Endocrine Abstracts

The discovery of GnRH involved extraordinary insight, determination and creativity as well as conflict and competition where the players inadvertently advanced each other’s endeavours. However, many of us experienced great collegiality, collaboration and sharing reagents in these halcyon years. Many colourful and ambitious characters were involved in the recognition that a portal system transferred a factor from the brain to the pituitary supported by elegant experiments by Harris against vitriolic counter argument from the powerful Zuckerman. The purification of GnRH and TRH involved a tour de force and furious competition between Schally in New Orleans and Guillemin at the Salk Institute. The task involved purification from millions of brains, an effort never again matched as technical advances and the genomic era eased the task. Synthesis of GnRH and structure/activity studies yielded the production of agonists and antagonists and heralded an impressive acceleration of basic and clinical sciences and unprecedented novel treatments for diverse diseases. Basic GnRH research advanced hand in hand with clinical research. The discovery that pulsatile GnRH was stimulatory of gonadotropin but continuous was inhibitory gave rise to treatment for hormone-dependent diseases such as prostate cancer and other conditions. We are now in the era of GnRH antagonists which have immediate inhibition and can be dosed via non-peptide orally active antagonists. A new era emerged with my lab’s discovery that there were many variants of GnRH and importantly that one of these, GnRHII was conserved in all vertebrates and was involved in reproductive behaviours. We also succeeded in the cloning the GnRH receptor which accelerated the development of new analogues. The wide distribution of GnRH and cognate receptor in the brain suggested that it had diverse functions, including sexual behaviour and appetite and this year saw the discovery that pulsatile GnRH improves cognition in Down syndrome.