Desensitization of thyrotrophin-releasing hormone (TRH)-induced growth hormone secretion in chickens: coincident down-regulation of TRH binding to pituitary membranes.

Release of GH is stimulated by TRH in chickens. However, for 60 min following a priming injection of TRH, a second injection of TRH is unable to provoke further GH release. TRH binds to the plasma membranes of the pituitary caudal lobe, in which somatotrophs predominate, although the magnitude of [3H]3-methyl-histidine2-TRH ([3H]Me-TRH) binding was reduced (by 25-50%) 30 min after the i.v. administration of a dose of TRH (5 micrograms/kg) maximally effective in provoking GH release. A significant reduction in [3H]Me-TRH binding to caudal lobe membranes was also observed within 15 min of TRH administration and was maintained for at least 60 min. Control levels of [3H]Me-TRH binding were restored 2 h after TRH injection, coincident with the restoration of GH responsiveness to TRH challenge. The suppression of [3H]Me-TRH binding to pituitary membranes 30 min after in-vivo TRH administration was dose related, whereas the maximal (10 min) GH response to TRH was biphasic. The suppression of [3H]Me-TRH binding to chicken pituitary membranes was due to direct pituitary actions of TRH and could be induced by a 30-min exposure to 100 nM TRH in vitro. These results demonstrate that avian pituitary TRH-binding sites differ greatly from mammalian ones in the timing of the onset and duration of down-regulation. Pituitary TRH-binding sites in birds are rapidly and transiently down-regulated following TRH administration in vivo, coincident with the period of GH refractoriness to TRH challenge.