Seymour Reichlin – författare

The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi­ uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap­ plied in neuronal tissue to the neurohypophysis.

The discovery of hypothalamic factors that inhibited growth hormone secretion and of pancreatic factors that inhibited insulin secretion were the first clues to the existence of somatostatin. During the course of efforts to isolate growth hormone releasing factor, Krulich, McCann and Dhariwal found that hypothalamic extracts contained a potent inhibitor of growth hormone secretion. They postulated that growth hormone secretion was under a dual control system, one inhibitory and the other excitatory (I) . In studies being carried out at about the same time, Hellman and Lernmark found a factor in pancreatic extracts that inhibited insulin secretion (2). They postulated that islet cell function was regulated by local hormonal factors. With the isolation and chemical characterization of somatostatin by Brazeau and colleagues (3), and the availability of relatively large amounts of the synthetic peptide for research, it has been possible to demonstrate that both predictions were true. Subsequent work revealed that somatostatin, as initially isolated (somatostatin 14), was but one of several related peptides, part of a multigene family, with tissue specific processing. Many of the details of biosynthesis and genetic control have been worked out, and this molecule has served many workers as a model gut-brain peptide for detailed study. The peptides are widely distributed in tissues and exert an extraordinary range of effects on most glandular secretions, both internal and external.