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Background: Hypothalamic hamartomas (HHs) are congenital lesions composed of neurons and astroglia. Frequently, HHs cause central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty, we used cDNA arrays to compare the gene expression profile of an HH associated with CPP with three HHs not accompanied by sexual precocity., Methods: Global changes in gene expression were detected using Affymetrix arrays. The results were confirmed by semiquantitative PCR, which also served to examine the expression of selected genes in the hypothalamus of female monkeys undergoing puberty., Results: All HHs were associated with seizures. Ten genes whose expression was increased in the HH with CPP were identified. They encode proteins involved in three key cellular processes: transcriptional regulation, cell-cell signaling, and cell adhesiveness. They include IA-1 and MEF2A, two transcription factors required for neuronal development; mGluR1 and VILIP-1, which encode proteins involved in neuronal communication, and TSG-6 that encodes a protein involved in cell adhesiveness. Of these, expression of mGluR1 also increases in the female monkey hypothalamus at puberty., Conclusions: Increased expression of these genes in HHs may be relevant to the ability of some HHs to induce sexual precocity., ((c) 2007 S. Karger AG, Basel)

Under physiological conditions, factors affecting the genetic control of hypothalamic functions are predominant in determining the individual variations in timing of pubertal onset. In pathological conditions, however, these variations can involve different genetic susceptibility and the interaction of environmental factors. The high incidence of precocious puberty in foreign children migrating to Belgium and the detection in their plasma of a long-lasting 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) residue suggest the potential role of environmental endocrine disrupting chemicals in the early onset of puberty. This hypothesis was confirmed by experimental data showing that temporary exposure of immature female rats to DDT in vivo results in early onset of puberty. We compared the gene expression profile of hypothalamic hamartoma associated or not with precocious puberty in order to identify gene networks responsible for both hamartoma-dependent sexual precocity and the onset of normal human puberty. In conclusion, pathological variations in the timing of puberty may provide unique information about the interactions of either environmental conditions or genetic susceptibility with the hypothalamic mechanism controlling the onset of sexual maturation, as shown by examples of precocious puberty following exposure to endocrine disrupters or due to hypothalamic hamartoma., ((c) 2005 S. Karger AG, Basel.)

In this review, studies are described indicating that the increase in pulsatile release of gonadotropin releasing hormone that signals the initiation of puberty requires both changes in transsynaptic communication and the activation of glia-to-neuron signaling pathways. The major players in the transsynaptic control of puberty are neurons that utilize excitatory and inhibitory amino acids as transmitters. Glial cells employ a combination of trophic factors and small cell-cell signaling molecules to regulate neuronal function and thus promote sexual development. A neuron-to-glia signaling pathway mediated by excitatory amino acids serves to coordinate the simultaneous activation of transsynaptic and glia-to-neuron communication required for the advent of sexual maturity., (Copyright 2003 S. Karger AG, Basel)

Insulin is well known for its effects on carbohydrate metabolism, but this hormone also plays an important role in regulating ovarian function. Granulosa, theca and stromal ovarian cells may be affected by insulin deficiency or excess, which may be present in women with type 1 diabetes mellitus (T1D). Recent publications have shown that in spite of intensive insulin therapy, some delay in the age of thelarche, pubarche and menarche is still observed in girls with T1D. In addition, ovarian hyperandrogenism may be observed during late adolescence and an increased prevalence of hirsutism and polycystic ovarian syndrome (PCOS) has been described in adult women with T1D. These endocrine abnormalities may be related to nonphysiologic insulin replacement therapy and to hyperglycemia. This paper reviews the pubertal development and the clinical reproductive abnormalities observed in girls with type 1 diabetes mellitus, and shows that several significant clinical problems, such as pubertal delay, menstrual disturbances and hyperandrogenism which may ultimately lead to the development of PCOS in adulthood, may be observed in some of these patients. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents the author index volume 60 of a 2003 issue of "Hormone Research."

