Zg. Chen et al., GLUCOCORTICOIDS MODULATE HUMAN GONADOTROPIN-RELEASING-HORMONE UPSTREAM PROMOTER ACTIVITY IN TRANSFECTED HUMAN PLACENTAL CELLS (JEG-3), Molecular human reproduction, 4(1), 1998, pp. 93-99
A human gonadotrophin releasing hormone (GnRH) upstream promoter/lucif
erase reporter gene construct (H2 construct) was generated by insertin
g a 1.7 kb Xbal/Afll fragment containing the human GnRH upstream promo
ter region only into a promoter-less luciferase reporter vector. When
JEG-3 cells were transiently transfected with this construct and treat
ed with cortisol or its synthetic analogue dexamethasone, a stimulator
y effect on the upstream promoter activity was observed. This stimulat
ion was dependent on the cotransfection of a glucocorticoid receptor (
GR) cDNA expression vector due to the low level of GR in JEG-3 cells a
nd could be completely abolished by RU486, a glucocorticoid antagonist
. Moreover, the cortisol actions could be modulated to a different ext
ent by oestradiol. Thus, since the human placenta contains GRs and the
increase in cortisol metabolism near term is regulated by oestrogen,
the current findings suggest that cortisol may be physiologically invo
lved in the regulation of GnRH gene expression in the human placenta.