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Effects of leukemia inhibitory receptor gene mutations on human hypothalamo-pituitary-adrenal function

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dc.contributor.authorBEREKET, ABDULLAH
dc.contributor.authorsGuran, Tulay; Guran, Omer; Paketci, Cem; Kipoglu, Osman; Firat, Irfan; Turan, Serap; Atay, Zeynep; Haliloglu, Belma; Bereket, Abdullah
dc.date.accessioned2022-03-12T20:26:32Z
dc.date.available2022-03-12T20:26:32Z
dc.date.issued2015
dc.description.abstractStuve-Wiedemann syndrome (STWS) (MIM #601559) is a rare autosomal recessive disorder caused by mutations in the leukemia inhibitory factor receptor (LIFR) gene. STWS has a diverse range of clinical features involving hematopoietic, skeletal, neuronal and immune systems. STWS manifests a high mortality due to increased risk of sudden death. Heterodimerization of the LIFR mediates leukemia inhibitory factor (LIF) signalling through the intracellular Janus kinase (JAK)/STAT3 signalling cascade. The LIF/LIFR system is highly expressed in and regulates the hypothalamo-pituitary-adrenal (HPA) axis. HPA function was investigated in three STWS patients to characterise consequences of impaired LIF/LIFR signalling on adrenal function. Six genetically proven STWS patients from four unrelated Turkish families were included in the study. Sudden death occurred in three before 2 years of age. Basal adrenal function tests were performed by measurement of early morning serum cortisol and plasma ACTH concentrations on at least two different occasions. Low dose synacthen stimulation test and glucagon stimulation tests were performed to explore adrenal function in three patients who survived. All patients carried the same LIFR (p.Arg692X) mutation. Our oldest patient had attenuated morning serum cortisol and plasma ACTH levels at repeated measurements. Two of three patients had attenuated cortisol response (< 18 mu g/dl) to glucagon, one of whom also had borderline cortisol response to low dose (1 mu g) ACTH stimulation consistent with central adrenal insufficiency. STWS patients may develop central adrenal insufficiency due to impaired LIF/LIFR signalling. LIF/LIFR system plays a role in human HPA axis regulation.
dc.identifier.doi10.1007/s11102-014-0594-5
dc.identifier.eissn1573-7403
dc.identifier.issn1386-341X
dc.identifier.pubmed25145448
dc.identifier.urihttps://hdl.handle.net/11424/233477
dc.identifier.wosWOS:000356824300003
dc.language.isoeng
dc.publisherSPRINGER
dc.relation.ispartofPITUITARY
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectLIFR
dc.subjectStuve-Wiedemann
dc.subjectHypothalamo-pituitary-adrenal
dc.subjectJAK-STAT
dc.subjectFACTOR LIF
dc.subjectEXPRESSION
dc.subjectCHILDREN
dc.subjectSTEROIDOGENESIS
dc.subjectHORMONE
dc.subjectACTH
dc.subjectAXIS
dc.subjectINSUFFICIENCY
dc.subjectTRANSCRIPTION
dc.subjectACTIVATION
dc.titleEffects of leukemia inhibitory receptor gene mutations on human hypothalamo-pituitary-adrenal function
dc.typearticle
dspace.entity.typePublication
local.avesis.id236af404-061e-45ea-a005-c06cfae02a14
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages5
oaire.citation.endPage460
oaire.citation.issue4
oaire.citation.startPage456
oaire.citation.titlePITUITARY
oaire.citation.volume18
relation.isAuthorOfPublication669e9474-4e39-453f-a4bc-4ede9cb5abac
relation.isAuthorOfPublication.latestForDiscovery669e9474-4e39-453f-a4bc-4ede9cb5abac

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