Physiological evidence for 'short-loop' feedback effects of ACTH on hypothalamic CRF.

Abstract

Hypothalamic CRF activity in male rats has been measured by an improved pituitary incubation method. A linear log dose-response relationship was obtained between the amount of hypothalamic extract added to the incubation medium and the plasma corticosterone levels of hypophysectomized ACTH assay rats, following injection of the incubation medium. The hypothalamic CRF activity in long-term hypophysectomized rats (1–6 weeks) was 3 to 4 times greater than that found in extracts from intact rats. Hypophysectomy of shorter duration (2–4 days) did not result in a significant change in hypothalamic CRF activity. The CRF activity of extracts of hypothalami from chronically adrenalectomized rats (3–6 weeks) was half of that found in extracts from sham-adrenalectomized controls. Adrenalectomy of shorter duration (1 week) did not result in a significant change in hypothalamic CRF activity. The elevated hypothalamic CRF levels seen in hypophysectomized rats was not altered by subsequent adrenalectomy. Injection of ACTH into hypophysectomized-adrenalectomized rats reduced hypothalamic CRF content to 1/8 the levels found in hypophysectomized-adrenalectomized controls. These results suggest a direct action of ACTH on the hypothalamus, and provide evidence for a ‘short-loop’ feedback system between ACTH and CRF. These findings do not rule out the possibility that adrenal steroids, as well as other factors, may influence the rate of synthesis and/or release of CRF, but they do indicate that circulating ACTH levels may play a significant role in this regulation.