Recent research demonstrated that endocrine actions of thyrotropin (TSH)-releasing hormone (TRH) are modulated by gene-related products within proTRH. In the present report we show that the growth hormone (GH) response to TRH is clearly inhibited after the preincubation of chicken pituitary glands with preproTRH((160-169)) Ps4, whereas the TSH response is not impaired. Binding sites for I-125-[Tyr(0)]-Ps4 were, however, not detected on chicken pituitary membranes, although (as a control) they were readily detectable on membranes from rat pituitary glands. An indirect action may therefore take place within the pituitary by modulating the action of somatostatin (SRIH), the inhibitor of GH release in the chicken. This hypothesis is strengthened by the observation that Ps4 increases the binding of I-125-[Tyr(1)]-SRIH to chicken pituitary membranes in a dose-related way. Since Ps4 is also produced by pituitary tissue, this may reflect a local or paracrine action on the regulation of GH release. (C) 2000 Harcourt Publishers Ltd.