RGD Reference Report - Fibroblast growth factor-9, a local regulator of ovarian function. - Rat Genome Database

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Fibroblast growth factor-9, a local regulator of ovarian function.

Authors: Drummond, AE  Tellbach, M  Dyson, M  Findlay, JK 
Citation: Drummond AE, etal., Endocrinology. 2007 Aug;148(8):3711-21. Epub 2007 May 10.
RGD ID: 2289861
Pubmed: PMID:17494997   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2006-1668   (Journal Full-text)

Fibroblast growth factor 9 (FGF9) is widely expressed in embryos and fetuses and has been shown to be involved in male sex determination, testicular cord formation, and Sertoli cell differentiation. Given its male gender bias, the ovary has not been reported to express FGF9, nor has a role in ovarian function been explored. We report here that FGF9 mRNA and protein are present in the rat ovary and provide evidence that supports a role for FGF9 in ovarian progesterone production. FGF9 mRNA levels as determined by real-time PCR were high in 4-d-old rat ovaries, thereafter declining and stabilizing at levels approximately 30% of d 4 levels at d 12-25. Levels of FGF9 mRNA in the ovary were significantly higher than that present in adult testis, at all ages studied. The FGF9 receptors FGFR2 and FGFR3 mRNAs were present in postnatal and immature rat ovary and appeared to be constitutively expressed. FGF9 protein was localized to theca, stromal cells, and corpora lutea and FGFR2 and FGFR3 proteins to granulosa cells, theca cells, oocytes, and corpora lutea, by immunohistochemistry. Follicular differentiation induced by gonadotropin treatment reduced the expression of FGF9 mRNA by immature rat ovaries, whereas the estrogen-stimulated development of large preantral follicles had no significant effect. In vitro, FGF9 stimulated progesterone production by granulosa cells beyond that elicited by a maximally stimulating dose of FSH. When the granulosa cells were pretreated with FSH to induce LH receptors, FGF9 was found not to be as potent as LH in stimulating progesterone production, nor did it enhance LH-stimulated production. The combined treatments of FSH/FGF9 and FSH/LH, however, were most effective at stimulating progesterone production by these differentiated granulosa cells. Analyses of steroidogenic regulatory proteins indicate that steroidogenic acute regulatory protein and P450 side chain cleavage mRNA levels were enhanced by FGF9, providing a mechanism of action for the increased progesterone synthesis. In summary, the data are consistent with a paracrine role for FGF9 in the ovary.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to fibroblast growth factor stimulus  IEP 2289861; 2289861; 2289861FGF-9RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
basement membrane  IDA 2289861ovarian granulosa cells and follicles and seminiferous tubulesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp11a1  (cytochrome P450, family 11, subfamily a, polypeptide 1)
Fgf9  (fibroblast growth factor 9)
Hsd3b1  (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1)
Star  (steroidogenic acute regulatory protein)

Objects referenced in this article
Gene Fgfr2 fibroblast growth factor receptor 2 Rattus norvegicus
Gene Fgfr3 fibroblast growth factor receptor 3 Rattus norvegicus

Additional Information