It had been known from the work of McCann (1960) and of Campbell and co-workers (1964) that extracts of hypothalamic tissue contain a biologically active substance capable of stimulating the release of gonadotrophic hormones from the pituitary. This material was isolated from the hypothalami of stockyard animals, and the structure was finally elucidated by Schally's group in 1971. Like TRH, the amino terminal of GnRH is a substituted amide. A terminal amide group is characteristic of a number of other small peptide hormones, including ADH, oxytocin, calcitonin, gastrin, and glucagon; in all of these hormones (including TRH and GnRH), the amide group is needed for full hormonal activity.
