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Male acceleration of puberty in female mice (Mus musculus).

Nine experiments were performed to investigate various aspects of the acceleration of puberty in female house mice produced by the presence of a male mouse or urine from males. The findings include the following: (a) Grouping males has no effect on the urinary chemosignal that accelerates puberty except that (b) urine from dominant males produces greater acceleration than urine from subordinates. (c) Young female mice must be exposed to the male urine for at least 2-3 hr/day or to the presence of a male for 1 hr/day to produce acceleration of first vaginal estrus. (d) Females are accelerated to the same extent in attaining puberty whether treated with urine from the same male or a different male each day. (e) Urine from the father or a full brother, or the presence of those close relatives, exerts no differential acceleratory or retarding effect on puberty when compared with urine from or the presence of unrelated males. (f) Excreted or bladder urine from adrenalectomized males accelerates puberty to the same extent as urine from intact males, but (g) the presence of an adrenalectomized male does not produce the same degree of acceleration that occurs when an intact male is present. (h) Behavioral observations indicate that adrenalectomized males pursue young females less and attempt fewer mounts during a brief test period. Together, these findings have some important consequences with respect to our understanding of both the mechanisms of acceleration of puberty in the house mouse and the population and reproductive biology of these mice.

Adrenal Cortex Hormones↗

Breast contact thermography for differentiation between premature thelarche and true precocious puberty.

Breast contact thermography was used to differentiate between premature thelarche and true precocious puberty. The technique was applied to 10 girls with premature thelarche, 12 with precocious puberty and 105 controls (Tanner B1-5). In controls, the scores attributed to the maturative thermographic signs correlated with breast development stages. In premature thelarche thermographic signs of vascularization were always absent, while in precocious puberty they were always observed, although in some cases unilaterally. The thermographic index (higher total score between the two breasts) ranged from 0 to 3 in girls with premature thelarche and from 4 to 10 in girls with precocious puberty. The thermographic pattern in premature thelarche was similar to that in prepubertal girls and did not progress in two girls who were repeatedly examined. We emphasize the useful role of contact thermography in evaluating pubertal breast development and in differentiating between premature thelarche and true precocious puberty.

Age Determination by Skeleton↗

The role of Doppler evaluation of the uterine artery in girls around puberty.

BACKGROUND: Presently, the only sonographic parameters used to follow puberty in girls are size and morphology of the uterus and ovaries. Doppler of the uterine artery appears a useful complementary parameter to follow puberty. OBJECTIVE: To determine the potential contribution of Doppler evaluation of the uterine artery in girls around puberty. MATERIALS AND METHODS: We investigated 61 healthy female volunteers aged 2-15 years (mean 10.3 years). In each girl we performed a standard pelvic transabdominal US examination, including measurement of the uterus and ovaries. Uterine arteries were visualized by colour Doppler and a pulsed signal was obtained in each patient. The blood flow velocity waveform was analysed and the pulsatility index (PI) was calculated. Growth of the uterus and ovaries was plotted against age, and the PI was compared to each of the other studied variables (age, size of uterus, volume of ovaries). RESULTS: We observed a strong negative correlation between the PI of the uterine artery and the usually studied variables. We also observed a progressive modification of the Doppler signal pattern of the uterine artery during the establishment of puberty: the narrow systolic flow waves found in prepubertal girls were progressively replaced by a systolic-diastolic flow wave. CONCLUSIONS: The demonstration of diastolic flow can confirm the onset of puberty.

Adolescent↗

Assessment of the effects of intensive training of community based staff in the screening of children for disorders of growth and puberty.

INTRODUCTION: The effects of an intensive training programme involving screening of children for disorders of growth and puberty for community based nursing and medical staff employed by Cardiff Community Healthcare NHS Trust were audited to assess the impact of this training on referrals to the local hospital based growth clinic. METHOD: Referrals from community based staff to the growth clinic of patients living in the geographical area in which staff underwent training were compared with those from general practitioners in the 18 months prior to and following the training programme. Hospital notes were available for 209 of 254 (82.2%) patients identified. We excluded 112 referrals as they did not have a problem relating to growth or puberty or were inter-hospital referrals. Hence 97 referrals were included in the final audit. RESULTS: Forty referrals occurred prior to compared with 57 following the training programme. The number of referrals from community based staff increased threefold during the six months immediately following the training programme but then returned to the previous level. There were no differences in age or height standard deviation scores at referral between groups at any time. The proportion of children referred from the community with significant abnormalities of growth or puberty (for example, hypothyroidism or precocious puberty) increased from two of 15 referrals to six of 30 referrals following the training programme. CONCLUSIONS: Intensive training in screening for disorders of growth and puberty can increase the number of referrals of children with significant pathology but at the cost of increased total number of referrals. The increase in referrals is not sustained with time, suggesting continued training is necessary.

