The growth hormone-releasing hormone receptor: Desensitisation following short-term agonist exposure

We have investigated the effect of short-term preexposure of growth hormone -releasing hormone (GHRH) on the subsequent response to GHRH in a baby hams ter kidney (BHK) cell line expressing the human GHRH receptor and in primar y rat pituitary cells. In the BHK cells the receptor was rapidly desensitis ed in a homologous fashion. Preexposure with agents directly stimulating th e cAMP pathway like forskolin and db-cAMP had no affect. In rat pituitary c ells we also observed a rapid desensitisation of the GHRH response in an ap parently homologous fashion. In both systems the desensitisation was dose-d ependent with no change in the potency of the hormone in a subsequent stimu lation, only the efficacy was decreased. In the rat pituitary cell, the res ponse measured as growth hormone release was more sensitive to the agonist- induced desensitisation than the cAMP response. No indication of depletion of growth hormone (GH) stores was seen. In rat pituitary cells, contrary to observations in BHK cells, preexposure with both forskolin and db-cAMP des ensitised a subsequent growth hormone-releasing hormone stimulation, indica ting a heterologous desensitisation. Phorbol-12-myristate 13-acetate (PMA), on the other hand, had no effect. In the baby hamster kidney cells it was demonstrated that the GHRH receptor surface expression decreased following preexposure with GHRH. This phenomenon was observed only in whole cells sug gesting a rapid internalisation process, Together, these data indicate that after short-term GHRH preexposure, both in a human and rat system. the Fol lowing GHRH response is desensitised. In BHK cells this desensitisation is strictly homologous. In rat pituitary cells, on the other hand, the desensi tisation is a mixed homologous/heterologous type.