Browsing by Subject "Puberty"

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  • Harjutsalo, Valma; Maric-Bilkan, Christine; Forsblom, Carol; Groop, Per-Henrik; FinnDiane Study Grp (2016)
    Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p <0.0001). A non-linear relationship between the age of menarche and risk of diabetic microvascular complications was found in patients with diabetes onset before menarche, but there was no such association in patients with diabetes onset after menarche. Women with delayed menarche (> mean age+ 2 years) had a 2.30 (95% CI 1.27, 4.17; p <0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age +/- 2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (<mean age-2 years) did not have any effect on this risk. Conclusions/interpretation Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.
  • And, Demir (2015)
    This study was undertaken to assess the feasibility of non-invasive sampling and assay of urinary gonadotropins for clinical evaluation of pubertal development. In the first study, the concentrations of LH and FSH in concurrent serum and first-morning- voided (FMV) urine samples of 820 children (486 boys and 334 girls, age 0-17 years) were determined with time-resolved immunofluorometric assay (IFMA). The detection limit of IFMA was 0.018 IU/L for FSH, 0.015 IU/L for LH and 0.012 IU/L for LHspec. It was possible to measure the low prepubertal LH and FSH concentrations reliably in these samples due to the high sensitivity and low detection limits of IFMA. The correlation between serum and urinary gonadotropin values was high (r=0.751; p <0.001 for FSH and r=0.720; p <0.001 for LH), and the urinary and serum concentrations were close to each other. Correcting urinary gonadotropin concentrations on the basis of urinary density or creatinine did not improve the correlation. Age-related changes in urinary LH and FSH (U-LH and U-FSH) were examined. The concentrations of U-LH and U- FSH decreased from birth until the child was a few months old, after which the upper range of the U-LH levels of girls remained stable at below 0.5 IU/L until age 9 years and of boys below 1.0 IU/L until age 11 years. The upper range of the U-FSH levels of girls remained below 3.0 IU/L until age 10 years and of boys below the same concentration until age 12 years. The median U-LH concentration during the prepubertal period was about 0.06 for girls and 0.07 for boys. For the boys, this figure rose 10- fold by age 11, 40-fold by age 12 and 50-fold by age 13-14. The overall increase in the median U-LH concentrations was 75-fold from 5 to 15 years and 35-fold from Tanner stage G1 to G5. The corresponding figures for girls were 30-fold by age 11, 70-fold by age 12 and 90-fold by age 14; the overall increase in median U-LH concentrations was 90-fold from 5 to 15 years and 40-fold from Tanner stage B1 to B5 times. These finding indicate that the U-LH concentrations of FMV samples obtained from clinically prepubertal children reflect pubertal levels. The age-related changes in U-FSH concentrations were similar for boys and girls; the only difference was that the levels were generally higher for girls, in particular between ages 2 8 years. U-FSH reached a 5-fold level compared to prepubertal levels by the end of the puberty in both sexes. FMV U-LH, U-FSH and their ratios correlated well with the corresponding basal and GnRH-stimulated serum concentrations (P <0.001). Receiver operating characteristic (ROC) curve analyses of urinary and serum LH and FSH concentrations showed that FMV U-LH and U-LH/U-FSH performed equally well as the GnRH test for differentiating early puberty (Tanner 2) from prepuberty (Tanner 1) [area under the curve (AUC) 0.768-0.890 vs. 0.712-0.858]. FMV U-LH and U-LH/U-FSH performed equally well as basal S-LH for predicting a pubertal GnRH test result (AUCs 0.90 0.93). Among the tests studied, only FMV U-LH differentiated the transitions from Tanner stage 1 to 2 and Tanner stage 2 to 3 (p <0.001 for boys and p-0.003 for girls). Again, this corroborates that FMV U-LH is the most reliable tool for evaluation of pubertal development. Therefore, FMV urinary LH determinations, which are non-invasive and, at most, minimally stressful for the child patient, can be used for preliminary diagnostic evaluation of pubertal development. It reduces the need for S-LH determinations and the GnRH stimulation tests, both invasive procedures.
