Rapid membrane effect of estrogens on stimulation of corticotropin-releasing hormone.
Psychoneuroendocrinology
; 117: 104680, 2020 07.
Article
in En
| MEDLINE
| ID: mdl-32387876
ABSTRACT
BACKGROUND:
Classic nuclear-initiated estrogen signaling stimulates corticotropin-releasing hormone (CRH) gene expression as a transcription factor. However, the possible mechanism by which membrane-initiated estrogen signaling (MIES) influences CRH expression remains unclear. There are indications that MIES may upregulate nitric oxide (NO) production through the phosphatidylinositol 3-hydroxy kinase (PI3K) and potentially through the mitogen-activated protein kinase (MAPK) pathway.OBJECTIVES:
We investigated the effect of MIES-mediated kinase pathways on CRH expression with or without NO synthesis.METHOD:
In SK-N-SH cell culture, estradiol-bovine serum albumin (E2-BSA) was used as the specific membrane estrogen receptor activator, with a specific NO donor, and/or inhibitors for NO synthase (NOS), PI3K, MAPK, protein kinase A (PKA), and protein kinase C (PKC).RESULTS:
E2-BSA significantly increased NO and CRH levels in the medium and NOS1-mRNA levels in the cells. In addition, NO donor up-regulated CRH expression, while NOS-inhibitor down-regulated it. When the inhibitor of MAPK and/or the inhibitor of PI3K was added to the medium, only the latter appeared to significantly block the stimulating effect of E2-BSA on NO synthesis, and this was accompanied by an increased CRH expression in the medium. We further studied the effect of the MIES-PKC-mediated pathway on CRH expression, with or without NOS-inhibitor, while the MIES-PKA(-PI3K) pathway served as a control. We found that MIES-PKC upregulated CRH expression independent of NO synthesis.CONCLUSION:
MIES can efficiently upregulate CRH expression via various intracellular kinase pathways and may thus be a crucial component in the stress response.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
/
Serum Albumin, Bovine
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Corticotropin-Releasing Hormone
/
Signal Transduction
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Receptors, Estrogen
/
Gene Expression Regulation
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Phosphatidylinositol 3-Kinases
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Estradiol
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Estrogens
/
Nitric Oxide
Limits:
Humans
Language:
En
Journal:
Psychoneuroendocrinology
Year:
2020
Document type:
Article