that there may be a relationship between adrenal androgen production and maturation of the hypothalamic-pituitary-gonadal system.     

Calcitonin gene-related peptide in human obesity.

We studied plasma calcitonin gene-related peptide (CGRP) levels in obese women before (n = 24) and after (n = 13) weight loss, and in normal weight controls (n = 15). Furthermore, the influence of two isocaloric meals (high carbohydrate vs. high fat) on plasma CGRP concentrations was studied. The CGRP concentration in the obese group (32.26 +/- 2.01 pg/ml) was significantly (p less than 0.0001) higher than in the control group (21.64 +/- 0.15 pg/ml). After weight loss (14.3 +/- 0.72% of original weight) CGRP concentrations remained unchanged. Only the high-fat meal caused a significant (p less than 0.02) rise in CGRP levels. Our results indicate that elevated plasma CGRP levels may constitute a primary phenomenon in obese women, and that fat intake may be associated with increased CGRP secretion.     

Sex‐Specific Fat Distribution Is Not Linear Across Pubertal Groups in a Multiethnic Study

Objective: To investigate sexual dimorphism and race differences in fat distribution (android/gynoid) before and during puberty. Research Methods and Procedures: Fat distribution was measured by skinfold thickness and DXA in healthy African‐American, Asian, and white subjects (n = 920), divided into pre‐, early, and late pubertal groups. Results: Gynoid fat masses adjusted for covariates were lower in late pubertal compared with prepubertal boys, but were not consistently greater in late pubertal compared with prepubertal girls. Progression of sex‐specific fat distribution with increasing maturation was present in Asians only. Among African‐American and white subjects, early pubertal boys had greater gynoid fat mass compared with the prepubertal group, whereas early pubertal girls had less gynoid fat mass compared with the prepubertal group. Sexual dimorphism in fat distribution was present in all pubertal groups, except among whites at early puberty. Among girls, Asians had lower gynoid fat than whites and African Americans in all pubertal groups. Among boys, Asians had less gynoid fat by DXA in early puberty and late puberty. Discussion: Comparison among races demonstrated differences in sexual dimorphism and sex‐specific fat distribution with progression in pubertal group. However, in all race groups, the fat distribution of late pubertal boys was more “male” or “android” than prepubertal boys, but late pubertal girls did not differ consistently from prepubertal girls. These findings suggested that the greater sexual dimorphism of fat distribution in late puberty compared with prepuberty may be attributable to larger changes in boys with smaller changes in girls.     

Altered sexual development in male rats after oestrogen administration during the neonatal period.

Male rats given 250 mug oestradiol benzoate by subcutaneous injection on Day 4 of postnatal life showed a marked delay in the onset of the pubertal increase in the weight of the testes and seminal vesicles and in spermatogenesis but not a complete failure of sexual development. The increase in plasma testosterone concentration at puberty was also delayed in oestrogen-treated males but the eventual increase in seminal vesicle weight was closely related in time to the delayed increase in plasma testosterone concentration. Both plasma LH and FSH concentrations were reduced for about 10 days after oestrogen administration as compared to control values. After 22 days of age, plasma LH concentration did not differ significantly from the control values. The plasma FSH concentration of the oestrogen-treated males showed a delayed rise to values equal to or higher than those of controls of the same age. The delayed rise in plasma FSH concentration in the oestrogen treated males preceded the delayed rise in plasma testosterone in these animals. The decrease in plasma FSH concentration from the high prepubertal values to the lower values in adults occurred at different ages in the control and in oestrogen-treated rats but in both groups the decrease occurred as plasma testosterone levels were increasing and the first wave of spermatogenesis was reaching completion. The increase in plasma FSH concentration after castration was reduced in oestrogen-treated males during the period throughout which FSH levels in the intact animals were subnormal but the levels in oestrogen-treated males castrated after the delayed rise in FSH had occurred did not differ from control values. It is suggested that the delayed sexual maturation of male rats treated with high doses of oestrogen in the neonatal period is related principally to abnormalities in the secretion of FSH.     

