Evidence map›Paper›PMID 21964592›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2011

PITX2 AND PITX1 regulate thyrotroph function and response to hypothyroidism.

F Castinetti, M L Brinkmeier, D F Gordon, K R Vella, J M Kerr, A H Mortensen, A Hollenberg, T Brue, E C Ridgway, S A Camper

Open access · bronzeAbstract read
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Pitx genes in development and disease.Cellular and molecular life sciences : CMLS · 2021
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Recent advances in central congenital hypothyroidism.The Journal of endocrinology · 2015
    Review
  12. ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism.Molecular endocrinology (Baltimore, Md.) · 2015
    Article
  13. Genetic regulation of murine pituitary development.Journal of molecular endocrinology · 2015
    Review
  14. Article
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

F CastinettiDepartment of Human Genetics, University of Michigan, Ann Arbor, USA.
M L Brinkmeier
D F Gordon
K R Vella
J M Kerr
A H Mortensen
A Hollenberg
T Brue
E C Ridgway
S A Camper
University of Michigan–Ann Arbor · USHarvard University · USUniversity of Colorado Denver · USAix-Marseille Université · FRUniversity of Colorado Anschutz Medical Campus · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Michael Schuetze · 1988 to 2026
$178.2M
PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILEY, JOHN W · 1986 to 2021
$22.5M
CELL-SPECIFIC EXPRESSION IN THE PITUITARY GLANDR01HD034283 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CAMPER, SALLY A. · 1996 to 2021
$7.7M
A Panhypopitutitary Mouse MutationR37HD030428 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CAMPER, SALLY A. · 2002 to 2011
$3.4M
UNIVERSITY OF MICHIGAN MULTIPURPOSE ARTHRITIS CENTERP60AR020557 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GRUPPEN, LARRY D · 1986 to 2001
$2.9M
NCI NIH HHS CA46592NCI NIH HHS P30 CA046592NIAMS NIH HHS AR20557NICHD NIH HHS R01 HD034283NICHD NIH HHS R01HD34283NICHD NIH HHS R37 HD030428NICHD NIH HHS R37HD30428NIDDK NIH HHS DK20572NIDDK NIH HHS DK34933NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P30DK08194NIDDK NIH HHS P60 DK020572
6 · The paper itself

Abstract

Pitx2 is a homeodomain transcription factor required in a dose-dependent manner for the development of multiple organs. Pitx2-null homozygotes (Pitx2(-/-)) have severe pituitary hypoplasia, whereas mice with reduced-function alleles (Pitx2(neo/neo)) exhibit modest hypoplasia and reduction in the developing gonadotroph and Pou1f1 lineages. PITX2 is expressed broadly in Rathke's pouch and the fetal pituitary gland. It predominates in adult thyrotrophs and gonadotrophs, although it is not necessary for gonadotroph function. To test the role of PITX2 in thyrotroph function, we developed thyrotroph-specific cre transgenic mice, Tg(Tshb-cre) with a recombineered Tshb bacterial artificial chromosome that ablates floxed genes in differentiated pituitary thyrotrophs. We used the best Tg(Tshb-Cre) strain to generate thyrotroph-specific Pitx2-deficient offspring, Pitx2(flox/-;)Tg(Tshb-cre). Double immunohistochemistry confirmed Pitx2 deletion. Pitx2(flox/-);Tg(Tshb-cre) mice have a modest weight decrease. The thyroid glands are smaller, although circulating T(4) and TSH levels are in the normal range. The pituitary levels of Pitx1 transcripts are significantly increased, suggesting a compensatory mechanism. Hypothyroidism induced by low-iodine diet and oral propylthiouracil revealed a blunted TSH response in Pitx2(flox/-);Tg(Tshb-cre) mice. Pitx1 transcripts increased significantly in control mice with induced hypothyroidism, but they remained unchanged in Pitx2(flox/-);Tg(Tshb-cre) mice, possibly because Pitx1 levels were already maximally elevated in untreated mutants. These results suggest that PITX2 and PITX1 have overlapping roles in thyrotroph function and response to hypothyroidism. The novel cre transgene that we report will be useful for studying the function of other genes in thyrotrophs.

Indexed as

AnimalsChromosomes, Artificial, BacterialFemaleHomeobox Protein PITX2Homeodomain ProteinsHypothyroidismImmunohistochemistryMaleMiceMice, TransgenicPaired Box Transcription FactorsPropylthiouracilThyrotrophsThyrotropin, beta SubunitTranscription Factorshomeobox protein PITX1Homeobox Protein PITX2Homeodomain ProteinsPaired Box Transcription FactorsPropylthiouracilThyrotropin, beta SubunitTranscription Factors

Identifiers

PMID21964592
PMCPMC3386545
OpenAlexW2050313474

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.