Binding of gonadotropin-releasing hormone (LH-RH) to the pituitary plasma membranes and the problem of adenylate cyclase stimulation.

Specific binding studies of tritium-labeled LH-RH to sheep anterior pituitary membranes at 37 degrees C showed a maximum of binding capacity of 110 +/- 20 mol/mg protein with an association rate constant of 2 +/- 1 X 10(5) M-1 S-1 and a dissociation rate constant of 0.7 +/- 0.4 X 10(-2) S-1. The Scatchard plot data showed a single type of binding site with Kass = 1.1 +/- 0.4 X 10(8) M-1 in good agreement with the kinetic studies. Various doses of LH-RH in the presence or absence of Ca2+, were unable to stimulate adenylate cyclase either in the rat anterior pituitary homogenates, or in the purified sheep anterior pituitary plasma membranes. To explain these results, it may be argued that the proportion of gonadotrophs in the pituitary gland is too small to show a significant increase in the LH-RH-induced adenylate cyclase activity. Another possibility is the disconnection of the hormonal receptor from the site of activation of adenylate cyclase during the preparation of plasma membranes. Finally, cAMP may not be involved in LH release by LH-RH.