The study shows that giving growth hormone‑releasing hormone (GHRH) or its analogs like sermorelin repeatedly over a short period makes the receptors on pituitary cells less responsive. This desensitisation reduces the amount of growth hormone released, especially when the hormone is given too often or at high doses. The effect is seen both in human‑derived cells and in rat pituitary cells, meaning it likely applies to humans too.

We have investigated the effect of short-term preexposure of growth hormone-releasing hormone (GHRH) on the subsequent response to GHRH in a baby hamster kidney (BHK) cell line expressing the human GHRH receptor and in primary rat pituitary cells. In the BHK cells the receptor was rapidly desensitised in a homologous fashion. Preexposure with agents directly stimulating the cAMP pathway like forskolin and db-cAMP had no effect. In rat pituitary cells we also observed a rapid desensitisation of the GHRH response in an apparently homologous fashion. In both systems the desensitisation was dose-dependent with no change in the potency of the hormone in a subsequent stimulation, only the efficacy was decreased. In the rat pituitary cell, the response 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 desensitised a subsequent growth hormone-releasing hormone stimulation, indicating 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 suggesting a rapid internalisation process. Together, these data indicate that after short-term GHRH preexposure, both in a human and rat system, the following GHRH response is desensitised. In BHK cells this desensitisation is strictly homologous. In rat pituitary cells, on the other hand, the desensitisation is a mixed homologous/ heterologous type.