Presence of a putative steroidal allosteric site on glycoprotein hormone receptors

Autor: Lorenzo Di Bari, Patrizia Agretti, E. Ferrarini, Tommaso Simoncini, Roberto Maggio, Elena Silvano, Massimo Tonacchera, Antonio Dimida, Giuseppina De Marco, Franco Giorgi, Gabriella Aloisi, Mario Rossi
Rok vydání: 2009
Předmět:
endocrine system
medicine.medical_specialty
Growth-hormone-releasing hormone receptor
Drug Evaluation
Preclinical
Estrogen receptor
Receptors
Cytoplasmic and Nuclear
Thyrotropin
CHO Cells
Chorionic Gonadotropin
Cell Line
DDT
Thyroid hormone receptor beta
Structure-Activity Relationship
Cricetulus
Internal medicine
Cricetinae
Chlorocebus aethiops
medicine
Cyclic AMP
Animals
Receptor
Diethylstilbestrol
Estrogen receptor beta
Pharmacology
Thyroid hormone receptor
Dose-Response Relationship
Drug
Estradiol
Chemistry
Estrogens
Receptors
Thyrotropin
Receptors
LH
Rats
Inbred F344
Rats
Isoenzymes
Endocrinology
Receptors
Estrogen
Hormone receptor
COS Cells
Estrogen-related receptor gamma
Quercetin
Steroids
hormones
hormone substitutes
and hormone antagonists
Allosteric Site
Adenylyl Cyclases
Protein Binding
Zdroj: European journal of pharmacology. 623(1-3)
ISSN: 1879-0712
Popis: In a previous work we found that the insecticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), inhibits the accumulation of cAMP as induced by the bovine thyroid stimulating hormone (bTSH) in cells transfected with the TSH receptor. In this work, we demonstrate that the DDT molecular analogues, diethylstilbestrol and quercetine, are more potent inhibitors of the TSH receptor activity than DDT itself. The notion that all these compounds interfere with nuclear estrogen receptors, as either agonists (DDT and diethylstilbestrol) or antagonists (quercetin), prompted us to test the ability of the steroid hormone 17-beta-estradiol to inhibit the TSH receptor activity. We found that estrogen exposure causes a modest but significant inhibition of the bTSH induced cAMP accumulation both in transfected CHO-TSH receptor and Fischer Rat Thyroid Low Serum 5% (FRTL-5) cells. When applied to CHO cells transfected with the luteinizing hormone receptor, 17-beta-estradiol proved capable of inhibiting the hCG induced cAMP accumulation at a concentration as low as 10nM, though the effect was not greater than 35%. The effect of 17-beta-estradiol was not estrogen receptors mediated, as co-transfection of the estrogen receptor alpha and beta subunits with LH receptor caused cAMP to increase above the level attained by the sole hCG stimulation, and not to decrease it as expected. These data suggest the presence of a steroidal-like allosteric binding site on glycoprotein hormone receptors.
Databáze: OpenAIRE
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