The role of estrogen in bone growth and maturation during childhood and adolescence

Twenty years ago it was believed that pubertal growth was stimulated by testicular androgen in boys and by adrenal androgen in girls. Estrogen, which was used to inhibit growth in excessively tall girls, was not thought to have growth-promoting effects. We hypothesized that estrogen has a biphasic effect on epiphyseal growth, with maximal stimulation at low levels. We showed that the administration of low doses of estrogen, corresponding to a serum estradiol level of about 4 pg/ml (15 pmol/l) caused more than a 60% increase over the prepubertal growth rate in both boys and girls. To test the hypothesis that estrogen is the principal mediator of the pubertal growth spurt in boys, we administered the aromatase inhibitor, testolactone, to boys with familial male-limited precocious puberty. Testolactone produced near normalization of both growth velocity and bone maturation, despite levels of serum testosterone that remained within the adult male range. The observation that low levels of estrogen stimulate growth and bone maturation suggested that estrogen might explain the more rapid epiphyseal maturation of prepubertal girls compared to boys. To determine whether prepubertal girls have higher estrogen levels than prepubertal boys, we developed an ultrasensitive recombinant cell bioassay for estrogen with a sensitivity of 0.02 pg/ml (0.07 pmol/l) estradiol equivalents. Prepubertal girls had approximately eight-fold higher levels of serum estradiol than did prepubertal boys (0.6 ± 0.6 pg/ml (SD) (2.2 ± 2.2 pmol/l) vs 0.08 ± 0.2 pg/ml (0.29 ± 0.73 pmol/l), P < 0.05). We concluded that the pubertal growth spurt of both sexes is driven primarily by estrogen, and that the more rapid epiphyseal maturation of prepubertal girls (vs boys) may be explained by their higher estradiol levels.     

Plasma androgens in children and adolescents. Part I: control subjects

In this cross-sectional study, plasma levels of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), delta 4-androstenedione (delta 4) and testosterone (T) were measured by RIA in 232 normal subjects of both sexes, aged 2 weeks to 20 years. The results were analyzed in relation to chronological age, body surface and pubertal stage. High levels of plasma androgens were found in newborn infants of both sexes. After 3 months of age, androgen levels were uniformly low and rose with increasing chronological age and body surface. The first significant increase in mean androgen levels was found for DHEA-S. It occurred after 6 years of age in girls and after 8 years in boys. DHEA and T rose in both sexes after 8 years of age. delta 4 increased steadily with chronological age and body surface in both sexes. When androgen levels were related to body surface, a first significant increase was observed above 1.00 m2 for the four androgens, in both boys and girls. Above 1.20 m2 and 12 years of age, girls had higher mean levels of DHEA-S, DHEA and delta 4, but lower mean T levels than boys of the same body surface and chronological age. Before puberty, a positive correlation was found in both sexes between the plasma androgen levels on the one hand, and both chronological age and body surface on the other. Plasma androgen levels markedly increased at stage P2 in both sexes, and further increased with pubertal development. During puberty, girls had higher plasma delta 4, but lower plasma T levels than boys of the same pubertal stage. Plasma DHEA-S and DHEA levels were similar in both sexes. In contrast to the plasma androgens, plasma cortisol levels did not show any change in relation either to chronological age or to body surface or pubertal development. Body surface appears to be as good a discriminating factor as chronological age, at least in young children. It also appears from this study that DHEA-S is a good guide for the clinical evaluation of adrenal maturation and may be very useful in evaluating patients with growth or pubertal disturbances.     

Oxidative status and serum leptin levels in obese prepubertal children

The prevalence of obesity in children has increased dramatically over the last 20-30 years in developed countries. The aim of this study was to evaluate the oxidative and antioxidant status and any correlation with leptin in obese prepubertal children. A cross-sectional study was made of healthy children from ten elementary schools in the province of Elazig, Eastern Turkey. Blood samples were drawn from children comprising obese and control groups, on a visit to their school in the morning after an overnight fast. The mean body mass index (BMI) was 24.03 +/- 4.09 kg/m(2) in the obese group and was 17.51 +/- 2.33 kg/m(2) in the control group. Mean plasma leptin concentration was significantly higher in the obese children. Homocysteine and malondialdehyde (MDA) levels were also significantly higher in the obese group. In contrast superoxide dismutase (SOD) and glutathione peroxidase activities were significantly decreased in the obese group (p < 0.001). In conclusion, in prepubertal obese children oxidative stress was increased and MDA and homocysteine levels were well correlated with serum leptin level and BMI. In contrast with the increase in oxidative stress, antioxidant activities of SOD and glutathione peroxidase were decreased in obese prepubertal children.     