Adolescent↗

Puberty in chronically diseased patients.

Delayed onset of puberty and a reduced pubertal growth spurt are often reported in patients suffering from chronic diseases. The basis of abnormal puberty in these patients is multifactorial. Nutritional deficiency may contribute to growth disorders and delayed puberty. Insufficient food supply and/or eating disorders and/or malabsorption of nutrients can be observed in these patients. Moreover, increased energy supplies are often needed in patients with chronic lung disease, infection or inflammation. More specific factors due to the disease itself may be involved in growth and puberty disorders. Abnormalities of the growth hormone (GH)-insulin-like growth factor (IGF)1 axis and gonadotrophin secretion have been described in patients with chronic renal failure, cystic fibrosis and Crohn's disease. More recently, it has been shown that cytokines produced during chronic diseases such as juvenile idiopathic arthritis may affect the GH-IGF1 axis. Finally, concomitant medication, namely corticosteroids, which are often given to these patients, may contribute to delayed puberty and poor pubertal growth.

Adolescent↗

The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration.

During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European countries. These observations are raising the issues of current differences and secular trends in timing of puberty in relation to ethnic, geographical, and socioeconomic background. None of these factors provide an unequivocal explanation for the earlier onset of puberty seen in the United States. In the formerly deprived migrating children, refeeding and catch-up growth may prime maturation. However, precocious puberty is seen also in some nondeprived migrating children. Attention has been paid to the changing milieu after migration, and recently, the possible role of endocrine- disrupting chemicals from the environment has been considered. These observations urge further study of the onset of puberty as a possible sensitive and early marker of the interactions between environmental conditions and genetic susceptibility that can influence physiological and pathological processes.

Age Factors↗

High serum allopregnanolone levels in girls with precocious puberty.

Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P < 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values. In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.

Adrenocorticotropic Hormone↗

Optimal therapy of pubertal disorders in precocious/early puberty.

GnRHa have been used in the treatment of central precocious puberty (CPP) for a decade and some final results of this therapy are now available. Treatment preserves height potential in younger patients and a complete recovery of the hypothalamic-pituitary-gonadal axis occurs at the end of treatment. However, some aspects of the management of CPP are still debated. Probably the age limits between normal and precocious puberty have to be lowered, and new diagnostic tools will modify and simplify diagnostic criteria. The possibility of progression of premature thelarche into precocious puberty, the pathogenesis of organic and idiopathic precocious puberty, the criteria for decision to treat and to stop treatment and the utility of an association with GH treatment will be better understood in the future. Follow-up of patients after stopping therapy includes frequency and characteristics of menses, the possible higher incidence of polycystic ovary-like syndrome and the correct achievement of a normal peak bone mass and body composition. In this review we discuss some of these points, with particular attention to precocious puberty in girls.

Adolescent↗

Disorders of puberty: inactivating and activating molecular mutations.

Recent developments have increased our understanding of the molecular mechanisms that are responsible for several disorders of puberty. Specific gene mutations have been identified in three syndromes, one that is associated with delayed puberty (Kallmann syndrome) and two that are associated with precocious puberty (McCune-Albright syndrome and familial male precocious puberty). Mutations in the KAL gene have been shown to be responsible for cases of X-linked Kallmann syndrome. This gene encodes a protein that is believed to be involved in neural target recognition and protease inhibition. In McCune-Albright syndrome, heterozygous, postzygotic somatic mutations of the alpha-subunit of the stimulatory guanine nucleotide binding protein Gs have been shown to stimulate constitutive G protein activation and long-term cyclic adenosine monophosphate production. Similarly, familial male precocious puberty has been linked to gain-in-function mutations that result in increased levels of cyclic adenosine monophosphate; however, these mutations are found in the luteinizing hormone receptor gene itself. The clinical manifestations and the recent molecular advances in each of these three syndromes are explored.

Cyclic AMP↗

Precocious puberty following severe head trauma.

