PARENT SESSION

(T731) REGULATION OF FSH GENE EXPRESSION IN LT2 CELLS.

Yamada, Yoko¹, Yamamoto, Hideyuki², Kanasaki, Haruhiko¹, Miyazaki, Kohji¹, ¹ Shimane University School of Medicine, Izumo, Japan² Kumamoto University, Kumamoto, Japan

ABSTRACT- Follicle-stimulating hormone (FSH) consists of - and -subunits, and synthesis of -subunit has been reported to be the rate-limiting step in FSH production. In this study, we examined the effect of gonadotropin-releasing hormone (GnRH) on the rat FSH promoter activity in the gonadotrope cell line, LT2 cells. We constructed the luciferase reporter gene after rat FSH promoter. We found that GnRH and activin A activated FSH promoter and that the response to a combination of GnRH and activin A was higher than that to activin A or GnRH alone. The activation of FSH promoter by GnRH was inhibited strongly by U0126, a MAP kinase kinase (MEK) inhibitor, and slightly by calphostin C, a protein kinase C inhibitor. GnRH, but not activin A, activated MAP kinase in LT2 cells. Overexpression of constitutively active MEK1 or MEK kinase (MEKK) strongly activated MAP kinase. However, overexpression of MEKK only slightly activated FSH promoter and no activation was observed by overexpression of MEK1. These results suggest that activation of the MAP kinase pathway is necessary but not sufficient for GnRH-induced activation of FSH promoter.

KEY WORDS: FSH, GnRH, MAP kinase, activin