  • Torvik, Fartein Ask; Flato, Martin; McAdams, Tom A.; Colman, Ian; Silventoinen, Karri; Stoltenberg, Camilla (2021)
    Purpose: On average, boys have lower academic achievement than girls. We investigated whether the timing of puberty is associated with academic achievement, and whether later puberty among boys contributes to the sex difference in academic achievement. Method: Examination scores at age 16 were studied among 13,477 British twins participating in the population-based Twins Early Development Study. A pubertal development scale, a height based proxy of growth spurt, and age at menarche were used as indicators of puberty. Associations between puberty, sex, and academic achievement were estimated in phenotypic mediation models and biometric twin models. Results: Earlier puberty was associated with higher academic achievement both in boys and girls. The exception was early age at menarche in girls, which associated with lower academic achievement. More than half of the sex differences in academic achievement could be linked to sex differences in pubertal development, but part of this association appeared to be rooted in prepubertal differences. The biometric twin modelling indicated that the association between puberty and academic achievement was due to shared genetic risk factors. Genetic influences on pubertal development accounted for 7%-8% of the phenotypic variation in academic achievement. Conclusions: Pubertal maturation relates to the examination scores of boys and of girls. This can give genes related to pubertal maturation an influence on outcomes in education and beyond. Sex differences in pubertal maturation can explain parts of the sex difference in academic achievement. Grading students when they are immature may not accurately measure their academic potential. (c) 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY license (
  • Liimatta, Jani; Utriainen, Pauliina; Voutilainen, Raimo; Jääskeläinen, Jarmo (2020)
  • Müller, Linda Helena (Helsingin yliopisto, 2022)
    Puberty initiation is a crucial physiological process in human development. A group of hypothalamic neurons secreting the gonadotropin-releasing hormone (GnRH) and expressing the kisspeptin receptor (KISS1R) plays a key role in launching puberty. Furthermore, cellular KISS1R signaling has been shown to regulate GnRH expression and secretion. Although the in vitro differentiation of human pluripotent stem cells into GnRH-secreting neurons has been successful, it is of high interest to generate KISS1R expressing GnRH neurons. By utilizing the CRISPR activation technology, this study aimed to establish a conditional KISS1R-activation cell line using H9 human embryonic stem cells. Through controlling dCas9VP192 abundance using the Tet-On system combined with the dihydrofolate reductase destabilizing domain, the transcriptional activation of KISS1R was temporally regulated by the addition of two antibiotic drugs - doxycycline and trimethoprim. KISS1R expression was primarily assessed by qPCR and verified by immunocytochemistry and the use of a KISS1R-GFP reporter cell line. The main finding of this study is the achievement of a 6217 ± 2286 fold change in KISS1R transcription by introducing two guide RNAs (N = 3). Nevertheless, leaky gene activation was observed without drug treatment (fold change of 63 ± 51). Concludingly, this study successfully led to the generation of a KISS1R-activation cell line. After further characterization and refinement of the activation protocol, the established cell line will enable to investigate whether KISS1R upregulation modulates in vitro GnRH neuron differentiation, electrophysiology, hormone expression, and secretion in the future. Respective outcomes may lead to advances in understanding and treating pubertal disorders.
  • Suutela, Maria (Helsingin yliopisto, 2019)
    Suomessa lasten kasvua seurataan tiheästi neuvolassa ja kouluterveydenhuollossa. Lasten kasvukäyrät on viimeksi uudistettu vuosina 2010–2011 vastaamaan nykyisiä kasvutietoja ja lasten kehitystä. Kasvukäyristä on mahdollista määrittää murrosikään liittyvän kasvupyrähdyksen ajoittumista. Tiheä kasvun seuranta tarjoaa ainutlaatuiset mahdollisuudet tähän murrosiän kasvun ajoittamiseen. Tässä tutkimuksessa pyritään mallintamaan lasten kasvua polynomifunktion avulla ja määrittämään tästä edelleen murrosikään liittyvän kasvupyrähdyksen ajoittuminen. Aineistona käytetään 40 tyypin 1 diabeetikon sekä 205 lääketieteellisessä mikrobiomi-tutkimuksessa mukana olleen lapsen kasvutietoja. Erityisesti ollaan kiinnostuneita kasvupyrähdyksen alkamisajankohdasta sekä iästä huippukasvunopeuden aikaan. Mitään kultaista standardia murrosikään liittyvän kasvupyrähdyksen ajoittamiseen ei ole, mutta murrosiän ajoittamiseen on aikaisemmin käytetty sekä manuaalista määritystä että matemaattisia malleja. Tässä tutkimuksessa käytetään kahta eriasteista polynomifunktiota kasvukäyrien mallintamiseen. Polynomifunktioita verrataan keskenään sekä kumpaakin funktiota erikseen manuaalisesti tehtyyn määritykseen. Huippukasvunopeuden ajankohdaksi saatiin tytöillä aineistosta ja menetelmästä riippuen 11,53–11,95 vuotta ja pojilla 13,39–13,82 vuotta. Polynomifunktiolla saadut tulokset korreloivat hyvin keskenään. Pojilla polynomifunktioilla ja manuaalisella määrityksellä saatujen tulosten välillä ei ollut tilastollisesti merkitsevää eroa. Tytöillä taas manuaalinen ja polynomifunktiolla tehty määritys eivät korreloineet yhtä hyvin keskenään. Manuaalinen määritys ei kuitenkaan ole aukoton tapa määrittää murrosikään liittyvän kasvun ajoittumista. Polynomifunktiolla tehtävä määritys helpottaisi suurempien aineistojen käsittelyä eikä olisi tekijäriippuvaista. Matemaattista kasvukäyrien mallinnusta voitaisiin tulevaisuudessa hyödyntää esimerkiksi neuvolassa ja kouluterveydenhuollon yhteydessä osana sähköisiä kasvukäyriä.