True precocious puberty is frequently secondary to intrinsic central nervous system pathology, but is rare following external head trauma. We describe two children who developed precocious puberty within three months of severe exogenous head trauma. Infusion of luteinizing hormone releasing factor induced a prompt rise in circulating gonadotropin concentrations and established that their sexual precocity was the result of premature activation of the hypothalamic-pituitary axis. While the precise mechanism by which exogenous head trauma causes precocious puberty remains unknown, the clinical features of these children's disorders are consistent with the hypothesis that extra-hypothalamic areas restrain pituitary gonadotropin secretion before puberty and that damage to these areas can result in precocious puberty.

Child↗

The effect of prolonged administration of an anabolic steroid (oxandrolone) on growth in boys with constitutionally delayed growth and puberty.

UNLABELLED: Short-term oxandrolone treatment is used to stimulate growth in boys with constitutional delay of growth and puberty (CDGP). Oxandrolone stimulates growth, but a beneficial effect on final height has not been established. In our study, we report the effect of long-term treatment (30-57 months) with oxandrolone in 18 boys with CDGP, compared with nine puberty-matched, untreated controls (group 1). The oxandrolone-treated boys were divided into two groups: four boys who received oxandrolone before onset of puberty (group 2), and 14 boys who started oxandrolone therapy during Tanner stage 2 (group 3). Height standard deviation scores for calender age (HSDSCA) between the three groups of patients at Tanner stage 2 (G2) were not different: -2.86 (SD 0.56) in the controls and -2.60 (SD 0.52) in group 2 and -2.81 (SD 0.59) in group 3. Age at G2 was 15.1 (SD 1.4) years (controls), 14.6 (SD 0.5) years (group 2) and 14.0 (SD 0.9) years (group 3). Height velocity in the time span from G2 to G5 was more pronounced in the oxandrolone-treated boys: 7.7 (SD 0.5) cm/year in group 2 and 7.7 (SD 1.4) cm/year in group 3 versus 5.1 (SD 0.9) cm/year in the controls. Height gain was significantly increased in the oxandrolone treated groups: 25.8 (SD 3.8) in group 2 and 25.2 (SD 3.7) in group 3 versus 19.8 (SD 4.9) in the controls (P < 0.05). Final height did not differ significantly among the three groups: 168.5 (SD 7.0) cm in the controls and 173.0 (SD 4.0) cm in group 2 and 167.8 (SD 5.3) cm in group 3. HSDSCA increased during puberty in all three groups. At final height, HSDSCA (calculated at age = 20 years) was -2.01 (SD 1.05), -1.34 (SD 0.59) and -2.12 (SD 0.79) respectively in groups 1, 2 and 3. An effect of oxandrolone on HSDSCA was not found. Target height was neither reached by the controls nor by the treated groups. Tempo of pubertal development was not different in the three groups, and delta BA/delta CA did not alter after start of oxandrolone treatment in groups 2 and 3. CONCLUSION: Boys with CDGP may benefit from oxandrolone treatment in terms of increased height gain. Starting treatment before the onset of puberty may be favourable.

Adolescent↗

Persistent microalbuminuria in adolescents with type I (insulin-dependent) diabetes mellitus is associated to early rather than late puberty. Results of a prospective longitudinal study.

Microalbuminuria is generally accepted to be highly predictive of overt diabetic nephropathy which is the leading cause of end-stage renal failure and, consequently, of death in patients with type 1 (insulin-dependent) diabetes mellitus (IDDM). Its early identification and therapy are exceedingly important. We studied prospectively the occurrence of microalbuminuria (MA) in relation to puberty and its pubertal stages in 164 children and adolescent patients (83 girls and 81 boys) with IDDM. Analysing 100 healthy subjects, normal values for albumin excretion (range: 0-10.1 micrograms/min/1.73 m2) according to sex and the different pubertal stages were defined. No significant difference between the groups were noted and, therefore, 20 micrograms/min per 1.73 m2 (3 SD above the mean) was generally defined as cutoff for MA. Of the patients with IDDM studied, 20% (20 females and 12 males) developed persistent MA (22.1-448.2 micrograms/min/1.73 m2) during the study period of 8 years. The first manifestation of persistent MA was in 69% (13 females and 9 males) during stages of early and midpuberty; and in 28% (6 females and 3 males) at a late pubertal stage or at the end of puberty. The only child who developed MA before the onset of puberty (range: 23.5-157.4 micrograms/min/1.73 m2) was found to have dystopic kidney. Therefore, all patients with IDDM should be screened for MA regardless of diabetes duration, sex and level of diabetes control beginning at the very first stage of puberty and neither earlier nor after puberty as suggested by the American Diabetes Association.

