Presence of a putative steroidal allosteric site on glycoprotein hormone receptors.


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.

DOI: 10.1016/j.ejphar.2009.09.029

Cite this paper

@article{Rossi2009PresenceOA, title={Presence of a putative steroidal allosteric site on glycoprotein hormone receptors.}, author={Mario Rossi and Antonio Dimida and Eleonora Ferrarini and Elena Silvano and Giuseppina de Marco and Patrizia Agretti and Gabriella Aloisi and Tommaso Simoncini and Lorenzo Di Bari and Massimo Tonacchera and Franco De Giorgi and Roberto Maggio}, journal={European journal of pharmacology}, year={2009}, volume={623 1-3}, pages={155-9} }