ArticleScientific reports2017
The syndrome of central hypothyroidism and macroorchidism: IGSF1 controls TRHR and FSHB expression by differential modulation of pituitary TGFβ and Activin pathways.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- "Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)-Part-1".Journal of endocrinological investigation · 2025Guideline
- Identification of a Novel Nonsense Mutation in theChildren (Basel, Switzerland) · 2025Article
- A Novel De Novo Nonsense Pathogenic Variant inJCEM case reports · 2025Article
- X-Linked Gene Dosage and SOX2 Act as Key Roadblocks for Human Germ Cell Specification in Klinefelter Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation.Nature communications · 2024Article
- Diagnosing and treating anterior pituitary hormone deficiency in pediatric patients.Reviews in endocrine & metabolic disorders · 2024Review
- Hypothalamic hormone deficiency enables physiological anorexia.bioRxiv : the preprint server for biology · 2024Article
- Rare case of central congenital hypothyroidism due to aBMJ case reports · 2023Article
- Chromosome-Level Analysis of theBiology · 2023Article
- Enhancer hijacking at the ARHGAP36 locus is associated with connective tissue to bone transformation.Nature communications · 2023Article
- The extant immunoglobulin superfamily, member 1 gene results from an ancestral gene duplication in eutherian mammals.PloS one · 2022Article
- The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular GrowthJournal of clinical research in pediatric endocrinology · 2021Article
- IGSF1 Does Not Regulate Spermatogenesis or Modify FSH Synthesis in Response to Inhibins or Activins.Journal of the Endocrine Society · 2021Article
- Combined use of thyroid stimulating hormone plus free thyroxine levels and gestational age at birth for the prediction of neonatal hypothyroidism and associated risk factors.Experimental and therapeutic medicine · 2020Article
- Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due toJournal of clinical research in pediatric endocrinology · 2020Article
- Age-related gene and miRNA expression changes in airways of healthy individuals.Scientific reports · 2019Article
- Recent advances in research on isolated congenital central hypothyroidism.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2019Article
- A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome.Clinical endocrinology · 2018Article
- From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function.Journal of the Endocrine Society · 2018Review
- Two siblings with congenital central hypothyroidism caused by a novel mutation in theClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IGSF1 (Immunoglobulin Superfamily 1) gene defects cause central hypothyroidism and macroorchidism. However, the pathogenic mechanisms of the disease remain unclear. Based on a patient with a full deletion of IGSF1 clinically followed from neonate to adulthood, we investigated a common pituitary origin for hypothyroidism and macroorchidism, and the role of IGSF1 as regulator of pituitary hormone secretion. The patient showed congenital central hypothyroidism with reduced TSH biopotency, over-secretion of FSH at neonatal minipuberty and macroorchidism from 3 years of age. His markedly elevated inhibin B was unable to inhibit FSH secretion, indicating a status of pituitary inhibin B resistance. We show here that IGSF1 is expressed both in thyrotropes and gonadotropes of the pituitary and in Leydig and germ cells in the testes, but at very low levels in Sertoli cells. Furthermore, IGSF1 stimulates transcription of the thyrotropin-releasing hormone receptor (TRHR) by negative modulation of the TGFβ1-Smad signaling pathway, and enhances the synthesis and biopotency of TSH, the hormone secreted by thyrotropes. By contrast, IGSF1 strongly down-regulates the activin-Smad pathway, leading to reduced expression of FSHB, the hormone secreted by gonadotropes. In conclusion, two relevant molecular mechanisms linked to central hypothyroidism and macroorchidism in IGSF1 deficiency are identified, revealing IGSF1 as an important regulator of TGFβ/Activin pathways in the pituitary.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.