Background: Loss-of-function of immunoglobulin superfamily member 1 (IGSF1) results in an X-linked syndrome of central hypothyroidism and macroorchidism, variable prolactin deficiency, GH deficiency, increased fat percentage, and delayed puberty testosterone rise despite normal timing of testicular growth.
Methods: We investigated the spatial and temporal expression of IGSF1 at the protein and mRNA levels in fetal, neonatal, and adult Wistar rats, using immunohistochemistry, in situ hybridization, and real-time RT-PCR.
Results: High levels of IGSF1 immunoreactivity are observed in various brain regions, including the hypothalamus, but not to any major extent in neuroendocrine cell populations. In the pituitary gland, IGSF1 is present in the Pit1-cell lineage comprising GH, TSH, and PRL-producing cells, but not in gonadotrophs and corticotrophs. In the testis, IGSF1 is present in Sertoli cells (during stages XIIIVI of the seminiferous epithelium) and Leydig cells. IGSF1 is strongly expressed in hepatocytes of the fetal liver, but decreases rapidly to background levels immediately after birth. In all cases, specificity of IGSF1 protein expression was corroborated by in situ hybridization and real-time RT-PCR for the Igsf1 mRNA.
Conclusion: Our results represent the first comprehensive characterization of the organ specific expression profile of IGSF1 in rats. The expression pattern in the pituitary gland suggests a role for IGSF1 in the regulation of TSH, GH, and prolactin secretion. In contrast, IGSF1 is not expressed in the gonadotrophs, suggesting that the delayed puberty and macroorchidism in IGSF1-deficient patients is not likely caused by gonadotropin deficiency, but rather by a local defect in the testis. This is consistent with our observations that IGSF1 is expressed in Sertoli cells (the number of which determines testicular size) and Leydig cells. The results of our study provide a framework that will facilitate future research on IGSF1 function in relevant cells and tissues.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology