Abstract
ObjectiveInsulin-like factor 3 (INSL3) is produced in the testes and has been proposed as a circulating biomarker of Leydig cell capacity, but remains undescribed in 45,X/46,XY mosaicism. The aim was to examine serum concentrations and gonadal expression of INSL3 in 45,X/46,XY mosaicism.MethodsRetrospectively collected data from medical records, gonadal tissue samples, and prospectively analyzed serum samples from eighteen male patients with 45,X/46,XY mosaicism (one prepubertal, four testosterone-treated, 13 untreated) were included. Biochemical, clinical, and histological outcomes were evaluated according to serum INSL3 concentrations, quantified by LC-MS/MS methodology, and gonadal INSL3 immunohistochemical expression.ResultsSerum INSL3 concentrations spanned from below to above the reference range. In untreated patients, the median serum INSL3 SD score was -0.80 (IQR: -1.65 to 0.55) and no significant difference was observed between INSL3 and testosterone. There was no clear association between serum INSL3 and External Genitalia Score at diagnosis, spontaneous puberty, or sperm concentration. INSL3 and CYP11A1 expression overlapped, except for less pronounced INSL3 expression in areas with severe Leydig cell hyperplasia. No other apparent links between INSL3 expression and histological outcomes were observed.ConclusionsIn this pilot study, serum INSL3 concentrations ranged and seemed independent of other reproductive hormones and clinical features in males with 45,X/46,XY mosaicism. Discordant expression of INSL3 and CYP11A1 may explain low INSL3 and normal testosterone concentrations in some patients. Further studies are needed to elucidate the divergence between serum INSL3 and testosterone and the potential clinical use of INSL3.
Highlights
Insulin-like factor 3 (INSL3) is a testicular peptide hormone produced by Leydig cells, which has been proposed as a new marker of testicular function
Studies have suggested that testosterone and INSL3 provide different information about Leydig cell function in hypogonadal patients [1,2,3] and that INSL3 may play a role in ensuring germ cell survival via paracrine pathways in the seminiferous tubules in male rats [4, 5]
There was no correlation between INSL3 standard deviation (SD) scores later in life and EGS at birth in the untreated, post-pubertal patients (r2 = 0.20, p=0.52, Table 1)
Summary
Insulin-like factor 3 (INSL3) is a testicular peptide hormone produced by Leydig cells, which has been proposed as a new marker of testicular function. Studies have suggested that testosterone and INSL3 provide different information about Leydig cell function in hypogonadal patients [1,2,3] and that INSL3 may play a role in ensuring germ cell survival via paracrine pathways in the seminiferous tubules in male rats [4, 5]. Patients with a 45,X/46,XY mosaic karyotype and male sex of rearing present with varying phenotypes both in terms of clinical findings and gonadal histology. The clinical management of this heterogeneous group of patients can be a challenge in terms of gonadal function, possible need of testosterone treatment, surveillance due to the risk of germ cell malignancy, and impaired fertility potential. A new biomarker of clinical and/or histological outcomes could potentially guide clinical management in these patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
