Document Detail


Phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine affects rabbit ovaries and oviduct.
MedLine Citation:
PMID:  20599929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of our study was to examine the influence of 3-isobutyl-1-methyl-xanthine (IBMX), an inhibitor of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) phosphodiesterases on rabbit reproductive system. The ovarian cycle and ovulation of control rabbits were induced by gonadotropin releasing hormone (GnRH) or equine chorionic gonadotropin (eCG) followed by the human chorionic gonadotropin (hCG) administration. Experimental animals received GnRH together with IBMX (at 50 or 500 microg/animal) or eCG and hCG together with IBMX (at 5 or 257 microg/animal). After mating and insemination, blood samples were collected and analyzed for concentrations of progesterone and estradiol by RIA; some animals from the control and IBMX-treated groups were killed. The presence of follicles at different stages of development was evaluated by a light microscopy. Isolated ovarian fragments were cultured for 2 days. The secretion of progesterone and estradiol was assessed by RIA. The expression of markers of proliferation (PCNA and cyclin B1) and apoptosis (bax) in ovarian fragments was evaluated by Western-blotting. Epithelial cells were isolated from oviducts and cultured for 2 days. The expression of markers of proliferation (PCNA, ERK1,2-related MAP kinase) and apoptosis (bax, bcl-2) in the oviductal cells was evaluated by immunocytochemistry. It was observed, that the ovaries of rabbits treated with IBMX contained more secondary follicles, than control rabbits. Administration of IBMX reduced blood level of progesterone, but did not affect blood estradiol. Fragments of ovaries isolated from rabbits treated with IBMX released more estradiol, but not progesterone, than ovarian cells isolated from the control animals. IBMX injections substantially decreased the expression of the upper (23 kD), but not the bottom (24 kD) fraction of bax. IBMX administration did not affect PCNA, but it caused a decrease in the upper fraction (54 kD) and an increase in the bottom fraction (55 kD) of cyclin B1. Oviductal cells isolated from the IBMX-treated animals, contained less marker of apoptosis - bax (but not bcl-2) and proliferation - ERK1,2-related MAP kinase (but not PCNA) than control animals. These observations demonstrate the involvement of cyclic nucleotide-dependent intracellular mechanisms in control of rabbit reproductive functions: ovarian folliculogenesis, apoptosis, proliferation and steroid hormone release, as well as proliferation and apoptosis of the oviductal cells.
Authors:
Alexander V Sirotkin; Peter Chrenek; Stella Chadio; Eftichia Xylouri; Helen Fotopouloy; Alexander V Makarevich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-17
Journal Detail:
Title:  European journal of pharmacology     Volume:  643     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  145-51     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Affiliation:
Institute of Animal Genetics and Reproduction, Animal Production Research Centre Nitra, 95141 Luzianky near Nitra, Slovak Republic. sirotkin@cvzv.sk
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-3-isobutylxanthine / pharmacology*
3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors
Animals
Apoptosis / drug effects
Cell Proliferation / drug effects
Estrous Cycle / drug effects
Female
Ovarian Follicle / drug effects,  enzymology,  pathology
Ovary / drug effects*,  enzymology,  pathology
Oviducts / drug effects*,  enzymology,  pathology
Ovulation / drug effects
Phosphodiesterase Inhibitors / pharmacology*
Rabbits
Chemical
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 28822-58-4/1-Methyl-3-isobutylxanthine; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases; EC 3.1.4.35/3',5'-Cyclic-GMP Phosphodiesterases

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


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