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1: Endocrinology. 2007 Aug;148(8):3711-21. Epub 2007 May 10.

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

Drummond AE, Tellbach M, Dyson M, Findlay JK.

Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria
3168, Australia. [e-mail]

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.

PMID: 17494997 [PubMed - indexed for MEDLINE]

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