Abstract
Rats bearing hypothalamic lesions were used as recipients in an in vivo bioassay to measure the content of corticotrophin-releasing factor (CRF) in crude acid extracts of rat hypothalamus. These lesions consistently abolished the increase in plasma corticosterone after ether stress. In the bioassay, the plasma corticosterone level after the iv injection of extract (experimental) was compared with that after ether stress (control) in the same lesioned recipient. In the original procedure, lesioned recipients were ether stressed (48 hours postoperatively) and a control blood sample was withdrawn IS minutes later. Immediately thereafter, extract was injected and the experimental sample obtained 20 minutes later. Injection of vehicle or extracts of cerebral cortex or liver produced little, if any, increase in the experimental corticosterone level, whereas equivalent amounts of hypothalamic extract evoked marked elevations in plasma corticosterone. This response could not be attributed to ACTH contamination in the extract and was suggestive of a CRF effect. However, when increased amounts of nonhypothalamic tissue were administered, highly significant increases in plasma corticosterone were observed. To examine whether ether stress and blood sampling which immediately preceded extract injection were involved in the nonspecific breakthrough of blockade, the assay was modified to avoid these prior manipulations of the recipient. In the modified procedure, the control blood sample was obtained 24 hours postoperatively and at 48 hours, extract was injected (without prior manipulation) and the experimental sample taken. Under these conditions, the nonspecific responses were eliminated, whereas increasing doses (over a 4-fold range) of hypothalamic extract evoked significant (dose-related) increases in plasma corticosterone. The data suggest that lesioned rats can, under certain conditions, be sensitized so that rapid pituitaryadrenocortical responses can be evoked by nonhypothalamic tissue extracts. A necessary condition for a reliable in vivo CRF bioassay is to avoid prior sensitization of the lesioned recipient. {Endocrinology 90: 552, 1972) r P H E concept of hypothalamic control of -*• ACTH release has received firm support as a result of numerous reports of impaired pituitary-adrenal function in animals bearing hypothalamic lesions (1-4). Since stress-inReceived March 24, 1971. Supported by USPHS Grant AM-11496 from the National Institute of Arthritis and Metabolic Diseases. 1 The material presented herein was taken from a dissertation submitted to the Graduate School of Yale University by R. J. Witorsch in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Physiology. 2 Present address Department of Physiology, Medical College of Virginia, Health Sciences Division of Virginia Commonwealth University, Richmond,
Published Version
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