Dynamic model of gonadotropin-releasing hormone receptor function.

Abstract

Functioning gonadotropin-releasing hormone (GnRH) receptor is visualized as an aggregate of identical subunits (not all always functional) with the aggregate usually transformed into at least four successive structurally distinct receptor assemblies. Receptor protein, hormone molecule(s), and carrier(s) are main components of each functional subunit. During the normal lifespan of the functional subunit, each carrier is responsible for delivery of a unit amount of product, per unit time, to the cell surface (ratio between functional carrier and bound hormone, 1:1). Association of hormone with the receptor protein is essential, not only for the initial formation of the functional subunits but also for subsequent conformational changes that are in turn essential for formation of the aggregate only, or later (in the presence of sufficiently high GnRH concentrations) for a successive formation of a family of receptor assemblies (occurring one at a time). The successive assemblies differ from the aggregate by being more stable and from one another by increasing GnRH binding affinity and apparent capacity. They resist stimulation during protracted decay (desensitization).