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HPMR

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Tumor Necrosis Factor Receptor Superfamily, Member 12a OKDB#: 2205
 Symbols: TNFRSF12A Species: human
 Synonyms: FN14, CD266, TWEAKR,TYPE I TRANSMEMBRANE PROTEIN FN14, FN14|TWEAK RECEPTOR, TWEAKR  Locus: 16p13.3 in Homo sapiens
HPMR


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General Comment
General function Receptor
Comment
Cellular localization Plasma membrane
Comment
Ovarian function Ovulation, Steroid metabolism, Luteinization
Comment
Expression regulated by LH
Comment
Ovarian localization Granulosa
Comment Intraovarian TWEAK/Fn14 ligand-receptor system limits ovarian preovulatory follicles from excessive luteinization. De A et al. In addition to gonadotropins, many ovarian paracrine factors are crucial for optimal follicle rupture, oocyte maturation, and luteinization. Based on DNA microarray analyses, we found that transcripts for the fibroblast growth factor inducible-14 (Fn14) receptor are increased following LH/hCG treatment of gonadotropin-primed immature mice or rats. Fn14 is the cognate receptor for TNF-related weak inducer of apoptosis (TWEAK), a tumor necrosis factor superfamily member. TWEAK transcripts also were detected in the ovary; however, their levels were not regulated by gonadotropins. In situ hybridization analyses indicated that the Fn14 receptor is expressed in the granulosa and cumulus cells of preovulatory follicles, and to a lesser extent in theca cells. In contrast, in situ hybridization analyses revealed that TWEAK is primarily expressed in theca cells. In cultured granulosa cells pretreated with hCG to induce Fn14 receptor expression, treatment with TWEAK suppressed progesterone synthesis without accompanying changes in cAMP production. Furthermore, intrabursal injection of TWEAK suppressed ovarian progesterone content in gonadotropin-primed rats. In contrast, preovulatory follicles cultured in the presence of the Fn14 decoy, a recombinant protein containing the ligand-binding domain of Fn14, led to increases in progesterone production, presumably by antagonizing the actions of endogenous TWEAK. Likewise, ip injection of the Fn14 decoy enhanced serum progesterone levels with accompanying increases in transcript levels for several key steroidogenic enzymes. The present findings demonstrate a suppressive role of the TWEAK/Fn14 signaling system in the ovary. Following gonadotropin induction of ovulation, Fn14 is induced and could protect preovulatory follicles from excessive luteinization.
Follicle stages Preovulatory
Comment
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: Oct. 14, 2003, 12:22 p.m. by: xin   email:
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last update: July 18, 2006, 3:23 p.m. by: hsueh    email:



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