From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function

被引:23
作者
Bernard, Daniel J. [1 ,2 ]
Brule, Emilie [2 ]
Smith, Courtney L. [1 ]
Joustra, Sjoerd D. [3 ]
Wit, Jan M. [3 ]
机构
[1] McGill Univ, Dept Pharmacol & Therapeut, 3655 Promenade Sir William Osler, Montreal, PQ H3G 1Y6, Canada
[2] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 0C7, Canada
[3] Leiden Univ, Med Ctr, Dept Pediat, NL-2333 ZA Leiden, Netherlands
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
central hypothyroidism; IGSF1; mutation; pituitary; TRH;
D O I
10.1210/js.2017-00478
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein highly expressed in the mammalian pituitary gland. Shortly after its discovery in 1998, the protein was proposed to function as a coreceptor for inhibins (and was even temporarily renamed inhibin binding protein). However, subsequent investigations, both in vitro and in vivo, failed to support a role for IGSF1 in inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next-generation sequencing identified mutations in the X-linked IGSF1 gene in boys and men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. Investigations in two Igsf1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain unresolved. Moreover, IGSF1 mutations are also commonly associated with other clinical phenotypes, including prolactin and growth hormone dysregulation, and macroorchidism. How the loss of IGSF1 produces these characteristics is unknown. Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1's function in endocrine tissues, including the pituitary and testes. Copyright (c) 2018 Endocrine Society
引用
收藏
页码:220 / 231
页数:12
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