RGD Reference Report - ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism. - Rat Genome Database

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ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism.

Authors: Castinetti, F  Brinkmeier, ML  Mortensen, AH  Vella, KR  Gergics, P  Brue, T  Hollenberg, AN  Gan, L  Camper, SA 
Citation: Castinetti F, etal., Mol Endocrinol. 2015 Oct;29(10):1510-21. doi: 10.1210/me.2015-1192. Epub 2015 Aug 21.
RGD ID: 11353031
Pubmed: PMID:26296153   (View Abstract at PubMed)
PMCID: PMC4588728   (View Article at PubMed Central)
DOI: DOI:10.1210/me.2015-1192   (Journal Full-text)

ISLET1 is a homeodomain transcription factor necessary for development of the pituitary, retina, motor neurons, heart, and pancreas. Isl1-deficient mice (Isl1(-/-)) die early during embryogenesis at embryonic day 10.5 due to heart defects, and at that time, they have an undersized pituitary primordium. ISL1 is expressed in differentiating pituitary cells in early embryogenesis. Here, we report the cell-specific expression of ISL1 and assessment of its role in gonadotropes and thyrotropes. Isl1 expression is elevated in pituitaries of Cga(-/-) mice, a model of hypothyroidism with thyrotrope hypertrophy and hyperplasia. Thyrotrope-specific disruption of Isl1 with Tshb-cre is permissive for normal serum TSH, but T4 levels are decreased, suggesting decreased thyrotrope function. Inducing hypothyroidism in normal mice causes a reduction in T4 levels and dramatically elevated TSH response, but mice with thyrotrope-specific disruption of Isl1 have a blunted TSH response. In contrast, deletion of Isl1 in gonadotropes with an Lhb-cre transgene has no obvious effect on gonadotrope function or fertility. These results show that ISL1 is necessary for maximal thyrotrope response to hypothyroidism, in addition to its role in development of Rathke's pouch.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ISL1Humanhypothyroidism susceptibilityISOIsl1 (Mus musculus) RGD 
Isl1Rathypothyroidism susceptibilityISOIsl1 (Mus musculus) RGD 
Isl1Mousehypothyroidism susceptibilityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Isl1  (ISL LIM homeobox 1)

Genes (Mus musculus)
Isl1  (ISL1 transcription factor, LIM/homeodomain)

Genes (Homo sapiens)
ISL1  (ISL LIM homeobox 1)

Additional Information