ArticleThe Journal of clinical endocrinology and metabolism2010
TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood.
Article in The Journal of clinical endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00494169 (Molecular Basis of Inherited Reproductive Disorders), which is not on this map. Cited by 133 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Molecular Basis of Inherited Reproductive Disorders
Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 288 citations in OpenAlex.
- Reversal of Congenital Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty.The Journal of clinical endocrinology and metabolism · 2016Trial
- Neurokinin B administration induces hot flushes in women.Scientific reports · 2015Trial
- Effects of neurokinin B administration on reproductive hormone secretion in healthy men and women.The Journal of clinical endocrinology and metabolism · 2014Trial
- Responsiveness to a physiological regimen of GnRH therapy and relation to genotype in women with isolated hypogonadotropic hypogonadism.The Journal of clinical endocrinology and metabolism · 2013Trial
- Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies: physiological, pathophysiological and therapeutic implications.Neuroendocrinology · 2013Trial
- Genetic landscape of a neonatal hypogonadotropic hypogonadism series: Novel variants and phenotypic spectrum.Journal of neuroendocrinology · 2026Article
- Identification of a Novel Splice-Site variant in TACR3 (c.888 + 1G > A) Associated with Asthenozoospermia and Hypogonadotropic Hypogonadism in an Iranian Family.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Identification of a Novel Splice-Site variant in TACR3 (c.888 + 1G > A) Associated with Asthenozoospermia and Hypogonadotropic Hypogonadism in an Iranian Family.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026Review
- Reversible congenital hypogonadotropic hypogonadism: keys for clinical management.Archives of endocrinology and metabolism · 2026Review
- Article
- Nonobstructive azoospermia: an etiologic review.Asian journal of andrology · 2025Review
- Kisspeptin and neurokinin B: roles in reproductive health.Physiological reviews · 2025Review
- Lack of a genetic risk continuum between pubertal timing in the general population and idiopathic hypogonadotropic hypogonadism.Journal of neuroendocrinology · 2024Article
- Arcuate Nucleus of the Hypothalamus: Anatomy, Physiology, and Diseases.Experimental neurobiology · 2023Review
- Insights into the genetics of menopausal vasomotor symptoms: genome-wide analyses of routinely-collected primary care health records.BMC medical genomics · 2023Article
- MKRN3 inhibits puberty onset via interaction with IGF2BP1 and regulation of hypothalamic plasticity.JCI insight · 2023Article
- Panel testing for the molecular genetic diagnosis of congenital hypogonadotropic hypogonadism - a clinical perspective.European journal of human genetics : EJHG · 2023Review
- Effect of CPP-related genes on GnRH secretion and Notch signaling pathway during puberty.Biomedical journal · 2023Review
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 11 institutions in 4 countries.
Funding
Abstract
contextMutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established.
objectiveA broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. DESIGN AND
settingThe study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. PATIENTS OR OTHER
participants345 probands, 18 family members, and 292 controls were studied.
interventionReproductive phenotypes throughout reproductive life and before and after therapy were examined.
main outcome measureRare sequence variants in TAC3/TACR3 were detected.
resultsIn TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism.
conclusionsMutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.
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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.