Document Detail


IGF-I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells.
MedLine Citation:
PMID:  23340251     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR.
Authors:
Ping Zhou; Sarah C Baumgarten; Yanguang Wu; Jill Bennett; Nicola Winston; Jennifer Hirshfeld-Cytron; Carlos Stocco
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-22
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  27     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-10-17     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  511-23     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects
Cyclic AMP Response Element-Binding Protein / metabolism
Enzyme Activation / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Follicle Stimulating Hormone / pharmacology*
Gene Expression Regulation / drug effects*
Granulosa Cells / cytology,  drug effects,  enzymology*
HEK293 Cells
Humans
Insulin-Like Growth Factor I / metabolism*
Mice
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / genetics*,  metabolism
Rats
Rats, Sprague-Dawley
Receptor, IGF Type 1 / metabolism
Receptors, FSH / metabolism
Signal Transduction* / drug effects
Species Specificity
Steroids / metabolism*
Grant Support
ID/Acronym/Agency:
R01HD057110/HD/NICHD NIH HHS; R21HD066233/HD/NICHD NIH HHS; T32 HL007692/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Receptors, FSH; 0/Steroids; 67763-96-6/Insulin-Like Growth Factor I; 9002-68-0/Follicle Stimulating Hormone; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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