Biology subjects

Juul, A.

Publications and source records attributed to Juul, A..

3 recordsLinked to original sources

bioRxiv2025

Sex Hormone Binding Globulin Controls Gender Specific Lipolytic Activity in Human Abdominal Subcutaneous Adipocytes

Regulation of lipid metabolism is fundamental for metabolic health, and adipose tissue is a central component in this process. Adipose tissue differs dramatically between women and men with a higher subcutaneous capacity for storage and healthy metabolism in women. Sex hormone-binding globulin (SHBG) contributes to the regulation of circulating sex hormone bioavailability and has been shown to predict risk of metabolic dysfunction. We here investigate the sex-specific relationship of SHBG with metabolic status and adipocyte-dependent lipolysis. We measured serum concentrations of sex hormones, SHBG, fasting glucose and insulin in a cohort of 63 women and 27 men from which adipose biopsies were collected and mature adipocytes were isolated. We found that, in women, high serum SHBG concentrations were strongly associated with low HOMA-IR in vivo, and lower baseline lipolysis but higher responsiveness to isopropanol-induced lipolysis ex vivo. In contrast, no effect of SHBG on the above-mentioned parameters were observed in men. In vitro, cultured adipocytes also increased lipolytic capacity in response to SHBG, but only in the absence of testosterone, suggesting that testosterone inhibits the catecholmine-induced lipolysis of SHBG in adipose tissue. In conclusion, we here define a novel role for SHBG in adipocyte lipolysis. At the same time, our data emphasize sex-dependent differences in adipocyte lipid metabolism, and we propose testosterone binding to SHBG as a driving factor mediating these differences.

physiology↗

bioRxiv2024

X-chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome

Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature Sertoli cells highly expressed XIST and have two X-chromosomes, while the mature Sertoli cells lack XIST expression and have only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lack XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.

genetics↗

bioRxiv2020

Ectopic FGF23 production induces mineral changes, osteogenic transdifferentiation, and cancer associated microcalcifications

Testicular microcalcifications consist of hydroxyapatite and have been associated with an increased risk of testicular germ cell tumors (TGCTs) but are also found in benign cases such as loss-of-function variants in the phosphate-transporter SLC34A2. Here, we show that fibroblast growth factor 23 (FGF23), a regulator of phosphate homeostasis, is expressed in testicular germ cell neoplasia in situ (GCNIS), embryonal carcinoma (EC), and human embryonic stem cells. FGF23 is not glycosylated in TGCTs and therefore cleaved into a C-terminal fragment which competitively antagonizes full-length FGF23. Here, Fgf23 knockout mice presented with marked calcifications in the epididymis, spermatogenic arrest, and focally germ cells expressing the osteoblast marker Osteocalcin (gene name: BGLAP, protein name: Osteocalcin). Moreover, the frequent testicular microcalcifications in mice with no functional androgen receptor and lack of circulating gonadotropins are associated with lower Slc34a2 and higher Bglap/Slc34a1 (protein name: NPT2a) expression compared with wild-type mice. In accordance, human testicular specimens with microcalcifications also have lower SLC34A2 and a subpopulation of germ cells express phosphate-transporter NPT2a, Osteocalcin, and RUNX2 highlighting aberrant local phosphate handling and expression of bone-specific proteins. Mineral disturbance in vitro using calcium or phosphate treatment induced deposition of calcium-phosphate in a spermatogonial cell line and this effect was fully rescued by the mineralization-inhibitor pyrophosphate. In conclusion, testicular microcalcifications arise secondary to local alterations in mineral homeostasis, which in combination with impaired Sertoli cell function and reduced levels of mineralization-inhibitors due to high alkaline phosphatase activity in GCNIS and TGCTs, facilitate osteogenic-like differentiation of testicular cells and deposition of hydroxyapatite.

molecular biology↗