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.