Document Detail


Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells.
MedLine Citation:
PMID:  16648300     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In addition to gonadotropins, steroidogenesis and proliferation of granulosa cells during follicular development are controlled by a number of intraovarian factors including growth differentiation factor-9 (GDF-9), bone morphogenetic protein-4 (BMP-4), and IGF-I. The objective of this study was to determine the effect of GDF-9 and BMP-4 and their interaction with IGF-I and FSH on ovarian granulosa cell function in cattle. Granulosa cells from small (1-5 mm) and large (8-22 mm) follicles were collected from bovine ovaries and cultured for 48 h in medium containing 10% fetal calf serum and then treated with various hormones in serum-free medium for an additional 48 h. We evaluated the effects of GDF-9 (150-600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced steroidogenesis and cell proliferation. In FSH plus IGF-I-treated granulosa cells obtained from small follicles, 300 ng/ml GDF-9 reduced (P < 0.05) progesterone production by 15% and 600 ng/ml GDF-9 completely blocked (P < 0.01) the IGF-I-induced increase in progesterone production. In comparison, 300 and 600 ng/ml GDF-9 decreased (P < 0.05) estradiol production by 27% and 71% respectively, whereas 150 ng/ml GDF-9 was without effect (P > 0.10). Treatment with 600 ng/ml GDF-9 increased (P < 0.05) numbers (by 28%) of granulosa cells from small follicles. In the same cells treated with FSH but not IGF-I, co-treatment with 600 ng/ml GDF-9 decreased (P < 0.05) progesterone production (by 28%), increased (P < 0.05) cell numbers (by 60%), and had no effect (P > 0.10) on estradiol production. In FSH plus IGF-I-treated granulosa cells obtained from large follicles, GDF-9 caused a dose-dependent decrease (P<0.05) in IGF-I-induced progesterone (by 13-48%) and estradiol (by 20-51%) production. In contrast, GDF-9 increased basal and IGF-I-induced granulosa cell numbers by over 2-fold. Furthermore, treatment with BMP-4 also inhibited (P < 0.05) steroidogenesis by 27-42% but had no effect on cell numbers. To elucidate downstream signaling pathways, granulosa cells from small follicles were transfected with similar to mothers against decapentaplegics (Smad) binding element (CAGA)- or BMP response element (BRE)-promoter reporter constructs. Treatment with GDF-9 (but not BMP-4) activated the Smad3-induced CAGA promoter activity, whereas BMP-4 (but not GDF-9) activated the Smad1/5/8-induced BRE promoter activity. We have concluded that bovine granulosa cells are targets of both GDF-9 and BMP-4, and that oocyte-derived GDF-9 may simultaneously promote granulosa cell proliferation and prevent premature differentiation of the granulosa cells during growth of follicles, whereas theca-derived BMP-4 may also prevent premature follicular differentiation.
Authors:
L J Spicer; P Y Aad; D Allen; S Mazerbourg; A J Hsueh
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of endocrinology     Volume:  189     ISSN:  0022-0795     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-01     Completed Date:  2006-06-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  329-39     Citation Subset:  IM    
Affiliation:
Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA. igf1Leo@okstate.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins / pharmacology*
Cattle
Cell Count
Cell Division / physiology
Cell Line
Culture Media, Conditioned
Dose-Response Relationship, Drug
Estradiol / biosynthesis
Female
Follicle Stimulating Hormone / physiology*
Granulosa Cells / drug effects,  physiology*
Growth Differentiation Factor 9
Insulin-Like Growth Factor I / physiology*
Intercellular Signaling Peptides and Proteins / pharmacology*
Progesterone / biosynthesis
Promoter Regions, Genetic / genetics
Recombinant Proteins / pharmacology
Signal Transduction / physiology
Smad Proteins / metabolism
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 0/Culture Media, Conditioned; 0/Growth Differentiation Factor 9; 0/Intercellular Signaling Peptides and Proteins; 0/Recombinant Proteins; 0/Smad Proteins; 50-28-2/Estradiol; 57-83-0/Progesterone; 67763-96-6/Insulin-Like Growth Factor I; 9002-68-0/Follicle Stimulating Hormone

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