The Journal of clinical endocrinology and metabolism · 2019
Reduced Androgen Receptor Expression in Genital Skin Fibroblasts From Patients With 45,X/46,XY Mosaicism.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hornig Nadine C, Demiri Jeta, Rodens Pascal, Murga Penas Eva Maria, Caliebe Almuth, Eckstein Anne Katrin, Schweikert Hans-Udo, Audi Laura, Hiort Olaf, Werner Ralf, Kulle Alexandra E, Ammerpohl Ole, Holterhus Paul-Martin
Аннотация
CONTEXT: Molecular mechanisms causing the broad phenotypic diversity of external masculinization in individuals with 45,X/46,XY mosaicism are poorly understood.
OBJECTIVE: Analysis of androgen receptor (AR) expression and function as a putative influencing factor for the genital phenotype in patients with 45,X/46,XY mosaicism.
DESIGN: Measurement of AR mRNA expression levels, AR activity [DHT-mediated APOD (apolipoprotein D) induction] and cellular 45,X/46,XY ratios in genital skin fibroblasts from individuals with 45,X/46,XY mosaicism and male reference individuals, and determination of the external virilization scale from individuals with 45,X/46,XY mosaicism.
SETTING: University hospital endocrine research laboratory. Patients or Other Participants: 30 genital skin fibroblast cultures (GFs) from male reference individuals and 15 GFs from individuals with 45,X/46,XY mosaicism.
INTERVENTION: None.
MAIN OUTCOME MEASURES: Determination of AR mRNA expression and AR activity in male reference GFs and 45,X/46,XY GFs and correlation of the obtained data with the cellular 45,X/46,XY ratios and the patients' external virilization scale.
RESULTS: In 6 of 15 45,X/46,XY GFs, AR mRNA expression and AR activity were significantly lower compared with those in the 46,XY reference GFs. In this subgroup of reduced AR mRNA expression, a positive trend was seen between AR mRNA expression and the percentage of XY-positive cells. Furthermore, we found a positive correlation between AR activity and the external virilization scale in the 15 45,X/46,XY GF samples (P = 0.03).
CONCLUSION: Our results suggest that AR expression and AR activity might influence the phenotypic variability seen in patients with 45,X/46,XY mosaicism.
OBJECTIVE: Analysis of androgen receptor (AR) expression and function as a putative influencing factor for the genital phenotype in patients with 45,X/46,XY mosaicism.
DESIGN: Measurement of AR mRNA expression levels, AR activity [DHT-mediated APOD (apolipoprotein D) induction] and cellular 45,X/46,XY ratios in genital skin fibroblasts from individuals with 45,X/46,XY mosaicism and male reference individuals, and determination of the external virilization scale from individuals with 45,X/46,XY mosaicism.
SETTING: University hospital endocrine research laboratory. Patients or Other Participants: 30 genital skin fibroblast cultures (GFs) from male reference individuals and 15 GFs from individuals with 45,X/46,XY mosaicism.
INTERVENTION: None.
MAIN OUTCOME MEASURES: Determination of AR mRNA expression and AR activity in male reference GFs and 45,X/46,XY GFs and correlation of the obtained data with the cellular 45,X/46,XY ratios and the patients' external virilization scale.
RESULTS: In 6 of 15 45,X/46,XY GFs, AR mRNA expression and AR activity were significantly lower compared with those in the 46,XY reference GFs. In this subgroup of reduced AR mRNA expression, a positive trend was seen between AR mRNA expression and the percentage of XY-positive cells. Furthermore, we found a positive correlation between AR activity and the external virilization scale in the 15 45,X/46,XY GF samples (P = 0.03).
CONCLUSION: Our results suggest that AR expression and AR activity might influence the phenotypic variability seen in patients with 45,X/46,XY mosaicism.
Предметные рубрики MeSH
AdolescentApolipoproteins DChild, PreschoolFemaleFibroblastsForeskinGenitaliaGonadal Dysgenesis, MixedHumansIn Situ Hybridization, FluorescenceInfantInfant, NewbornMaleMosaicismPrimary Cell CultureRNA, MessengerReceptors, AndrogenScrotumSex Chromosome Disorders of Sex DevelopmentSkinVulvaYoung Adult