Gonadotropin-releasing hormone stimulation of luteinizing hormone release: A ligand-receptor-effector model.

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Abstract
A divalent antibody conjugate of a pure antagonist of gonadotropin-releasing hormone (GnRH) behaved as an agonist-i.e., released luteinizing hormone (LH) from [rat] pituitary cultures. Release was measured over a wide range of conjugate concentrations; it rose to a maximum of 66% of the LH released by the optimal concentration of GnRH and declined to basal levels at very high concentrations. This behavior was modeled on the assumption that the antibody conjugate, A, can react with a receptor, R, to form a complex, A.cntdot.R, which in turn can react with another receptor to form A.cntdot.R2. This dimer then can react with a quiescent effector, E (e.g., a closed Ca2+ ion channel), to form A.cntdot.R2.cntdot.E, which contains activated effector and leads to cellular responses. The equilibrium equations governing the behavior of this model were derived, solved and found to yield a good fit to the experimental data. Consideration of the data in this model system, and of other available data describing the behavior of ligands in other cells, suggests that the present model may be of wide applicability.