Enzymic inactivation of hypothalamic regulatory hormones.

The considerable expansion in studies on the enzymic inactivation of thyrotrophin-releasing hormone, luteinizing hormone-releasing hormone and somatostatin (growth hormone release-inhibiting hormone) has necessitated a re-evaluation of the peptidase enzymes responsible. Through the use of new methods such as high-performance liquid chromatography and the development of artificial enzyme substrates, it has been possible to clarify the mechanisms of enzyme cleavage of these hypothalamic regulatory hormones and to attempt purification of the peptidases. This has brought about a renewed interest in the physiological significance of the enzymes, as well as their role in biotransformation of the hypothalamic hormones. From such studies, the information gained may be used in the design of agonist and antagonist analogues, as well as providing details of the mechanisms of action of such analogues through their increased stability to enzymic degradation. The characterization of corticotrophin-releasing factor and growth hormone-releasing factor will provide a new field for the application of peptidase inactivation to analogue design. Similarly, future examination of the peptidases inactivating the hypothalamic hormones in certain clinical conditions may give new insight into the significance of the enzymes in pathological conditions. Identification of these enzymes, investigation of their localization, properties and functions and assessment of their contribution to the control of hormone action may yield valuable insight into the physiology and pathology of the hypothalamic regulatory hormones.