Spatial and temporal expression of immunoglobulin superfamily member 1 (IGSf1) in the rat

Loss-of-function mutations in the immunoglobulin superfamily member 1 ( IGSF1 ) gene cause an X-linked syndrome of central hypothyroidism, macroorchidism, variable prolactin and GH deficiency, delayed pubertal testosterone rise, and obesity. To under-stand the pathophysiology of this syndrome, knowledge on IGSF1’s place in normal development is imperative. Therefore, we investigated spatial and temporal protein and mRNA expression of IGSF1 in rats using immunohistochemistry, real-time quantitative PCR (qPCR), and in situ hybridization. We observed high levels of IGSF1 expression in the brain, specifically the embryonic and adult choroid plexus and hypothalamus (principally in glial cells), and in the pituitary gland (PIT1-lineage of GH, TSH, and PRL-producing cells). IGSF1 is also expressed in the embryonic and adult zona glomerulosa of the adrenal gland, islets of Langerhans of the pancreas, and costameres of the heart and skeletal muscle. IGSF1 is highly expressed in fetal liver, but is absent shortly after birth. In the adult testis, IGSF1 is present in Sertoli cells (epithelial stages XIII-VI), and elongating spermatids (stages X-XII). Specificity of protein expression was corroborated with Igsf1 mRNA expression in all tissues. The expression patterns of IGSF1 in the pituitary gland and testis are consistent with the pituitary hormone deficiencies and macroorchidism observed in patients with IGSF1 deficiency. The expression in the brain, adrenal gland, pancreas, liver, and muscle suggest IGSF1’s function in endocrine physiology might be more extensive than previously considered.

[1]  F. Faucz,et al.  Is IGSF1 involved in human pituitary tumor formation? , 2015, Endocrine-related cancer.

[2]  C. Fekete,et al.  Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. , 2014, Endocrine reviews.

[3]  R. Hennekam,et al.  The IGSF1 deficiency syndrome: characteristics of male and female patients. , 2013, The Journal of clinical endocrinology and metabolism.

[4]  F. Walther,et al.  Agonists of MAS oncogene and angiotensin II type 2 receptors attenuate cardiopulmonary disease in rats with neonatal hyperoxia-induced lung injury. , 2013, American journal of physiology. Lung cellular and molecular physiology.

[5]  J. Veldhuis,et al.  Thyrotropin secretion patterns in health and disease. , 2013, Endocrine reviews.

[6]  Jacqueline K. White,et al.  Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement , 2012, Nature Genetics.

[7]  Allan R. Jones,et al.  An anatomically comprehensive atlas of the adult human brain transcriptome , 2012, Nature.

[8]  L. Persani.  Central Hypothyroidism: Pathogenic, Diagnostic, and Therapeutic Challenges , 2012 .

[9]  M. Geraci,et al.  Identification of growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a novel tumor suppressor in pituitary gonadotrope tumors. , 2011, Endocrinology.

[10]  J. Castle,et al.  Definition, conservation and epigenetics of housekeeping and tissue-enriched genes , 2009, BMC Genomics.

[11]  P. Scheiffele,et al.  An Internal Signal Sequence Directs Intramembrane Proteolysis of a Cellular Immunoglobulin Domain Protein* , 2008, Journal of Biological Chemistry.

[12]  T. Nikolskaya,et al.  A comprehensive functional analysis of tissue specificity of human gene expression , 2008, BMC Biology.

[13]  C. Denef.  Paracrinicity: The Story of 30 Years of Cellular Pituitary Crosstalk , 2007, Journal of neuroendocrinology.

[14]  I. Jackson,et al.  Thyrotropin releasing hormone (TRH) may preserve pancreatic islet cell function: potential role in the treatment of diabetes mellitus. , 2007, Acta bio-medica : Atenei Parmensis.

[15]  S. C. Mendis-Handagama,et al.  Leydig cells, thyroid hormones and steroidogenesis. , 2005, Indian journal of experimental biology.

[16]  H. Aburatani,et al.  Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. , 2005, Genomics.

[17]  E. Fliers,et al.  Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus. , 2005, The Journal of clinical endocrinology and metabolism.

[18]  S. Czirják,et al.  Differential gene expression in pituitary adenomas by oligonucleotide array analysis. , 2005, European journal of endocrinology.

[19]  Rui Li,et al.  An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma , 2005, Oncogene.

[20]  J. Dupont,et al.  Activin and inhibin receptor gene expression in the ewe pituitary throughout the oestrous cycle. , 2004, The Journal of endocrinology.

[21]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  F. Walther,et al.  Gene expression profile and histopathology of experimental bronchopulmonary dysplasia induced by prolonged oxidative stress. , 2004, Free radical biology & medicine.

[23]  K. Burns,et al.  Normal Reproductive Function in InhBP/p120-Deficient Mice , 2003, Molecular and Cellular Biology.

[24]  J. Ervasti.  Costameres: the Achilles' Heel of Herculean Muscle* 210 , 2003, The Journal of Biological Chemistry.

[25]  G. Chiumello,et al.  Thyroid function and puberty. , 2003, Journal of pediatric endocrinology & metabolism : JPEM.

[26]  A. Orth,et al.  Large-scale analysis of the human and mouse transcriptomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[28]  D. Bernard,et al.  Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle. , 2001, Molecular endocrinology.

[29]  T. Woodruff,et al.  Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP). , 2001, Molecular endocrinology.

[30]  D. Bernard,et al.  Structure and expression of a membrane component of the inhibin receptor system. , 2000, Endocrinology.

[31]  P. Allavena,et al.  Identification and genomic organization of a gene coding for a new member of the cell adhesion molecule family mapping to Xq25. , 1998, Gene.

[32]  U. Hilbers,et al.  Neuroendocrine properties of adrenocortical cells. , 1998, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[33]  R. Mazzarella,et al.  Cloning and expression of an immunoglobulin superfamily gene (IGSF1) in Xq25. , 1998, Genomics.

[34]  M. Taketo,et al.  Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Pawlikowski,et al.  Effects of TRH and TRH-like peptide pGLU-HIS-GLY-NH2 on adrenocortical cell proliferation in rats , 1996, Endocrine.

[36]  M. Gratzl,et al.  Neural cell adhesion molecules in rat endocrine tissues and tumor cells: distribution and molecular analysis. , 1993, Endocrinology.

[37]  P. Chatelain,et al.  The paracrine role of Sertoli cells on Leydig cell function , 1992, Cell Biology and Toxicology.

[38]  M. Rosenfeld,et al.  Alternative translation initiation site usage results in two structurally distinct forms of Pit-1. , 1991, The Journal of biological chemistry.

[39]  W. Schulze,et al.  A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell. , 1990, The American journal of anatomy.

[40]  P. Malfertheiner,et al.  Effects of TRH on Pancreatic Growth and Secretion in Rats , 1990, Pancreas.

[41]  H. Kawano,et al.  Location of thyrotropin-releasing hormone-like immunoreactivity in rat pancreas. , 1983, Endocrinology.

[42]  M. Parvinen.  Regulation of the seminiferous epithelium. , 1982, Endocrine reviews.

[43]  K. Toshimori.  Sperm-Head Formation and Factors Affecting It , 2009 .

[44]  J. Wilber,et al.  Localization of thyrotropin-releasing hormone mRNA expression in the rat heart by in situ hybridization histochemistry. , 1996, Pathobiology (Basel).