Cardiac Function During Exercise in Obese Prepubertal Boys: Effect of Degree of Obesity

The purpose of the study was to evaluate the dynamics of diastolic and systolic function from rest to maximal exercise using conventional echocardiography and tissue Doppler imaging (TDI) in obese prepubertal boys compared to age‐matched lean controls. Eighteen obese (10 with first degree obesity and 8 with second degree obesity according to French curves, BMI: 23.3 ± 1.8 and 29.0 ± 2.0 kg/m², respectively) and 17 lean controls (BMI = 17.6 ± 0.6 kg/m², P < 0.001), aged 10–12 years were recruited. After resting echocardiography, all children performed a maximal exercise test. Regional diastolic and systolic myocardial velocities were acquired at rest and each workload. Stroke volume and cardiac output were calculated. At rest, obese boys had greater left ventricular (LV) diameters and LV mass. Boys in the first degree group showed no diastolic or systolic dysfunction, whereas boys with second degree obesity showed subtle diastolic dysfunction. During exercise, both obese groups showed greater stroke volume and cardiac output. First degree obese boys exhibited greater systolic and diastolic tissue Doppler velocities than controls, whereas second degree obese boys had lower diastolic tissue velocities irrespective of exercise intensity and lower fractional shortening at high exercise intensities than controls. In conclusion, no impairment in diastolic or systolic function is noticed in prepubertal boys with first degree of obesity. Enhanced regional myocardial function response to exercise was also demonstrated in this population, suggesting adaptive compensatory cardiac changes in mild obesity. However, when obesity becomes more severe, impaired global and regional cardiac function at rest and during exercise can be observed.     

Plasma Leptin and Acute Serotoninergic Stimulation of the Corticotropic Axis in Women Who Are Normal Weight or Obese

OPPERT, JEAN-MICHEL, NAJIBA LAHLOU, BLANDINE LAFERRÈRE, MARC ROGER, ARNAUD BASDEVANT, BERNARD GUY-GRAND. Plasma leptin and acute serotoninergic stimulation of the corticotropic axis in women who are normal weight or obese. In some recent studies, glucocorticoid treatment was associated with rapid induction of obese (ob) gene expression in adipose tissue of normal rats and in isolated adipocytes. We studied the effect of acute stimulation of the corticotropic axis on plasma leptin, the ob gene product, in 7 women of normal weight and 12 women with obesity. Under double-blind, placebo-controlled conditions, a single 12.5-mg dose of clomipramine, a serotonin uptake inhibitor, was administered intravenously in 15 minutes. Mean basal plasma leptin was increased more than 3-fold in subjects with obesity compared with subjects of normal weight (35.1 ± 4.9 ng/mL vs. 8.9 ± 1.4 ng/mL, p=0.001). Whereas corticotropin (ACTH) and Cortisol responses were increased in women who were obese compared with women who were lean, no significant effect of clomipramine infusion was found on plasma leptin concentrations measured during the following 150 minutes in both groups. There was a strong positive correlation between basal plasma leptin concentrations and body mass index (r=0.92, p<0.0001). In six subjects with obesity studied after a moderate weight loss, mean basal plasma leptin was significantly decreased (43.7 ± 6.4 ng/mL before vs. 28.0 ± 8.1 ng/mL after, p=0.04), but the hormonal response pattern to clomipramine administration was unchanged. We conclude that, at least in the short term, an acute stimulation of the corticotropic axis does not seem to increase leptin secretion in humans, as shown by the response to the serotoninergic agent clomipramine.     

