Document Detail


17β-oestradiol acts as a negative modulator of insulin-induced lactotroph cell proliferation through oestrogen receptor α, via nitric oxide/guanylyl cyclase/cGMP.
MedLine Citation:
PMID:  20887556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 17β-oestradiol interacts with growth factors to modulate lactotroph cell population. However, contribution of isoforms of the oestrogen receptor in these activities is not fully understood. In the present study, we have established participation of α and β oestrogen receptors in effects of 17β-oestradiol on lactotroph proliferation induced by insulin and shown involvement of the NO/sGC/cGMP pathway.
MATERIALS AND METHODS: Cell cultures were prepared from anterior pituitaries of female rats to evaluate lactotroph cell proliferation using bromodeoxyuridine (BrdUrd) detection, protein expression by western blotting and cGMP by enzyme immunoassay.
RESULTS: In serum-free conditions, 17β-oestradiol and α and β oestrogen receptor agonists (PPT and DPN) failed to increase numbers of lactotroph cells undergoing mitosis. Co-incubation of 17β-oestradiol/insulin and PPT/insulin significantly decreased lactotroph mitogenic activity promoted by insulin alone. Both ICI 182780 and NOS inhibitors (L-NMMA and L-NAME) induced reversal of the anti-proliferative effect promoted by 17β-oestradiol/insulin and PPT/insulin. Moreover, 17β-oestradiol, PPT and insulin increased sGC α1 protein expression and inhibited β1, whereas co-incubation of 17β-oestradiol/insulin or PPT/insulin induced increases of the two isoforms α1 and β1. 17β-oestradiol and insulin reduced cGMP production, while 17β-oestradiol/insulin co-incubation increased this cyclic nucleotide.
CONCLUSIONS: Our results suggest that 17β-oestradiol is capable of arresting lactotroph proliferation induced by insulin through ER α with participation of the signalling NO/sGC/cGMP pathway.
Authors:
S Gutiérrez; J P Petiti; L d V Sosa; L Fozzatti; A L De Paul; A M Masini-Repiso; A I Torres
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell proliferation     Volume:  43     ISSN:  1365-2184     ISO Abbreviation:  Cell Prolif.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-27     Revised Date:  2012-02-29    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  505-14     Citation Subset:  IM    
Affiliation:
Center of Electron Microscopy, Faculty of Medical Sciences, National University of Córdoba, Córdoba, Argentina. silvina@cmefcm.uncor.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation*
Cells, Cultured
Cyclic GMP / metabolism
Estradiol / metabolism*
Estrogen Receptor alpha / metabolism*
Female
Guanylate Cyclase / metabolism*
Insulin / metabolism*
Lactotrophs / cytology*
Nitric Oxide / metabolism
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Insulin; 10102-43-9/Nitric Oxide; 50-28-2/Estradiol; 7665-99-8/Cyclic GMP; EC 4.6.1.2/Guanylate Cyclase

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