Comparison between the interaction of steroids with [35S]TBPS binding to cerebral cortical and to pituitary membranes: correlation with inhibition of prolactin release.
It has been shown previously that 5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha P) can inhibit prolactin release from anterior pituitary gland cells in culture through an interaction with a specific modulatory site on the GABAA receptor complex in anterior pituitary gland membranes. In the present work, this receptor site has been labelled with [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to enable a study of the relative binding affinities (RBA) of different steroids for the GABAA receptor complex to be made. We have found a high correlation (r = +0.88) between the inhibition of [35S]TBPS binding to anterior pituitary membranes and the inhibition of [35S]TBPS binding to cerebral cortical membranes by nine different steroids. There was also a high correlation between the inhibition of prolactin release from anterior pituitary gland cells in culture by these steroids and the inhibition of [35S]TBPS binding to anterior pituitary membranes (r = +0.99) or to cortical membranes (r = +0.81). These observations suggest that the measurement of prolactin release from anterior pituitary gland cells in culture is a good indicator of the functional activity of drugs that bind to the allosteric modulatory TBPS-binding site on the GABAA-receptor complex.
Vincens
M
M
Pharmacologie Endocrinienne, Hospital Lariboisiere, Paris, France.
Shu
C
C
Fortin
M
M
Philibert
D
D
Gaillard-Moguilewsky
M
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*
D011963:Receptors, GABA-A; D013256:Steroids; C041598:t-butylbicyclophosphorothionate receptor; D011388:Prolactin