Some adolescents with a history of idiopathic central precocious puberty (ICPP) develop hyperandrogenism. Hypothesis: Luteinizing hormone (LH) hypersecretion could be a common mechanism underlying ICPP and polycystic ovary syndrome. Aim: To explore the GnRH-LH axis in those patients. Design: To compare overnight LH secretion in 7 healthy adolescents (CG) with that in patients with prior ICPP [5 with (CPPA) and 7 without (CPPB) hyperandrogenism]. To analyze daytime LH secretion in those patients. Methods: LH secretion was quantified by immunofluorometry and deconvolution analysis. Results: Nighttime mean LH (international units/liter) was higher in CPPA (6.9 ± 1.5) than in CPPB (3.2 ± 0.4, p < 0.05) and CG (2.9 ± 0.4, p < 0.01). Deconvolution analysis revealed a greater nighttime LH frequency (pulses/hour) both in CPPA (0.91 ± 0.06, p < 0.01) and CPPB (0.74 ± 0.02, p < 0.05) than in CG (0.45 ± 0.07). CPPA patients maintained a higher frequency than CPPB. Pulsatile LH production was greater in CPPA than in CG (50 ± 12 vs. 18 ± 3 IU/l/day, p < 0.01). Daytime mass of LH released per burst and pulsatile production rate were significantly greater in CPPA than in CPPB patients. Conclusions: Hyperandrogenic adolescents with prior ICPP show increased pulsatile LH secretion. Augmentation of LH pulsatility may predispose to or cause hyperandrogenism in some adolescents with a history of precocious puberty. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: To compare the efficacy of goserelin 10.8 mg (Zoladex LA – ZLA) administered 9–12 weekly with 3.6 mg (Zoladex – Z) given monthly in suppressing pubertal development, and effect on body mass index (BMI). Methods: Children with central precocious puberty (CPP) treated with Z (n = 34) or ZLA (n = 28) were studied retrospectively. Pubertal scores and BMI SDS during 24 months’ treatment were compared. Results: To attain adequate pubertal suppression, more patients on ZLA than Z required increase in injection frequency (p = 0.02) and this was so for 7/8 patients with a structural aetiology for CPP on ZLA and 2/8 on Z. A greater proportion of patients on ZLA had BMI >+2 SDS before (p = 0.05), and at 18 and 24 months (p = 0.02 and 0.04). BMI SDS transiently increased during the first 6 months on ZLA (p = 0.04). Conclusion: Both Z and ZLA were effective in suppressing puberty. To achieve adequate suppression, increased injection frequency was more likely with ZLA than Z, and particularly in patients with structural defects. Children with CPP had an elevated BMI at the onset of therapy and ZLA had a transient positive influence on BMI. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The precise neuroendocrine mechanisms underlying activation of hypothalamic-pituitary-gonadal (HPG) axis maturation are elusive. The wide age range of pubertal onset among normal individuals throughout the world may suggest that both genetic and environmental factors modulate the timing of puberty. Early activation of the HPG axis, termed central precocious puberty (CPP), causes psychosocial difficulties and may lead to compromised final height, especially if medical intervention is delayed. Although CPP is considered to be idiopathic in the majority of patients, we have recently reported a 27.5% prevalence of familial cases among 147 patients with idiopathic CPP. Segregation analysis of this cohort suggested an autosomal dominant transmission with incomplete sex-dependent penetrance. Allelic variants of candidate genes that regulate the timing of puberty may cause familial CPP. Detection of these genes will provide a tool for identification of children at risk of developing CPP, enabling early intervention with the aim of preventing its distressing outcomes. [ABSTRACT FROM AUTHOR]

Background/Aims: Limited data are available about spontaneous growth, pubertal growth spurt and the long-term outcome of patients suffering from familial male precocious puberty (FMPP). We report on a boy with FMPP whose growth pattern and pubertal development was studied longitudinally without treatment. Methods: Long-term prospective follow-up without treatment of a 6.2-year-old boy with FMPP having inherited a mutation of the LH receptor gene (A568V) from his father. Results: The pubertal growth spurt was of unusual maximal amplitude (growth rate 12.4 cm/year at the age of 5-6 years) and of extraordinary duration lasting for 5.2 years from age 3.8 to 9.0 years. No deterioration of height potential was observed. Height (174 cm) was within target height range (171 .5-188.5 cm) at age 13 years. No central precocious puberty occurred. Conclusion: FMPP is an experiment of nature demonstrating that the amplitude and duration of the pubertal growth spurt are much more variable than previously described. Furthermore, this case emphasizes that the indication for treatment is highly dependent on intrafamilial and individual factors. [ABSTRACT FROM AUTHOR]