Study of insulin-like growth factor I in human obesity.

In obesity there is a decrease in basal and stimulated GH secretion. IGF-I, which has negative feedback effects on GH secretion, could be the initial mediator of such alterations. We studied IGF-I levels in obese subjects and their relationship to the obesity level and GH secretion. We determined plasma IGF-I, basal and stimulated GH in 30 normal and 30 obese women and related these variables to obesity indices (body mass index, BMI, and % overweight). Baseline plasma GH values were 1.2 +/- 0.3 and 2.3 +/- 0.6 micrograms/l in obese subjects and controls, respectively (NS). Mean peak GH secretion after stimuli were 11.2 +/- 1.4 and 34.4 +/- 5.6 micrograms/l in obese subjects and controls, respectively (p less than 0.001). Plasma IGF-I were 1.0 +/- 0.1 U/ml and 0.7 +/- 0.1 U/l in obese subjects and controls, respectively (NS). There was a significant negative correlation between plasma IGF-I and age (r = -0.55, p less than 0.001) and a significant negative correlation between mean peak GH secretion and weight (r = -0.60, p less than 0.001), BMI (r = -0.64, p less than 0.001) and percentage of ideal body weight (r = -0.67, p less than 0.001). We did not find any correlation between IGF-I and indices of overweight. These data suggest that the reduced GH secretion found in obesity is not related to a negative feedback inhibition by elevated levels of IGF-I and that adiposity is not associated with a decline in IGF-I levels. We confirm the existence of a negative correlation between GH secretion and obesity indices.     

