The dissociation rate of estrogen receptor-ligand complexes is increased by high concentrations of steroids and antiestrogens

• Published in: Molecular and cellular endocrinology Vol. 27; no. 1; pp. 1 - 15
• Main Authors: Borgna, J.L., Ladrech, S.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.1982
• Subjects: Animals; antiestrogen; Cattle; Cold Temperature; Diethylstilbestrol - pharmacology; Dose-Response Relationship, Drug; Estradiol - metabolism; Estrogen Antagonists - pharmacology; estrogen receptor; Female; Gonadal Steroid Hormones - pharmacology; induced dissociation; Kinetics; Rats; Receptors, Estrogen - drug effects; Receptors, Estrogen - metabolism; Sheep; steroid; Uterus - metabolism; cT; TE; antiestrogen; DES; T; estrogen receptor; DCC; E 2; OHT; ER; steroid; induced dissociation
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/0303-7207(82)90058-2

The first-order dissociation rate constant, k_, of estradiol from uterine estrogen receptor, measured in the presence of micromolar concentrations of diethylstilbestrol, increased linearly over a large concentration range (0–300 μM) of diethylstilbestrol. The experimental k_ measured appears to be the sum of a basal dissociation rate constant corresponding to the spontaneous dissociation in the absence of diethylstilbestrol, and a diethylstilbestrol-induced dissociation rate constant, which is proportional to both the diethylstilbestrol concentration and the inverse of the cytosol concentration. Diethylstilbestrol induced the dissociation of estradiol in all species studied (lamb, calf and rat) and of estrone and 2 antiestrogens in lamb uterus. Various steroids and triphenylethylene antiestrogens also efficiently induced the dissociation of estradiol from the estrogen receptor. However, the potency of these inducers, which varied greatly, was not correlated with the binding affinity for the estrogen receptor. Structural characteristics and the hydrophobicity of the inducers, however, did appear to be important parameters. The relative efficiency of inducers varied depending on the ligand that was bound to the receptor. This induced dissociation allows the complete dissociation of estrogen receptor-[ 3H]-ligand complexes in a short time (< 24 h) at low temperatures without alteration of the level of [ 3H]ligand bound non-specifically and can therefore be used to measure the [ 3H]ligand bound to the receptor by exchange at 0–4°C. From the specificity and the high doses of inducers required to make possible the observation of a significant effect, we conclude that the induced dissociation probably does not have a biological role.