Comparison between the interaction of steroids with [35S]TBPS binding to cerebral cortical and to pituitary membranes: correlation with inhibition of prolactin release

Summary It has been shown previously that 5-pregnan-3-ol-20-one (53P) 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 GABA_A-receptor complex.Correspondence to M. Vincens at the above address