COMPARISON BETWEEN THE INTERACTION OF STEROIDS WITH [S-35] TBPS BINDING TO CEREBRAL CORTICAL AND TO PITUITARY MEMBRANES - CORRELATION WITH INHIBITION OF PROLACTIN-RELEASE

It has been shown previously that 5alpha-pregnan-3alpha-ol-20-one (5alpha3alphaP) can inhibit prolactin release from anterior pituitary gland cells in culture through an interaction with a specific modulatory site on the GABA(A) receptor complex in anterior pituitary gland membranes. In the present work, this receptor site has been labelled with [S-35]t-butylbicyclophosphorothionate ([S-35]TBPS) to enable a study of the relative binding affinities (RBA) of different steroids for the GABA(A) receptor complex to be made. We have found a high correlation (r = +0.88) between the inhibition of [S-35]TBPS binding to anterior pituitary membranes and the inhibition of [S-35]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 [S-35]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.