User:Pruethorner/sandbox

Early Life

Michael Oliver Thorner was born in January 1945 in Beaconsfield, Buckinghamshire, in the United Kingdom. His parents, Dr. Hans A. Thorner, who was a Kleinian psychoanalyst, and his mother Ilse, who practiced as an ophthalmic optician, fled Germany in 1933 and settled in Britain. He attended Merchant Taylor's school and went from there directly to Middlesex Hospital Medical School in London. He graduated in 1970 with honors in Therapeutics and Applied Pharmacology and a prize in Orthopedics.

Career

At the Middlesex Hospital he came under the influence of Sir John Nabarro, a noted British endocrinologist, and went on to completed his fellowship training in endocrinology and metabolism at St. Bartholomew's Hospital in the City of London. There he joined a research group and worked with Professor G. Michael Besser and colleagues on prolactin. The group worked on a specific inhibitor of prolactin secretion that had been developed by Professor Edward Flueckiger of Sandoz (now Novartis) in Basel. At that time it was not known how bromocriptine, the compound developed by Dr. Flueckiger, inhibits prolactin secretion. At the University of Virginia, Dr. Robert MacLeod's pioneering work showed that dopamine is the hypothalamic factor inhibiting prolactin release. Michael Thorner visited Dr. MacLeod at the University of Virginia in 1975, and soon after he was recruited to join the faculty in the University's School of Medicine in 1977.

Research

Michael Thorner continued his research on neurohormonal mechanisms of disease and continued the work he had participated in in England of the use of dopamine agonist drugs in patients with prolactin-secreting pituitary tumors to restore normal prolactin levels and normal gonadal function. This treatment also resulted in cessation of galactorrhea. He pioneered the use of bromocriptine to reduce the size of prolactin-secreting tumors, which for the first time enabled patients to avoid having pituitary surgery. Due to his research, medical treatment with bromocriptine and later other dopamine agonists instead of surgery has become the standard of care for patients with pituitary tumors. Subsequently Thorner and his colleagues were able to clone the GHRH receptor. Thorner and colleagues demonstrated that synthetic GHRH could stimulate growth hormone secretion and growth in growth hormone deficient children.

Together with Dr. Cyril Bowers at Tulane University, he demonstrated that the GH-releasing peptide, a synthetic hexapeptide, which acts through a novel and distinct receptor, acts synergistically with GHRH. They were able to show that this compound could stimulate pulsatile GH secretion, and this was the basis for Merck Research Laboratories' choice of a long-acting spiropiperidine analog for human studies. Thorner and colleagues then showed that GH secretion in the elderly can be stimulated in a physiologic, pulsatile fashion with a single daily dose of this GH secretagogue known as MK-677. This finding opened the door to the restoration of growth hormone in elderly people at a level similar to that seen in young adults. Based on the results of this work, Michael Thorner has obtained a use patent for growth hormone secretagogues in the treatment of loss of muscle mass in the elderly, known as sarcopenia, which contributes to frailty, and is associated with bone fractures, which may in turn lead to premature death of otherwise healthy elderly people. The natural ligand for the growth hormone secretagogue receptor which was cloned by Andrew Howard and colleagues at Merck was shown to be ghrelin, a 28 amino acid peptide produced in the stomach and gastrointestinal tract which has a unique acylation with octanoate at serine which is residue 3. Thorner and colleagues developed two-site sandwich assays to enable study of acyl- and desacyl ghrelin