RGD Reference Report - The GH-IGF-IGFBP axis is changed in Turner syndrome: partial normalization by HRT. - Rat Genome Database

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The GH-IGF-IGFBP axis is changed in Turner syndrome: partial normalization by HRT.

Authors: Gravholt, Claus HĂžjbjerg  Chen, Jian-Wen  Oxvig, Claus  Overgaard, Michael T  Christiansen, Jens Sandahl  Frystyk, Jan  Flyvbjerg, Allan 
Citation: Gravholt CH, etal., Growth Horm IGF Res. 2006 Oct-Dec;16(5-6):332-9. Epub 2006 Oct 25.
RGD ID: 12743588
Pubmed: PMID:17067837   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ghir.2006.09.001   (Journal Full-text)

BACKGROUND: We recently described increased insulin-like growth factor binding protein 3 (IGFBP-3) proteolysis in the circulation in adult Turner syndrome (TS), with normalization during sex hormone replacement therapy (HRT), suggesting the presence of a sex hormone regulated IGFBP-3 proteolytic activity.
OBJECTIVE: To study the GH-IGF-IGFBP axis in TS without and during HRT, and to further characterize the nature of the IGFBP-3 proteolytic activity.
MATERIAL: 23 women with TS before and during HRT, and 24 healthy age-matched women.
METHODS: The study included measurements of the acid-labile subunit (ALS), IGFBP-1, -2 and -3 (immunoreactive and Western ligand blot (WLB)), IGFBP-4 (WLB) and IGF-I bioactivity. To determine the molecular distribution of IGFBP-3, serum from patient and controls was subjected to neutral size-exclusion chromatography followed by determination of the IGFBP profile by WLB and immunoassay. Finally, the inhibitor characteristic of in vitro IGFBP-3 proteolytic activity in serum was determined.
RESULTS: Immunoreactive IGF-I was normal, while IGF-I bioactivity was decreased in TS. Immunoreactive IGFBP-1, -2 and -3 were normal, while WLB-IGFBPs were all reduced, but increased in response to HRT. The IGFBP-3 ternary complex was significantly reduced in TS, and increased in response to HRT, while the non-ternary complexed IGFBP-3 remained unaffected by treatment. In vitro IGFBP-3 proteolytic activity in serum was abolished by aprotinin, while EDTA and zinc chloride had no inhibitory effects, suggesting the presence of a serine protease. 17beta-estradiol had no direct inhibitory effect on the IGFBP-3 proteolytic activity in vitro. Size-exclusion chromatography showed that the protease had a molecular mass of more than 500 kDa.
CONCLUSION: The GH-IGF-IGFBP axis is profoundly disturbed in TS, with a partly normalizing effect of HRT. A sex hormone-dependent IGFBP-3 proteolytic activity (serine protease) leads to destabilization of the 150 kDa IGFBP-3 ternary complex in TS. During HRT both IGFBP-3 proteolytic activity and ternary complex formation is normalized.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IGF1HumanTurner syndrome  IEP protein:decreased activity:serum:RGD 
IGFBP3HumanTurner syndrome  IDA  RGD 
Igf1RatTurner syndrome  ISOIGF1 (Homo sapiens)protein:decreased activity:serum:RGD 
Igf1MouseTurner syndrome  ISOIGF1 (Homo sapiens)protein:decreased activity:serum:RGD 
Igfbp3RatTurner syndrome  ISOIGFBP3 (Homo sapiens) RGD 
Igfbp3MouseTurner syndrome  ISOIGFBP3 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)
Igfbp3  (insulin-like growth factor binding protein 3)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)
Igfbp3  (insulin-like growth factor binding protein 3)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)
IGFBP3  (insulin like growth factor binding protein 3)

Additional Information