Background: In girls with Idiopathic Central Precocious Puberty (ICPP) concern has been raised by the potential impact of GnRH-analogues (GnRHa) treatment on body weight. We evaluated the effect of GnRHa on Body Mass Index (BMI) in girls with ICPP according to weight status at diagnosis.Methods: One hundred seventeen ICPP girls were divided according to pretreatment weight status in: normal weight (NW), overweight (OW) and obese (OB). BMI at one and two years of treatment was assessed. BMI-SDS of 60 patients who reached adult height (AH) was compared to that of 33 ICPP untreated girls.Results: NW girls significantly increased their baseline BMI-SDS at 1 and 2 years of treatment. OW girls only had a significant increment at one year of treatment while OB girls showed no BMI-SDS change. Patients evaluated at AH (at least four years after GnRHa withdrawal) showed a significant decrease on BMI compared to baseline and a significantly lower BMI than the untreated group.Conclusion: In ICPP girls the BMI increase under GnRHa was inversely related to the pretreatment weight status. In the long term follow-up, no detrimental effect of GnRHa on body weight was observed. BMI-SDS was lower in treated than in untreated girls.

AbstractWe present BV photometry and the results of a search for stellar variability in the Galactic globular cluster M 69. The resulting color–magnitude diagram shows significant contamination by field stars. In our variability search we found 62 variable stars, 54 of which were new discoveries.

The Fourier decomposition program used in our paper contained a small error that affected the calculation of the temperatures as well as the V – I colors inferred for the RRab stars. The temperatures that appear in Table 6 in the published article are slightly overestimated, and the V – I colors underestimated. A corrected version of Table 6 is presented below.

Context: Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Objective: Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Patients: Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. Methods: The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Results: Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild type. After preincubation of wild-type and mutant kp54 in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared with the wild type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Conclusion: Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison with the wild type, suggesting a role for this mutation in the precocious puberty phenotype.

Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R activating mutation was described in central precocious puberty (CPP). To investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. The promoter region and the 3 exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54) and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was pre-incubated in human serum prior to stimulation of the cells. Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild-type. After pre-incubation of wild-type and mutant kp54’s in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared to the wild-type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison to the wild-type, suggesting a role for this mutation in the precocious puberty phenotype.

We present the results of a search for variable stars in the globular cluster NGC 5286, which has recently been suggested to be associated with the Canis Major dwarf spheroidal galaxy. 57 variable stars were detected, only 19 of which had previously been known. Among our detections one finds 52 RR Lyrae (22 RRc and 30 RRab), 4 LPV's, and 1 type II Cepheid of the BL Herculis type. Periods are derived for all of the RR Lyrae as well as the Cepheid, and BV light curves are provided for all the variables. The mean period of the RRab variables is = 0.656 days, and the number fraction of RRc stars is N(c)/N(RR) = 0.42, both consistent with an Oosterhoff II (OoII) type -- thus making NGC 5286 one of the most metal-rich ([Fe/H] = -1.67; Harris 1996) OoII globulars known to date. The minimum period of the \RRab's, namely Pab,min = 0.513 d, while still consistent with an OoII classification, falls towards the short end of the observed Pab,min distribution for OoII globular clusters. As was recently found in the case of the prototypical OoII globular cluster M15 (NGC 7078), the distribution of stars in the Bailey diagram does not strictly conform to the previously reported locus for OoII stars. We provide Fourier decomposition parameters for all of the RR Lyrae stars detected in our survey, and discuss the physical parameters derived therefrom. The values derived for the RRc's are not consistent with those typically found for OoII clusters, which may be due to the cluster's relatively high metallicity -- the latter being confirmed by our Fourier analysis of the ab-type RR Lyrae light curves. We derive for the cluster a revised distance modulus of (m-M)V = 16.04 mag. (ABRIDGED)

