Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.28 (
chloramphenicol acetyltransferase
)
5,100
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Norethisterone
(
NET
) and levonorgestrel (LNG) are synthetic progestins used as contragestational agents. Both compounds are biotransformed at target tissues into A-ring reduced metabolites which possess different pharmacological properties. The aim of this study was to determine the molecular mechanisms of the progestational and antiprogestational effects of
NET
, LNG and their metabolites by using a highly efficient, sensitive in vitro molecular assay based on the detection of a reporter gene expression (the bacterial
chloramphenicol acetyltransferase
(
CAT
) inserted downstream of a minimal promoter containing two progesterone responsive elements (PRE2) and the TATA box. For this purpose we used CV-1 monkey kidney cells, which do not possess steroid receptors. These cells were cotransfected with a progesterone receptor expression vector and the reporter vector PRE2-TATA-
CAT
. Data obtained using this model showed that
NET
and LNG induced
CAT
activity in a manner similar to that of the potent progestin R5020.
NET
and LNG metabolites exhibited a weak progestational activity; however, when 5 alpha-
NET
metabolite was simultaneously administered with R5020, a clear antiprogestational effect similar to that of the antiprogestin RU486 was observed. Therefore, the results clearly demonstrate that the use of the reporter
CAT
vector containing hormone responsive elements is a suitable assay for the screening and evaluation of new synthetic steroids with agonist or antagonist progestational activities in transfected CV-1 cell line.
...
PMID:In vitro molecular assessment of the mechanisms of action of 19-nor progestins used as contragestational agents. 884 51