  • Mobley, Kenyon B.; Aykanat, Tutku; Czorlich, Yann; House, Andrew; Kurko, Johanna; Miettinen, Antti; Moustakas-Verho, Jacqueline; Salgado, Andres; Sinclair-Waters, Marion; Verta, Jukka-Pekka; Primmer, Craig R. (2021)
    Over the past decades, Atlantic salmon (Salmo salar, Salmonidae) has emerged as a model system for sexual maturation research, owing to the high diversity of life history strategies, knowledge of trait genetic architecture, and their high economic value. The aim of this synthesis is to summarize the current state of knowledge concerning maturation in Atlantic salmon, outline knowledge gaps, and provide a roadmap for future work. We summarize the current state of knowledge: 1) maturation in Atlantic salmon takes place over the entire life cycle, starting as early as embryo development, 2) variation in the timing of maturation promotes diversity in life history strategies, 3) ecological and genetic factors influence maturation, 4) maturation processes are sex-specific and may have fitness consequences for each sex, 5) genomic studies have identified large-effect loci that influence maturation, 6) the brain-pituitary-gonadal axis regulates molecular and physiological processes of maturation, 7) maturation is a key component of fisheries, aquaculture, conservation, and management, and 8) climate change, fishing pressure, and other anthropogenic stressors likely have major effects on salmon maturation. In the future, maturation research should focus on a broader diversity of life history stages, including early embryonic development, the marine phase and return migration. We recommend studies combining ecological and genetic approaches will help disentangle the relative contributions of effects in different life history stages to maturation. Functional validation of large-effect loci should reveal how these genes influence maturation. Finally, continued research in maturation will improve our predictions concerning how salmon may adapt to fisheries, climate change, and other future challenges.
  • IMAGEN Consortium; Frere, Pauline Bezivin; Vetter, Nora C.; Artiges, Eric; Penttilä, Jani; Lemaitre, Herve (2020)
    Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders.
  • Laakso, Saila; Viljakainen, Heli; Lipsanen-Nyman, Marita; Turpeinen, Ursula; Ivaska, Kaisa K.; Anand-Ivell, Ravinder; Ivell, Richard; Mäkitie, Outi (2018)
    Background: Previous studies suggest increased risk for hypoandrogenism and fractures in men with obesity. We aimed to describe the effects of severe childhood-onset obesity on the cross talk between metabolic state, testes, and skeleton at late puberty. Methods: A cohort of adolescent and young adult males with severe childhood-onset obesity (n = 21, mean age 18.5 years) and an age-matched control group were assessed for testicular hormones and X-ray absorptiometry-derived bone mass. Results: Current median body mass indexes for the obese and control subjects were 37.4 and 22.9. Severe early-onset obesity manifested with lower free testosterone (median [interquartile range] 244 [194-332] vs. 403 [293-463] pmol/L, p = 0.002). Lower insulin-like 3 (1.02 [0.82-1.23] vs. 1.22 [1.01-1.46] ng/mL, p = 0.045) and lower ratio of testosterone to luteinizing hormone (2.81 [1.96-3.98] vs. 4.10 [3.03-5.83] nmol/IU, p = 0.008) suggested disrupted Leydig cell function. The degree of current obesity inversely correlated with free testosterone (t = -0.516, p = 0.003), which in turn correlated positively with bone area at all measurement sites in males with childhood-onset obesity. Conclusions: Severe childhood-onset obesity is associated with impaired Leydig cell function in young men and lower free testosterone may contribute to impaired skeletal characteristics. (C) 2018 S. Karger AG, Basel
  • Pelkonen, Sari; Holopainen, Elina (2020)
    Toiminnallisten vuotohäiriöiden tavallisin syy on anovulaatio. Sitä esiintyy yleisimmin hedelmällisen iän ääripäissä eli parin vuoden ajan kuukautisten alkamisen jälkeen ja menopaussin siirtymävaiheessa eli perimenopaussissa. Syynä tähän on hypotalamus-aivolisäke-munasarja-akselin toimintahäiriö. Nuorilla taustalla on säätelyn kypsymättömyys ja perimenopaussissa munasarjatoiminnan hiipuminen. Anovulaatiossa progesteronin stabiloiva vaikutus kohdun limakalvon rakenteeseen jää puuttumaan. Vuotohäiriön diagnosointi ja hoito voidaan aloittaa perusterveydenhuollossa. Diagnostiikan kulmakiviä ovat tarkka oire- ja vuotoanamneesi sekä yleisvoinnin tarkistus. Nuorilla ensisijaisena hoitona ovat yhdistelmäehkäisytabletit ja perimenopausaalisilla progestiinivalmisteet. Jos tavanomaisella hormonihoidolla ei saada hoitovastetta, potilas lähetetään erikoissairaanhoitoon. Yleistilaltaan heikko ja aneeminen potilas on syytä lähettää naistentautien päivystykseen.