Adolescent↗

Urinary markers of bone turnover in healthy children and adolescents: age-related changes and effect of puberty.

During growth, bones change their dimensions rapidly with the changes involving both formation and resorption processes. Small cross-linked peptides coming from type I collagen molecules are excreted in urine when bone is resorbed. To date, conflicting results have been presented concerning the age- and puberty-related changes of urinary markers. The purpose of the present study was to verify the effect of age, gender, and puberty on the urinary excretion of type I collagen degradation products in healthy children and adolescents. Timed spot urines from 176 children (4-20 years old) and 50 young adults were analyzed. The concentrations of N-telopeptides of type I collagen (NTx), pyridinolines (Pyr), and deoxypyridinolines (Dpyr) were measured, and the results were normalized to creatinine. Age-related changes in cross-links excretion were observed. The levels decreased with age, and a peak of excretion was shown at the beginning of adolescence. Prepubertal levels of all the markers were four- to five-fold higher than in adults, and they decreased towards adult levels in late puberty. Girls had significantly higher levels of all biochemical markers than boys at pubertal stage 2. We also observed a remarkable effect of puberty on the levels of bone degradation products that was independent of age and gender. Our results indicate that bone resorption is high in children relative to that in adults, and that urinary levels of NTx, Pyr, and Dpyr change as a function of age, gender, and puberty.

Adolescent↗

Longitudinal changes in body composition, physical capacities and energy expenditure in boys and girls during the onset of puberty.

BACKGROUND: The onset of puberty is a period of rapid anatomical and physiological alterations expected to induce changes in metabolic rate and energy requirements of children. AIM OF THE STUDY: To evaluate the changes in anthropometrical features, body composition, physical capacities, and energy expenditure (EE) of boys and girls during the period of onset of puberty. METHODS: Sixteen children (8 boys and 8 girls were recruited in the same school-class and studied both at 10.4 and 12.8 years of age. Body composition was assessed by bioimpedance analysis. Peak oxygen uptake (peak VO2) was measured using an automated on-line system during exercising on a cycle ergometer. Energy expenditure (EE) was determined by whole-body indirect calorimetry over a 24-h period after a 12-h period of adaptation to the calorimeters. Volunteers followed the same activity programme that included four 15-min periods of exercise. RESULTS: During the onset of puberty, boys and girls gained 4.7 +/- 2.1 kg x y(-1) (P < 0.0003) fat-free mass (FFM), whereas fat mass gain was 1.0 +/- 1.2 kg x y(-1) (P < 0.05) in girls and 0.20 +/- 0.66 kg x y(-1) in boys (NS). Peak VO2 adjusted for differences in FFM was not significantly affected by gender or pubertal stage. However, adjusted external mechanical power performed at peak VO2 was higher in pubertal than in prepubertal children, by 40% (P < 0.0001) and 22% (P < 0.003) in boys and girls, respectively. It was also 17% (P < 0.0002) higher in pubertal boys than in pubertal girls. Daily and sleeping EE increased by 38% and 32% in boys and girls, respectively, during the 2.4-y period (P< 0.0001). Adjusted EEs were also significantly higher in pubertal than in prepubertal boys (P< 0.05 and P< 0.003), but not in girls. The main significant determinants of daily EE were FFM (r2 = 0.866, P < 0.0001), peak VO2 (r2 = 0.017, P < 0.04), and age (r2 = 0.014, P < 0.05). Tanner's stage was an additional determinant of sleeping EE (r2 = 0.025, P < 0.006). CONCLUSIONS: The increases in physical capacities and EE during the onset of puberty indicated clear gender differences, which could be explained mainly by alterations of body composition in boys and girls, and by changes in hormonal status in boys. They also stressed the significant increase in energy requirements of children, especially boys, at an early stage of puberty.

Adipose Tissue↗

Marked changes of lipid levels during puberty in a patient with lipoprotein lipase deficiency.

