Our objectives are (1) to complete our identification of the biosynthetic origin of two TRH-like peptides which we first identified in human seminal fluid (2) to extend our knowledge of their physiological roles and (3) to identify factors involved in the regulation of their activity. The actions of pGlu Glu Pro amide are consistent with a role in fertility and we propose to study these two peptides in, and their action on, infertile males. The two peptides also exhibit central activities, some in common with benzodiazepines, and we will study these at the molecular level. During our studies of TRH-like peptides in the thyroid gland, we found that marmoset and human thyroid contain high concentrations of authentic TRH, together with a TRH-like peptide, suggesting a functional role for the thyroidal TRH. We also find that the levels of TRH in rat thyroid reflect the thyroid status; we intend to investigate the mechanisms involved. We are also developing a reliable method for the determination of TRH and TRH-like peptides in the circulation which will have clinical application.