We present BV photometry of the Galactic globular cluster NGC 5286, based on 128 V frames and 133 B frames, and covering the entire face of the cluster. Our photometry reaches almost two magnitudes below the turn-off level, and is accordingly suitable for age analysis. Field stars were removed statistically from the cluster's color-magnitude diagram (CMD), and a differential reddening correction applied, thus allowing a precise ridgeline to be calculated. Using the latter, a metallicity of [Fe/H] = - 1.70 +/- 0.05 in the Zinn & West scale, and [Fe/H] = - 1.47 +/- 0.02 in the Carretta & Gratton scale, was derived on the basis of several parameters measured from the red giant branch, in good agreement with the value provided in the Harris catalog. Comparing the NGC 5286 CMD with the latest photometry for M3 by P. B. Stetson, and using VandenBerg isochrones for a suitable chemical composition, we find evidence that NGC 5286 is around 1.7 +/- 0.9 Gyr older than M3. This goes in the right sense to help account for the blue horizontal branch of NGC 5286, for which we provide a measurement of several morphological indicators. If NGC 5286 is a bona fide member of the Canis Major dwarf spheroidal galaxy, as previously suggested, our results imply that the latter's oldest components may be at least as old as the oldest Milky Way globular clusters.

We present a long-term project aimed at completing the census of (bright) variable stars in Galactic globular clusters. While our main aim is to obtain a reliable assessment of the populations of RR Lyrae and type II Cepheid stars in the Galactic globular cluster system, due attention is also being paid to other types of variables, including SX Phoenicis stars, long-period variables, and eclipsing binaries.

Diverse mutations in FSH-receptor (FSHR) gene have been described as possible cause of premature ovarian failure (POF). To investigate the presence of mutations and/or polymorphisms in FSHR gene, DNA from 20 POF, 5 of which were diagnosed as resistant ovary syndrome (ROS), and from 44 controls was isolated from peripheral lymphocytes. The complete coding sequence was analysed by PCR followed by SSCP, direct sequencing or restriction enzyme analysis. No mutations in FSHR gene were identified in the patients studied. The two already described polymorphisms in exon 10, A919G and A2039G, cosegregated in all the homozygous individuals, indicating that FSHR presents two isoforms: Ala307–Ser680 and Thr307–Asn680. OR results suggest that the 919G–2039G allelic variant or the homozygous genotype is not associated to disease risk. In addition, a heterozygous substitution T1022C (Val341Ala) was found in two control subjects. We suggest that mutations in FSHR gene are rare in women with POF in Argentine. Presence of a particular FSHR isoform does not appear to be associated with this disease.

OBJECTIVE: The present study evaluated the hypothesis that pulsatile GH secretion is altered in adolescents with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Thirteen adolescent girls with PCOS (ages 13-19 years) and ten eumenorrheic controls (ages 14-19 years) matched for a range of body mass index (BMI) values underwent blood sampling every 20 min for 12 h overnight. METHODS: Serum concentrations of GH and LH were measured by specific immunofluorometric assays (IFMA). Pulsatile secretion was quantitated by deconvolution analysis and pattern orderliness by the approximate entropy (ApEn) statistic. Fasting serum androstenedione, testosterone, 17-hydroxyprogesterone, estrone, estradiol, insulin and IGF-I concentrations were measured by RIA, GH-binding protein (GHBP) by IFMA and IGF-binding protein (IGFBP)-1 and IGFBP-3 by IRMA. RESULTS: Twelve-hour mean and integrated GH concentrations, the mass of GH secreted per burst, and the GH pulse frequency were not distinguishable in patients with PCOS and controls as a whole. Subanalysis of non-obese (BMI<25 kg/m(2)) PCOS and healthy volunteers disclosed elevated 12-h GH production rates (P=0.03) and integrated serum GH concentrations (P=0.04) in (lean) patients with PCOS. ApEn analysis of the orderliness of GH release showed remarkably more regular GH secretion patterns (lower ApEn of GH release) in girls with PCOS compared with controls (P=0.02). Serum GHBP, IGF-I and IGFBP-3 concentrations were similar in both groups, whether lean or obese. However, IGFBP-1 levels were lower in the combined group of PCOS subjects compared with BMI-matched controls (P<0.05). In volunteers with PCOS, mean (12-h) serum GH concentrations correlated positively with mean serum LH levels (P=0.006). Based on deconvolution analysis, the 12-h production rate and the mass of GH secreted per burst also correlated strongly with the cognate LH measure (both predicted) (P=0.004) in PCOS. Androstenedione levels were also related to the 12-h GH secretion rate (P=0.02). CONCLUSIONS: This study shows that non-obese adolescents with PCOS secrete GH at a higher rate and with more orderly patterns, resembling a male profile. Determining whether this pattern reflects an intrinsic hypothalamic abnormality or is secondary to androgen excess in PCOS will require further studies.