The article presents an index of authors who have contributed to the August 2, 2004 issue of the journal "Hormone Research." Some of the author's listed are L. Adan, P. Adiyarnan, F. Afshar, A. Andersson, L.Salem, P. Casano-Sancho, F. Cipollorie, G. Cirillo, M. Cisternino, R. Civa, F. Cizrneeioglu, P. Clapuyt, A. Clark, A. Casey, M. Caso, T. Della Manna, M. Delveeehio, R. Dernetriadou, F. Dernirel, D. Derkach, P. Deseamps, D. Deviteme, O.B. Eden, T. Edouard, C. Eftychi, S. Ehtisharn, U. Eiholzer, K. Ekström.

Girls and boys who enter puberty before 8 and 9 years of age, respectively (corresponding to about –3 SDS), are arbitrarily considered to need referral for endocrine investigation. A recent report from the Lawson Wilkins Pediatric Endocrine Society suggested that the limit for investigation of girls and boys should be lowered to 7 and 8 years, respectively. For African-American girls, 6 years is the suggested age. This recommendation has been criticized. Although short stature is a common end result of precocious puberty, short- and long-term psychological symptoms may be more important, since several studies have indicated psychopathology in this patient group. Whether this can be prevented by gonadotropin releasing hormone agonist treatment remains to be shown. This review will highlight the psychological aspects of early puberty. In short, aspects other than height should also be evaluated when considering treatment of the early maturing child. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although recombinant techniques have enabled the production of limitless amounts of human growth hormone (GH), and clinical methods for diagnosis and treatment have been greatly enhanced, the mean final heights of children with idiopathic GH deficiency (IGHD) treated with GH remain in the range of –1.3 standard deviation scores (SDS) below normal height. One of the methods used to increase height outcomes is to delay the onset and progression of puberty to allow for a longer ‘pre-pubertal’ growth phase. We reviewed the KIGS (Pharmacia International Growth Database) data of patients with IGHD who had been treated with gonadotropin-releasing hormone agonists (GnRHa) in order to see if a greater gain in height could be achieved by altering the tempo of pubertal maturation. Near-final height data were analysed in 39 adolescents (out of a total of 249) who had received GH + GnRHa therapy and were compared with similar data from 1,893 patients with IGHD treated with GH alone. The total change in height SDS in boys who received GH alone was +1.6, in contrast to +1.1 in GH + GnRHa-treated boys; the total change in height SDS in girls who received GH alone was +1.4 in contrast to +1.1 in girls treated with GH + GnRHa. The near final height SDS in girls treated with GH + GnRHa was 1.0 below the mid-parental target height (MPH), whereas there was only a –0.5 SDS difference in girls treated with GH. Approximation to the MPH did not differ in boys between the two treatment groups. These data suggest that the attainment of a substantial height SDS by manipulating the tempo of puberty is limited, but that optimizing growth during the pre-pubertal phase is a more important factor.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents an index of authors who contributed to volume 58 of "Hormone Research."

