Glucocorticoids modulate human gonadotrophin releasing hormone upstream promoter activity in transfected human placental cells (JEG-3).
A human gonadotrophin releasing hormone (GnRH) upstream promoter/luciferase reporter gene construct (H2 construct) was generated by inserting a 1.7 kb XbaI/AflII fragment containing the human GnRH upstream promoter region only into a promoter-less luciferase reporter vector. When JEG-3 cells were transiently transfected with this construct and treated with cortisol or its synthetic analogue dexamethasone, a stimulatory effect on the upstream promoter activity was observed. This stimulation was dependent on the cotransfection of a glucocorticoid receptor (GR) cDNA expression vector due to the low level of GR in JEG-3 cells and could be completely abolished by RU486, a glucocorticoid antagonist. Moreover, the cortisol actions could be modulated to a different extent 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 involved in the regulation of GnRH gene expression in the human placenta.
Chen
Z G
ZG
Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk 23507, USA.
Chou
C S
CS
Hsu
M I
MI
Dong
K W
KW
D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D015735:Mifepristone / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins; D014162:Transfection
D005938:Glucocorticoids; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D003907:Dexamethasone; D008156:Luciferases; D006854:Hydrocortisone