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LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome

 : Context. Osteocalcin (OCN) is an osteoblast-produced polypeptide, emerging as the core element of the bone-testicular axis toghether with its undercarboxylated form (uOCN), proposed to increase testosterone (Te) levels in healthy men, by binding the Gpcr6a receptor on Leydig cells and modulating...

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Autores principales: Carlomagno, Francesco, Spaziani, Matteo, Aureli, Alessia, Tarantino, Chiara, Tenuta, Marta, Sesti, Franz, Gianfrilli, Daniele, Lenzi, Andrea, Isidori, Andrea M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625813/
http://dx.doi.org/10.1210/jendso/bvac150.1348
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author Carlomagno, Francesco
Spaziani, Matteo
Aureli, Alessia
Tarantino, Chiara
Tenuta, Marta
Sesti, Franz
Gianfrilli, Daniele
Lenzi, Andrea
Isidori, Andrea M
author_facet Carlomagno, Francesco
Spaziani, Matteo
Aureli, Alessia
Tarantino, Chiara
Tenuta, Marta
Sesti, Franz
Gianfrilli, Daniele
Lenzi, Andrea
Isidori, Andrea M
author_sort Carlomagno, Francesco
collection PubMed
description  : Context. Osteocalcin (OCN) is an osteoblast-produced polypeptide, emerging as the core element of the bone-testicular axis toghether with its undercarboxylated form (uOCN), proposed to increase testosterone (Te) levels in healthy men, by binding the Gpcr6a receptor on Leydig cells and modulating the GnRH pulse frequency and amplitude. However little is known with regards to its role in pubertal development and male hypogonadism. OBJECTIVE AND DESIGN: We investigated OCN concentrations in 47,XXY men affected by Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism, in a retrospective longitudinal study between 2007 and 2021 at an academic referral center. PATIENTS AND METHODS: 254 KS subjects, divided into the following groups: 1) pre-pubertal (n = 48, from 1 year of age until Tanner stage II), 2) pubertal (n = 46, Tanner stages II through V, <18 years), and 3) adults (n = 160, Tanner stage V, ≥18 years). All (pre-)pubertal patients were Te-naïve. Adult patients were categorized as: 1) eugonadal (total Te > 10.4 nmol/L; n = 47), 2) hypogonadal (Te < 10.4 nmol/L; n = 39), and 3) receiving testosterone replacement therapy (TRT) (n = 74). Data are presented as means ± SD, were tested with Brown-Forsythe and Welch ANOVA tests for unequal variances, corrected for multiple comparisons (Dunnett T3), and with partial correlations, after bootstrapping on 2000 samples. Main outcomes. Total serum OCN, hypothalamic-pituitary-gonadal (HPG) axis hormones (LH, FSH, total Te, 11β-estradiol, SHBG), and derived indexes. RESULTS: OCN levels varied throughout the life span, with a mean of 85.9±30.4 ng/mL in pre-pubertal infants, peaking at 130. 0±77.2 ng/mL in pubertal children (p = 0.243 vs pre-pubertal) and then declining to 22.9±9. 0 ng/mL in adults (p < 0. 001 vs pre-pubertal and pubertal). In (pre-)pubertal boys no correlation with HPG axis hormones was found. When comparing adult KS, OCN values were highest in eugonadal (26.5±10.4 ng/mL), slightly lower in hypogonadal (24.5±8.1 ng/mL, p = 0.268 vs eugonadal) and significantly lower in TRT subjects (20.4±8. 0 ng/mL, p = 0. 008 vs. eugonadal and = 0. 013 vs. hypogonadal). In adults, OCN correlated with both LH (r = 0.23, p = 0. 017) and FSH levels (r = 0.28, p = 0. 004). These significancies were maintained after the exclusion of subjects on TRT. Surprisingly, adjusting for age and BMI revealed significant inverse correlations with total Te (r = -0.44, p = 0. 004), calculated free Te (r = -0.37, p = 0. 016), the Te/LH (r = -0.40, p = 0. 010) and the calculated free Te/LH ratios (r = -0.33, p = 0. 031). These results were confirmed on a smaller sample with available uOCN levels. CONCLUSIONS: In an experimental model of hypergonadotropic hypogonadism, OCN showed no association with gonadal function during normal pre-puberty and pubertal development. In adults, OCN levels were unexpectedly associated with worse testicular function and a higher degree of HPG stimulation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
