Impairment of the Hypothalamus–Pituitary–Thyroid Axis Caused by Naturally Occurring GATA2 Mutations In Vitro

Sakai, Yuki; Ohba, Kenji; Sasaki, Shigekazu; Matsushita, Akio; Nakamura, Hiroko; Kuroda, Go; Tsuriya, Daisuke; Yamashita, Miho; Suda, Takafumi

doi:10.3390/ijms221810015

Cited by 3 publications

(2 citation statements)

References 43 publications

(93 reference statements)

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“…Circulating concentrations of thyroid hormones are tightly regulated by the hypothalamus-pituitary-thyroid axis in healthy individuals [14][15][16]. Briefly, thyrotropinreleasing hormone acts on the anterior pituitary gland to synthesize and secrete TSH, which then stimulates the thyroid gland to synthesize and release thyroid hormones, including the prohormone thyroxine (T4) and the active form triiodothyronine (T3).…”

Section: Mechanisms Of Thyroid Hormone Actionmentioning

confidence: 99%

Role of thyroid hormone in an experimental model of atherosclerosis: the potential mediating role of immune response and autophagy

Ohba

Iwaki

2022

Endocr J

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Accumulating evidence has revealed that several conditions related to abnormal thyroid hormone status, such as dyslipidemia, hypertension, or hypercoagulable state, can exacerbate atherosclerotic vascular disease. Thyroid hormone effects on vascular smooth muscle cells and endothelial cells have also been studied extensively. However, only limited information is available on thyroid hormone-mediated immune response in current review articles on the pathophysiology of atherosclerosis. This report thus presents an overview of the recent advances in the understanding of the dynamic interactions taking place between thyroid hormone status and immune response in the pathogenesis of atherosclerosis. In particular, we focus on macrophages and T-lymphocytes, which have been recognized as important determinants for the initiation and development of atherosclerosis. Numerous studies have revealed the role of autophagy in immune cells produced in atherosclerosis. In addition, thyroid hormones induce autophagy in several cells and tissues, such as liver, skeletal muscles, lungs, and brown adipose tissue. Our research group, among others, have reported different targets of thyroid hormonemediated autophagy, including lipid droplets (lipophagy), mitochondria (mitophagy), and aggregated proteins (aggrephagy). Based on these findings, thyroid hormone-mediated autophagy could serve as a novel therapeutic approach for atherosclerosis. We also consider the limitations of the current murine models for studies on atherosclerosis, especially in relation to lowdensity lipoprotein-cholesterol driven atherosclerotic plaque.

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Section: Mechanisms Of Thyroid Hormone Actionmentioning

confidence: 99%

Role of thyroid hormone in an experimental model of atherosclerosis: the potential mediating role of immune response and autophagy

Ohba

Iwaki

2022

Endocr J

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“…This receptor is notorious in breast cancer pathological mechanisms and has a major clinical value in its diagnosis [9]. Mutations of the transcription factor GATA2 are required for the development of the gonadotroph and thyrotroph pituitary neuroendocrine tumors [10,11]. The estrogen receptors (ERs) and the GATA2 transcription factor have no tumoral type assigned but they may be involved indirectly in the clinical classification [8,10].…”

Section: Introductionmentioning

confidence: 99%

Surgical approaches in pituitary neuroendocrine tumors

Croitoru,

Andronachi,

Visnevschi

et al. 2024

MJHS

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Introduction. Pituitary neuroendocrine tumors account for 3.9-7.4/100.000 of central nervous system tumors in the Western world. They are particularly noteworthy, comprising 10-15% of all cases, with a higher prevalence in the 75-79 age group. In the Republic of Moldova, these tumors account for 34% of cases in postmortem examinations while remain an actual theme of discussion in the ENDO WHO congress and are regarded as a factor, which may influence the quality of life (QOL). Material and methods. We have critically revised 66 literary sources, which were selected using the PubMed library after introducing the keywords “pituitary adenoma surgical approach”. Results. The main surgical approaches were the transsphenoidal (transnasal, sublabial and endonasal) and transcranial (subfrontal unilateral/bilateral, fronto-lateral, fronto-temporal and median basilar) while the additional surgical approaches were designed for complicated and unusual pituitary neuroendocrine tumors and included combined versions, multiple surgeries or extended approaches. Numerous factors were influential for the selection of a surgical approach concerning the pituitary neuroendocrine tumors. They are not sensible for a type of pituitary neuroendocrine tumor according to the WHO classification while the size of a tumor may dictate its surgical approach. Conclusion. Each surgical intervention requires a personalized approach and the critical thinking of the surgical team but most of them can be systematically considered before confronting the tumor in an intraoperatory environment because most of the preoperatory investigations are proven unreliable. There is no established superior surgical approach for each surgical intervention.

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A novel GATA2 distal enhancer mutation results in MonoMAC syndrome in 2 second cousins

West,

Bauer,

Tuschong

et al. 2023

Blood Advances

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Inherited or de novo germline mutations in the transcription factor GATA2 have been shown to be responsible for MonoMAC syndrome, a GATA2 deficiency disease characterized by a constellation of findings, including: disseminated non-tuberculous mycobacterial infections, severe deficiencies of monocytes, natural killer cells, and B-lymphocytes, and myelodysplastic syndrome. Mutations in the GATA2 gene are found in ~90% of patients with a GATA2 deficiency phenotype and are largely missense mutations in the conserved second zinc-finger domain or truncation mutations elsewhere in the coding sequence. Mutations in an intron 5 regulatory enhancer element are also well described in GATA2 deficiency. Here we present a large multigeneration kindred with the clinical features of GATA2 deficiency, but lacking an apparent GATA2 mutation. Whole Genome Sequencing revealed a unique adenine-to-thymine variant in the GATA2 -110 enhancer 116,855bp upstream of the GATA2 gene ATG start site. The mutation creates a new E-box consensus in position with an existing GATA-box to generate a new hematopoietic regulatory composite element. The mutation segregates with the disease pattern in several generations of the family pedigree. Cell-type specific allelic imbalance of GATA2 expression is observed in a patient's bone marrow with higher expression from the mutant-linked allele. Allele-specific overexpression of GATA2 is observed in CRISPR/Cas9-modified HL-60 cultured cells and in luciferase assays with the enhancer mutation. This study demonstrates overexpression of GATA2 resulting from a single nucleotide change in an upstream regulatory enhancer element in patients with MonoMAC syndrome. Patients in this study were enrolled in National Institute of Allergy and Infectious Diseases clinical trial Clinicaltrials.gov identifier NCT01905826 and National Cancer Institute clinical trial Clinicaltrials.gov identifier NCT01861106.

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Impairment of the Hypothalamus–Pituitary–Thyroid Axis Caused by Naturally Occurring GATA2 Mutations In Vitro

Cited by 3 publications

References 43 publications

Role of thyroid hormone in an experimental model of atherosclerosis: the potential mediating role of immune response and autophagy

Role of thyroid hormone in an experimental model of atherosclerosis: the potential mediating role of immune response and autophagy

Surgical approaches in pituitary neuroendocrine tumors

A novel GATA2 distal enhancer mutation results in MonoMAC syndrome in 2 second cousins

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