Endocrine Abstracts

Volume 6

Society for Endocrinology Medal Lecture

Phil Lowry, School of Animal and Microbial Sciences, University of Reading, Reading, UK Abstract

Professor Phil Lowry is best known for his research on pituitary hormones, corticotrophin-releasing factor (CRF) and the involvement of neuropeptides in pre-eclampsia. A peptide biochemist by training, his preparations of purified corticotrophin (ACTH) and growth hormone (GH) became standards of the World Health Organisation. His close attention to detail is reflected by the fact that the procedures he developed for the large scale purification of therapeutic GH have never been associated with cases of Creutzfeld-Jacob Disease (C-JD) and, in fact, became the method of choice to prepare prion-free pituitary GH. The quality of his methods was noted by Judge Morland in his written report in CJD litigation against the DHS and MRC in the High Court in 1994.

Throughout his career, Professor Lowry has had an uncanny ability to identify and create new areas of research in endocrinology and, when necessary, develop the necessary techniques to advance his research agenda. His work on melanotrophin and ACTH synthesis provided the first evidence of precursor hormone processing before the concept of precursor hormones was even fully developed. His characterisation of CLIP, a fragment of ACTH that is selectively generated in the pars intermedia, enabled him to formulate the concept of tissue-specific processing - several years before its precursor, pro-opiomelanocortin (POMC), was cloned. In trying to understand the significance of this processing, he proposed that adrenal growth was controlled by peptides derived from novel fragments of POMC. When the active peptides could not be generated by any known processing enzymes in the pituitary, he proposed and then proved a new mechanism of activation of endocrine hormones: protease-mediated activation of hormones at the target cell surface. He then cloned and characterised a novel adrenal serine protease that produces a novel adrenal growth factor from the N-terminus of POMC.

As a role model for other endocrinologists, he never let commonly accepted technological limitations restrict his ability to answer fundamental questions. By developing methods to highly purify antibodies, he designed, developed and validated new and sensitive assays to measure hormones in the blood. By developing perfused pituitary cell column systems for the bioassay of hypothalamic hormones, he proved that it was a complex of synergising factors that was responsible for the release of ACTH from the anterior pituitary gland. He later confirmed that synthetic vasopressin and the new CRF fulfilled these roles. He showed that the placenta was capable of secreting significant amounts of CRF into the maternal circulation without any ensuing increase in ACTH or cortisol, a paradox which led him to isolate and clone a specific plasma CRF-binding protein (CRF-BP) that neutralises the biological activity of circulating, but not hypothalamic, CRF. As there was an excess of CRF-BP in the brain, he then predicted that there would be novel CRF-like ligands in the central nervous system and characterised urocortin.

Even today, Professor Lowry continues his search for novel biological hormones. As a result of a long-standing search for an elusive placental neuropeptide responsible for pre-clampsia, he observed that neurokinin B, a tachykinin normally found exclusively in neural tissue, was highly expressed in placenta. He suggested that many of the symptoms characterising pre-eclampsia may be mediated through neurokinin receptor stimulation thereby opening the doors to new drug discovery. The MRC's statement that his observations may constitute a “major breakthrough (in the understanding of pre-eclampsia)” should be extended to much of his past, and undoubtedly future, research. His most recent discovery of a novel tachykinin gene that he has named ‘endokinin’ is a case in point and is likely to open new vistas to explore and investigate.