Receptor-binding Affinities and Biological Activities of Analogs of Thyrotropin-releasing Hormone in Prolactin-producing Pituitary Cells in Culture

Thyrotropin-releasing hormone (TRH) is a hypothalamic tripeptide with the structure l-pyroglutamyl-l-histidyl-l-prolinamide. TRH stimulates prolactin and decreases growth hormone production by GH3 cells, a clonal strain of rat pituitary cells grown in culture. TRH binds to specific receptors on GH3 cells. The activities of 26 analogs of TRH have been measured with the GH3 cell system. Both biological activity (prolactin stimulation and growth hormone depression) and affinity for the TRH receptor have been determined for each peptide. The biological activities of the analogs varied over more than a 10,000-fold range. Biological potency correlated with affinity for the TRH receptor for each peptide. The maximum activity of each active analog was the same as that of TRH. The effects of TRH and TRH analogs on prolactin and growth hormone appeared to involve binding to the same receptor. The TRH receptor on GH3 cells is highly selective, particularly for the COOH-terminal prolinamide of TRH. The prolactin-stimulating activities of analogs closely parallel their thyrotropin-releasing activities, suggesting that the TRH receptors on lactotrophs and thyrotrophs are similar or identical.