UNLABELLED: Clinical and biochemical characteristics of a female patient with familial lipoprotein lipase deficiency have been followed in short intervals before and during puberty. The proband is compound heterozygote for two missense mutations in the lipoprotein lipase gene. One mutation occurs in codon 250 (Asp250-->Asn), the other is in codon 410 (Glu410-->Lys). The residual lipoprotein lipase activity in the proband is less than 10% of controls. Before puberty the proband usually presented with moderate isolated hypertriglyceridaemia. During the initial phase of puberty a dramatic increase in the plasma concentration of both cholesterol and triglycerides was observed. During the second half of puberty a reduction of cholesterol but not of triglycerides was noticed. CONCLUSION: These findings show that the phenotypic expression of familial chylomicronaemia can be modified to a large extent by hormones. Furthermore they demonstrate the need for a closer clinical observation of type I patients during puberty.

Adolescent↗

Bone mineral density during puberty in western Canadian children.

To assess the influence of puberty and its associated changes in body weight and height on bone mineral density (BMD), lumbar spine (L2-L4) and femoral neck BMD were measured in 74 healthy, active children (9-16 years) using dual-photon absorptiometry. Competitive swimmers were recruited to minimize the potential effect variability in mechanical loading regime may have on bone density of the lumbar spine. Tanner staging was used to assess stage of puberty. Current dietary calcium intake was assessed by analysis of 6-day dietary records. Significant differences in spinal and femoral neck BMD occurred between early (Tanner 1 and 2) and late stages of puberty (Tanner 4 and 5), P < 0.05. A significant correlation was found between bone density and dietary calcium intake. However stepwise regression analyses demonstrated stage of puberty or body weight were the only factors which significantly affected spinal BMD, accounting for 77% and 68% of the variability respectively; while at the femoral neck, body weight accounted for 52% of the variability. These results demonstrate that when potential interacting factors are controlled for through regression analyses, differences in BMD occur mainly as a function of puberty and the associated gains in body weight.

Adolescent↗

Pubertal evaluation of adolescent boys with beta-thalassemia major and delayed puberty.

OBJECTIVE: To examine the hormonal status of the hypothalamic-pituitary-gonadal axis in adolescent males with beta-thalassemia major. DESIGN: Controlled clinical study. SETTING: Tertiary referral teaching hospital. PATIENT(S): Thirty-three adolescent males with beta-thalassemia major. INTERVENTION(S): Basal LH, FSH, and T were examined. All individuals received 100 microg GnRH analogue. Four hours later the hormone levels were retested. Patients with beta-thalassemia and low T levels received hCG. MAIN OUTCOME MEASURE(S): The preintervention and postintervention levels of FSH, LH, and T were examined. RESULT(S): Of the 33 beta-thalassemia major adolescents, 17 had delayed puberty. The difference in basal LH, FSH, and T levels between delayed and normal puberty beta-thalassemia groups were statistically significant. These levels were significantly lower compared with the constitutional delayed puberty group and become even more significant after GnRH analogue administration. The T levels in the beta-thalassemia group were significantly lower than in the control group. After hCG administration, the T levels remained significantly lower in the delayed-puberty beta-thalassemia compared to the normal-puberty beta-thalassemia group. CONCLUSION(S): Despite recent therapeutic advances in the management of beta-thalassemia major, the risk of secondary endocrine dysfunction remains high. Hypogonadism is one of the most frequent endocrine complications.

Adolescent↗

Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty.

OBJECTIVE: To determine longitudinal changes in insulin sensitivity (SI), insulin secretion, and beta-cell function during puberty in white and black youth. STUDY DESIGN: The tolbutamide-modified frequently sampled intravenous glucose tolerance test and minimal modeling were used to measure SI, the acute insulin response to glucose (AIRg), and beta-cell function (disposition index, DI) in white (n = 46) and black (n = 46) children (mean [+/-SD] age at baseline = 10.2 +/- 1.7 years). Growth curve models (including 272 observations) with SI, AIRg, and DI regressed on Tanner stage were run after adjusting for covariates. RESULTS: After adjusting for covariates, growth curve models revealed that SI decreased and subsequently recovered by the end of puberty in whites and blacks (both p < .05), AIRg decreased linearly across Tanner stages in both races (both p < .001), and DI decreased across puberty in blacks (p = .001) but not in whites (p = .2). CONCLUSIONS: White and black youth exhibited transient insulin resistance and diminished AIRg during puberty. The progressive decline in DI among blacks versus whites may reflect a unique effect of puberty on beta-cell compensation in blacks. Future studies are needed to identify whether this difference contributes to the increased risk of type II diabetes in young blacks.

Black or African American↗