La puberté surrénalienne

The androgens produced by the adrenal glands are mainly Δ5 steroids, first dehydroepiandrosterone (DHA) and its sulfate (DHAS). Adrenal androgens, very high at birth, decrease rapidly the first few months of life, remaining very low from 1 to 6 years of life. Adrenarche is defined as the changes in the pattern of adrenal secretions which occur several years before the onset of gonadal puberty (gonadarche). Developmental patterns of adrenal androgens differ markedly among species and only the chimpanzee exhibits an adrenarche comparable to that of man. Adrenarche starts in both sexes around age 7. The increase in DHA/DHAS has a rather abrupt onset and is thereafter progressive. Before the onset of gonadarche mean levels of DHA and DHAS have increased by about 10 and 20 fold respectively. The prepubertal rise in plasma Δ⁵-androgens is accompanied by that of Δ4-androstenedione and 11β-hydroxy-Δ⁴-androstenedione occurring likely at about the same time but being very progressive and more modest are only significant after age 8 in both sexes. Adrenal androgens continue to rise during puberty. Plasma levels of DHA and DHAS continue to rise from pubertal stages 1 to 5 and remain similar in both sexes until age 15. At pubertal stage P5, plasma DHA levels are similar to that seen in young adults with no sex difference while that of DHAS continue to rise in boys and become significantly higher than in girls. Developmental changes in adrenal androgen secretions are also observed in the response to ACTH stimulation. Whether estimated as absolute levels or Δ of response, the rise in all unconjugated adrenal androgens to a short or prolonged ACTH stimulation, is greater with increasing age, with no sex difference, and is somewhat correlated to basal levels. Plasma levels of DHAS do not vary significantly the 2 hours following a bolus injection of ACTH (21, 34) but its response to longterm (3-days) ACTH stimulation is also increasing with age. Morphological and functional changes in the adrenal cortex also occur during development. Focal development of aZona reticularis starts at 5 years of age, and progressively becomes continuous. The development of the zona reticularis is parallel to the increase in adrenal androgen secretions, and is completed only by age 15. This is accompanied by a rise in 17-hydroxylase and 17,20-desmolase activity in the adrenals. In a normal timing of physiological events, the onset of adrenarche occurs several years before the onset of gonadarche, 2–3 years in girls and 3–4 years in boys. This relation does not preclude that the processes are independent events. Indeed, the onset of adrenarche and gonadarche are dissociated in a variety of disorders of sexual maturation Adrenal androgen secretions are under the control of ACTH, as shown by a series of observations. However, the specific increase of adrenal androgen secretions during development without any detectable change in ACTH stimulation, the dissociation between adrenarche and gonadarche in several conditions, have led to postulate that the biochemical differentiation of the zona reticularis may require the action of an «adrenal factor» in addition to ACTH. Among the proposed «trophic» factors of adrenal androgen secretion, LH/FSH and estrogens are no longer believed to be involved. The evidences for the existence of a separate and specific pituitary cortical androgen-stimulating hormone (CASH) are not yet convincing. Prolactin, linked to nutritional status, may stimulate the activity of the adrenal hydroxysteroid sulfotransferase. The functional zonal theory» is attractive, but it does not explain why changes in adrenal androgens occur at a given age. Finally, the occurrence of familial cases of premature pubarche, the study of the changes in adrenal androgens in monozygotic or dizygotic twins and the observation that in idiopathic delayed puberty the delay in adrenarche is only one part of a generalized growth and developmental delay, strongly suggests that maturation of the adrenal cortex is regulated, at least in part, by genetic factors. The physiological importance of adrenal androgens remains a matter of controversy. Classical “dogma” dictates that adrenal androgens are responsible for pubic hair development. It has also been suggested that they contribute to somatic growth or epiphyseal advancement in childhood. This is mainly based on the observation that premature adrenarche is accompanied by premature pubarche, tall stature and advanced bone age. However, adequate androgen secretion alone does not ensure normal sexual hair development in many patients with gonadal dysgenesis. Moreover, in children with a lack or delayed adrenarche long-term treatment with DHAS at dosages such as to restore normal levels for age, failed to induce growth of sexual hair or any change in growth rate, bone maturation velocity, or to advance puberty. Although new hypotheses favour the view that Δ5-androgens, particularly Δ⁵-androstenediol, have some characteristic properties of estrogens, the physiological role of adrenal androgens, if any, remains to be established. DHAS may well be only a prohormone. There are ample evidences that all tissues possess active sulfatases which transform it into DHA, a steroid with high turn-over. Administration of DHA to experimental animals has shown beneficial effects on various endocrine-metabolic parameters, enhanced immunoprotective functions and reduced carcinogenesis. DHA prevents diabetes in genetically diabetic and obese mice. The importance ofin vivo andin vitro experimental findings is underscored by epidemiological data showing that low DHA levels are correlated with increased cardiovascular morbidity in men, breast cancer in women and a decline in immune competence. Human studies are at the moment controversial. It remains possible that DHAS influence breast cancer risk earlier in life, and/or that there are more complex interactions with other hormones or the intracellular metabolism of DHA/DHAS. Indeed, the tissue concentrations of DHAS may be important since it may act indirectly via its metabolism into estradiol or other steroids. Further long-term studies are needed to conclude whether DHA/DHAS are a youth fountain.     

Growth hormone secretion during sleep. II. Interrelationships between growth hormone secretion, insulin-like growth factor I and sex steroids

The serum levels of insulin-like growth factor I (IGF I), dehydroepiandrosterone sulfate (DHAS), testosterone (T) and estradiol (E2) have been measured in 78 prepubertal and 57 early pubertal patients referred for short stature, at the same time when their secretion of GH was evaluated both during nocturnal sleep and by two conventional stimulation tests. According to the results of GH measurements they were considered as having a normal secretion of GH (group I), a complete GH deficiency (group II), a partial GH deficiency (group III), low responses to stimuli with normal secretion during sleep (group IV) or a nocturnal neurosecretory dysfunction (group V). Though widely scattered, the IGF I levels showed the following characteristics: a significant increase at puberty from 0.77 to 1.29 U/ml (p less than 0.001) in the so-called endocrinologically normal patients of group I, not in the other groups; in the prepubertal patients of group I, a correlation of IGF I with chronological age (r = 0.47, p less than 0.005) and bone age (r = 0.52, p less than 0.002); significantly reduced IGF I levels in patients of group II having complete GH deficiency (p less than 0.001); no significant differences between prepubertal patients with partial or atypical GH deficiency from groups III, IV, V and prepubertal patients from group I; lower pubertal levels in groups III, IV, V than in pubertal patients from group I (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothalamic excitatory amino acid system during sexual maturation in female rats

