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Proton Sensitivity of Corticotropin-Releasing Hormone Receptor 1 Signaling to Proopiomelanocortin in Male Mice.

Endocrinology | 2019

Because an acidic cellular microenvironment is engendered by inflammation and may determine cell differentiation, we elucidated the impact of acidic conditions on induction of proopiomelanocortin (POMC) expression. Here, we demonstrate mechanisms for proton sensitivity of CRH receptor 1 (CRHR1) signaling to POMC and ACTH production. Low pH (6.8) resulted in doubling of POMC expression and ACTH production in pituitary cell line AtT-20 and in primary mouse pituitary cells. Using CRISPR knockout, we show that CRHR1 is necessary for acid-induced POMC expression, and this induction is mediated by CRHR1 histidine residues and calmodulin-dependent protein kinase II in both pituitary corticotroph cells and in nonpituitary cell lines expressing ectopic ACTH. In contrast, CRH ligand binding affinity to CRHR1 was decreased with acidic pH, implying that proton-induced POMC expression prevails in acidic conditions independently of CRH ligand binding. The results indicate that proton-induced CRHR1 signaling regulates ACTH production in response to an acidic microenvironment.

Pubmed ID: 30535142 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK113998
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007770

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This is a list of tools and resources that we have found mentioned in this publication.


CRF-RI/II (C-20) (antibody)

RRID:AB_673600

This polyclonal targets CRHR1, CRHR2

View all literature mentions

NUR77 antibody (antibody)

RRID:AB_10644125

This polyclonal targets NUR77

View all literature mentions

Phospho-CREB (Ser133) (87G3) Rabbit mAb (antibody)

RRID:AB_2561044

This monoclonal targets Phospho-CREB (Ser133)

View all literature mentions

CREB antibody [5G3] (antibody)

RRID:AB_10858949

This monoclonal targets CREB antibody [5G3]

View all literature mentions

Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

View all literature mentions

PITX1 antibody (antibody)

RRID:AB_10859664

This polyclonal targets PITX1

View all literature mentions

p44/42 MAPK (Erk1/2) Antibody (antibody)

RRID:AB_330744

This polyclonal targets p44/42 MAPK (Erk1/2)

View all literature mentions

Anti-POMC antibody (antibody)

RRID:AB_777375

This polyclonal targets POMC

View all literature mentions

Anti-CRHR1 antibody produced in rabbit (antibody)

RRID:AB_10744295

This polyclonal targets CRHR1 antibody produced in rabbit

View all literature mentions

B16-F0 (cell line)

RRID:CVCL_0604

Cell line B16-F0 is a Cancer cell line with a species of origin Mus musculus (Mouse)

View all literature mentions

COLO 320DM (cell line)

RRID:CVCL_0219

Cell line COLO 320DM is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MCF-7 (cell line)

RRID:CVCL_0031

Cell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

AtT-20/D16v-F2 (cell line)

RRID:CVCL_4109

Cell line AtT-20/D16v-F2 is a Cancer cell line with a species of origin Mus musculus (Mouse)

View all literature mentions

HeLa (cell line)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

DMS 79 (cell line)

RRID:CVCL_1178

Cell line DMS 79 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

View all literature mentions

Phospho-CREB (Ser133) (87G3) Rabbit mAb (antibody)

RRID:AB_2561044

This monoclonal targets Phospho-CREB (Ser133)

View all literature mentions

Anti-POMC antibody (antibody)

RRID:AB_777375

This polyclonal targets POMC

View all literature mentions

B16-F0 (cell line)

RRID:CVCL_0604

Cell line B16-F0 is a Cancer cell line with a species of origin Mus musculus (Mouse)

View all literature mentions

HeLa (cell line)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

MCF-7 (cell line)

RRID:CVCL_0031

Cell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

DMS 79 (cell line)

RRID:CVCL_1178

Cell line DMS 79 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

COLO 320DM (cell line)

RRID:CVCL_0219

Cell line COLO 320DM is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

AtT-20/D16v-F2 (cell line)

RRID:CVCL_4109

Cell line AtT-20/D16v-F2 is a Cancer cell line with a species of origin Mus musculus (Mouse)

View all literature mentions

CREB antibody [5G3] (antibody)

RRID:AB_10858949

This monoclonal targets CREB antibody [5G3]

View all literature mentions

p44/42 MAPK (Erk1/2) Antibody (antibody)

RRID:AB_330744

This polyclonal targets p44/42 MAPK (Erk1/2)

View all literature mentions

PITX1 antibody (antibody)

RRID:AB_10859664

This polyclonal targets PITX1

View all literature mentions

Anti-CRHR1 antibody produced in rabbit (antibody)

RRID:AB_10744295

This polyclonal targets CRHR1 antibody produced in rabbit

View all literature mentions

NUR77 antibody (antibody)

RRID:AB_10644125

This polyclonal targets NUR77

View all literature mentions