Early puberty is frequently observed in adopted children. In various studies, early puberty has been associated with decreased final height. In Europe, studies were undertaken to treat early puberty in adopted children with GnRH agonist. This article reviews the current understanding of early puberty in adopted children, including prevalence, background and treatment options. Data from the European studies are briefly described. Besides auxological aspects, psychological items are addressed as well. Studies on the psychological effect of early puberty in adopted children are reported. Future issues include further study in the mechanism of early puberty in adopted children, evaluation of final height results of the growth studies and quality of life assessments in this specific group of children.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: This study aimed at the evaluation of the subjective experience and long-term behavioral and psychological effects of precocious puberty (PP). Methods: 19 female patients who had been treated with GnRH agonists participated in a semistructured interview and completed two standardized checklists. Their parents completed the Child Behavior Checklist (CBCL). Results: The CBCL yielded significantly elevated Internalizing and Total Behavior Problem scores. An elevated risk was found for patients with short adult stature and a relatively late onset of PP. The latter tended to neuroticism, to accentuation of their physical appearance, and felt significantly more insecure than age-related non-PP girls. Conclusion: Our findings suggest that PP can lead to specific behavioral problems, and that patients with a risk factor may need psychosocial support.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hyperinsulinism and hyperandrogenism have the capacity to increase bone mineral density (BMD) and serum leptin, independently of body fat mass. We therefore assessed lumbar BMD and serum leptin in girls with the sequence of a low birthweight and precocious pubarche (PP) in childhood, in whom hyperinsulinism and hyperandrogenism have been described. Methods: Fifty-two non-obese PP girls were studied (age range 6.9–14.9 years). Serum leptin was also measured in 42 control girls, matched for age, body mass index and pubertal stage. Results: BMD SDS, measured by dual-energy X-ray absorptiometry, was elevated in PP girls compared to the population reference (0.39 ± 0.18 SDS; p = 0.03) and bone age, assessed from hand radiographs, was significantly advanced compared to chronological age (1.2 ± 0.1 years; p < 0.0005). Conclusion: Compared to control girls, PP girls had higher leptin levels for degree of body mass index (PP girls: 9.4 ± 0.6 ng/ml; controls: 7.8 ± 0.6 ng/ml; p = 0.01). In PP girls, serum leptin was inversely related to birthweight (r = –0.32, p = 0.01) and positively related to free androgen index (FAI) (r = 0.71, p < 0.0005). BMD SDS was also inversely related to birthweight (r = –0.26, p < 0.05) and positively related to serum leptin (r = 0.42, p < 0.05), FAI (r = 0.45, p < 0.05) and mean serum insulin during oral glucose tolerance testing (MSI) (r = 0.59, p < 0.0005). In multiple regression, MSI was the strongest determinant of BMD SDS (β = 0.50, p = 0.002). In conclusion, elevated BMD and serum leptin in non-obese PP girls were related to degrees of low birthweight, hyperinsulinism and hyperandrogenism. The characteristic hyperinsulinism of PP girls is proposed to be the key variable in this constellation.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Leptin, the ob gene product, is involved in the regulation of body weight in rodents, primates and humans. It provides a molecular basis for the lipostatic theory of the regulation of energy balance. White adipose tissue and placenta are the main sites of leptin synthesis. There is also evidence of ob gene expression in brown fat. Leptin seems to play a key role in the control of body fat stores by coordinated regulation of feeding behaviour, metabolic rate, autonomic nervous system regulation and body energy balance. Apart from the function of leptin in the central nervous system on the regulation of energy balance, it may well be one of the hormonal factors that signal to the brain the body’s readiness for sexual maturation and reproduction. During late pregnancy and at birth when maternal fat stores have been developed, leptin levels are high. During these developmental stages leptin could be a messenger molecule signalling the adequacy of the fat stores for reproduction and maintenance of pregnancy. At later stages of gestation leptin could signal the expansion of fat stores in order to prepare the expectant mother for the energy requirements of full-term gestation, labour and lactation. Leptin serum concentrations change during pubertal development in rodents, primates and humans. In girls, leptin serum concentrations increase dramatically as pubertal development proceeds. The pubertal rise in leptin levels parallels the increase in body fat mass. In contrast, leptin levels increase shortly before and during the early stages of puberty in boys and decline thereafter. Testosterone has been found to suppress leptin synthesis by adipocytes both in vivo and in vitro. The decline of leptin levels in late puberty in boys accompanies increased androgen production during that time and most likely reflects suppression of leptin by testosterone and a decrease in fat mass and relative increase in muscle mass during late puberty in males. This overview focuses on those topics of leptin research which are of particular interest in reproductive and adolescent medicine.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

An author index for the June 2008 issue of "Hormone Research" is presented.