The present results indicate that during sexual maturation the APOA-MBH from rats of 30 days of age released significantly higher quantities of GnRH than the tissue from 16-day-old rats (P < 0.01). The addition of NMDA, an agonist of the excitatory amino acids system (EAAs), to the medium after 30 min of incubation significantly increased (P < 0.01) the GnRH release in normal rats of both ages and this increase was significantly (P < 0.01) higher in 30-day-old rats (to 661%) than in rats of 16 days of age (to 273%). The administration of estrogen-progesterone (EP) to rats of 16 days of age did not modify the GnRH release response to NMDA. On the contrary, at 30 days of age EP administration significantly potentiated the GnRH release response to NMDA since while in the control group NMDA increased the GnRH release to 630%, in the EP-pretreated group this was to around 4700% (P < 0.01). EP pretreatment of prepubertal rats decreases the hypothalamic release of aspartate and glutamate, the excitatory amino acids involved in NMDA neurotransmission and glycine but increases EAAs release in peripubertal rats. On the basis of these results it is proposed that the increase in EAAs release by the hypothalamus is directly connected with the onset of puberty and that the maturation of the positive feedback effect of ovarian hormones on gonadotropin secretion is related to the maturation of the capacity of EP to increase hypothalamic EAAs. Before this maturational event EP inhibits EAAs release as well as gonadotropin release (prepubertal rats). NMDA receptor stimulation leads to a positive mechanism which increases the release of Asp and Glu from APOA-MBH both in prepubertal and peripubertal rats, but EP potentiates this mechanism only in peripubertal rats. This could be an additional neuroendocrine mechanism involved in the increase of gonadotropin during sexual maturation which induces the onset of puberty and the preovulatory discharge of these pituitary hormones.     

Unilateral cryptorchidism with compensatory hypertrophy of descended testicle in prepubertal boys.

5 prepubertal boys with unilateral cryptorchidism and compensatory hypertrophy of the descended testicle, 22 prepubertal boys with unilateral cryptorchidism and without CTH, and 14 prepubertal normal boys were submitted to LH-RH and to HCG tests in order to study the hormonal behaviour in CTH phenomenon before puberty. High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation. On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones.     

Adrenal steroidogenic defects in children with precocious pubarche.

The occurrence of nonclassical congenital adrenal hyperplasia among children with precocious pubarche is still a matter of debate. We studied the adrenal steroid response to ACTH stimulus (Synacthen, 0.25 mg i.v. bolus) in 26 Italian children (5 boys, 21 girls) who had presented pubic hair, without other signs of virilization, at ages ranging between 0.45 and 8.8 years. The control groups comprised 8 prepubertal children (5 boys, 3 girls) and 12 children at Tanner stage 2 for pubic hair development (1 boy, 11 girls). Two patients were diagnosed as having nonclassical congenital adrenal hyperplasia: 1 due to 21-hydroxylase deficiency, the other due to 3 beta-hydroxysteroid-dehydrogenase deficiency. The remainder, classified as having idiopathic precocious pubarche (PP), had adrenal androgens higher than normal prepubertal children and similar levels to those observed in early pubertal controls. In contrast to a recent report, we confirmed that mild adrenal enzymatic defects can occur in PP, and, consequently, the use of ACTH testing in children with PP seems to be recommended.     

Glucagon-like peptide 1 (GLP-1) secretion and plasma dipeptidyl peptidase IV (DPP-IV) activity in morbidly obese patients undergoing biliopancreatic diversion.

