Human progesterone receptor shows differential sensitivity to carboxyl group modifying agents when bound to agonist and antagonist ligands.
BACKGROUND
Modulation of human uterine progesterone receptor (PR) in relation to its binding to synthetic steroids with known agonist (R5020) and antagonist (triamcinolone acetonide, T.A.) properties was studied in the presence of the specific carboxyl group modifiers, N,N'-dicyclohexylcarbodiimide (DCCD) and 1-ethyl-3-carbodiimide hydrochloride (EDC).


METHODS
Uterine cytosol was treated with DCCD or EDC. The amounts of total bound were detected using the steroid binding measurements. The formation and transformation of progesterone-receptor complexes (PRc) were analyzed using sedimentation rate analysis.


RESULTS
Our studies show that the modification of the COOH group differentially influences the properties of mammalian PR binding with either R5020 or T.A. DCCD and EDC affect the steroid binding of PR by decreasing the binding sites, not by the changing the affinity.


CONCLUSIONS
Our studies indicate the importance of the carboxyl group in steroid binding by PR. This implies that both aspartic acid and glutamic acid residues, which have the carboxyl group, may play an important role when PR binds with steroid ligands.
Wu
C M
CM
Department of Surgery, Chang Gung Memorial Hospital, 5, Fu-Shin Street, Kweishan, Taoyuan, Taiwan, R.O.C. chimingwu@.cgmh.org.tw
Liu
T J
TJ
Huang
C C
CC
Hwang
T L
TL
Pan
R L
RL
D003600:Cytosol / Q000378:metabolism; D004024:Dicyclohexylcarbodiimide; D005260:Female; D006801:Humans; D008024:Ligands; D045167:Progesterone Congeners; D011397:Promegestone; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014222:Triamcinolone Acetonide; D014599:Uterus / Q000737:chemistry
D008024:Ligands; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; D004024:Dicyclohexylcarbodiimide; D011397:Promegestone; D014222:Triamcinolone Acetonide