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spelling pubmed-96258132022-11-14 LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome Carlomagno, Francesco Spaziani, Matteo Aureli, Alessia Tarantino, Chiara Tenuta, Marta Sesti, Franz Gianfrilli, Daniele Lenzi, Andrea Isidori, Andrea M J Endocr Soc Reproductive Endocrinology  : Context. Osteocalcin (OCN) is an osteoblast-produced polypeptide, emerging as the core element of the bone-testicular axis toghether with its undercarboxylated form (uOCN), proposed to increase testosterone (Te) levels in healthy men, by binding the Gpcr6a receptor on Leydig cells and modulating the GnRH pulse frequency and amplitude. However little is known with regards to its role in pubertal development and male hypogonadism. OBJECTIVE AND DESIGN: We investigated OCN concentrations in 47,XXY men affected by Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism, in a retrospective longitudinal study between 2007 and 2021 at an academic referral center. PATIENTS AND METHODS: 254 KS subjects, divided into the following groups: 1) pre-pubertal (n = 48, from 1 year of age until Tanner stage II), 2) pubertal (n = 46, Tanner stages II through V, <18 years), and 3) adults (n = 160, Tanner stage V, ≥18 years). All (pre-)pubertal patients were Te-naïve. Adult patients were categorized as: 1) eugonadal (total Te > 10.4 nmol/L; n = 47), 2) hypogonadal (Te < 10.4 nmol/L; n = 39), and 3) receiving testosterone replacement therapy (TRT) (n = 74). Data are presented as means ± SD, were tested with Brown-Forsythe and Welch ANOVA tests for unequal variances, corrected for multiple comparisons (Dunnett T3), and with partial correlations, after bootstrapping on 2000 samples. Main outcomes. Total serum OCN, hypothalamic-pituitary-gonadal (HPG) axis hormones (LH, FSH, total Te, 11β-estradiol, SHBG), and derived indexes. RESULTS: OCN levels varied throughout the life span, with a mean of 85.9±30.4 ng/mL in pre-pubertal infants, peaking at 130. 0±77.2 ng/mL in pubertal children (p = 0.243 vs pre-pubertal) and then declining to 22.9±9. 0 ng/mL in adults (p < 0. 001 vs pre-pubertal and pubertal). In (pre-)pubertal boys no correlation with HPG axis hormones was found. When comparing adult KS, OCN values were highest in eugonadal (26.5±10.4 ng/mL), slightly lower in hypogonadal (24.5±8.1 ng/mL, p = 0.268 vs eugonadal) and significantly lower in TRT subjects (20.4±8. 0 ng/mL, p = 0. 008 vs. eugonadal and = 0. 013 vs. hypogonadal). In adults, OCN correlated with both LH (r = 0.23, p = 0. 017) and FSH levels (r = 0.28, p = 0. 004). These significancies were maintained after the exclusion of subjects on TRT. Surprisingly, adjusting for age and BMI revealed significant inverse correlations with total Te (r = -0.44, p = 0. 004), calculated free Te (r = -0.37, p = 0. 016), the Te/LH (r = -0.40, p = 0. 010) and the calculated free Te/LH ratios (r = -0.33, p = 0. 031). These results were confirmed on a smaller sample with available uOCN levels. CONCLUSIONS: In an experimental model of hypergonadotropic hypogonadism, OCN showed no association with gonadal function during normal pre-puberty and pubertal development. In adults, OCN levels were unexpectedly associated with worse testicular function and a higher degree of HPG stimulation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m. Oxford University Press 2022-11-01 /pmc/articles/PMC9625813/ http://dx.doi.org/10.1210/jendso/bvac150.1348 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Reproductive Endocrinology
Carlomagno, Francesco
Spaziani, Matteo
Aureli, Alessia
Tarantino, Chiara
Tenuta, Marta
Sesti, Franz
Gianfrilli, Daniele
Lenzi, Andrea
Isidori, Andrea M
LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome
title LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome
title_full LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome
title_fullStr LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome
title_full_unstemmed LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome
title_short LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome
title_sort lbmon274 total osteocalcin levels are independently associated with worse testicular function and a higher degree of hpg axis activation in klinefelter syndrome
topic Reproductive Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625813/
http://dx.doi.org/10.1210/jendso/bvac150.1348
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