BACKGROUND: The physiological inhibitory control of glucagon-like Peptide 1 (GLP-1) on gastric emptying and the contribution of this peptide in the regulation of food intake as a satiety factor suggest that impaired secretion and/or activity of GLP-1 may be involved in the pathogenesis of obesity. We investigated food-mediated GLP-1 secretion as well as plasma activity of dipeptidyl-peptidase IV (DPP-IV), the enzyme responsible for rapid inactivation of the circulating peptide, in morbidly obese patients, before and after weight loss resulting from biliopancreatic diversion. METHODS: Twenty-two morbidly obese non-diabetic patients (BMI = 47.5 +/- 1.8) and 9 age-matched healthy volunteers were studied. A mixed meal (700 kcal) was administered to all subjects and blood samples were collected at 0, 15, 30, 60, 120 min for the determination of circulating glucose, insulin, GLP-1 (7 - 36 amide) concentrations and plasma DPP-IV activity. The patients repeated the test meal after 50 % overweight reduction resulting from surgical treatment (BMI = 33.8 +/- 1.1). RESULTS: While nutrient ingestion significantly increased plasma GLP-1 levels in the control group (30', 60': p < 0.01), the test-meal failed to modify basal peptide values in the obese patients, and an overall reduction in circulating GLP-1 occurred during the observation period (p < 0.001). Plasma DPP-IV activity in the same patients resulted as being significantly higher than controls, both at fasting and in response to the meal (p < 0.05). With respect to preoperative values, an overall increase in circulating GLP-1 levels occurred in all patients following biliopancreatic diversion (p < 0.001). Plasma DPP-IV activity, on the other hand, continued to be abnormally increased, even after considerable weight loss (p < 0.05 vs. controls). CONCLUSIONS: First: In morbid obesity, the accelerated inactivation of circulating GLP-1 could at least partially account for plasma peptide levels lower than normal, the defective availability of such a satiety factor possibly contributing to eating behaviour abnormalities; Second: plasma DPP-IV hyperactivity in the obese did not seem to be affected by the overweight degree, the increase in postoperative GLP-1 levels mainly resulting from hyperstimulation of GLP-1 secretory cells due to surgical manipulation of gastrointestinal tract. If the abnormally accelerated degradation of GLP-1 in obesity is confirmed, selective DPP-IV inhibitors could actually represent an ideal approach to obesity management.     

Age- and sex-related characteristics and mechanisms of adaptations during the prepubertal and pubertal periods of development

Integrated study of the functional state of the sympathoadrenal system and the adrenal cortex in children of both sexes aged 10–15 years. The study was conducted on the basis of the daily adrenaline, noradrenaline, 17-ketosteroid, and 17-oxycorticosteroid excretion values, which allowed certain synchrony to be established in the manifestation of the activity of the transmitter link of the sympathoadrenal system and the adrenal cortex androgenic and glucocorticoid functions with age, during sexual maturation. The heterogeneous character of maturation was found in the sex groups: in girls at an age of 10 and 12 years and in the boys at an age of 14–15 years. Changes in the excretion of the hormones and hormone metabolites with different directions and rates in the age-sex groups were observed throughout the academic year. In 14- to 15-year-old boys, a sharp increase in the daily excretion of the glucocorticoid metabolites accompanied by a substantial decrease in the age-related noradrenaline excretion values and the sex hormone metabolite values at an age of 15 years was observed. In the girls, these values varied within the age range, which indicates a more perfect character of the neuroendocrine regulation of their physiological functions in the period of sexual maturation.     

Prepubertal Asians have less limb skeletal muscle.

Skeletal muscle mass in prepubertal Asian children has not been examined previously. The aims of this study were to test the hypotheses that 1) prepubertal Asians have less appendicular skeletal muscle (ASM) mass compared with African-Americans and Caucasians, and 2) ASM is less in prepubertal Asian girls compared with Asian boys. ASM was estimated by using dual-energy X-ray absorptiometry in healthy prepubertal girls (n = 170) and boys (n = 166). The results showed that, after adjusting for age, height, and body weight, 1) Asian girls and boys had less amounts of ASM than African-Americans (P < 0.001); 2) Asian girls had less amounts of ASM than Caucasian girls (P = 0.004); 3) there was a trend towards less ASM in Asian compared with Caucasian boys (P = 0.07); 4) and Asian girls had significantly less ASM than Asian boys (P < 0.001). This study indicates that skeletal muscle mass as a fraction of body weight is smaller in Asian compared with African-American and Caucasian children.