Corticotropin-Releasing Factor*

It is shown that stress-induced activation of the central nervous system is transduced from a neural into a humoral signal in the hypothalamus, and chemical transmitter substances elaborated are transported to the adenohypophysis via the hypophyseal portal circulation to stimulate the secretion of ACTH from the corticotrophs.

Abstract

IN 1948 Geoffrey Harris (1) hypothesized that stress-induced activation of the central nervous system is transduced from a neural into a humoral signal in the hypothalamus. Resultant chemical transmitter substances elaborated are transported to the adenohypophysis via the hypophyseal portal circulation to stimulate the secretion of ACTH from the corticotrophs. Despite intensive studies by many investigators throughout the world in the intervening years, identification of this putative neurotransmitter has been extremely difficult. Slusher and Roberts (2) were the first to describe ACTH-releasing activity in a hypothalamic extract. Unfortunately, the assay using intact, untreated rats employed in their experiments was inadequately refined (2, 3) since such animals will secrete ACTH in response to a variety of nonspecific stresses. In 1955 more specific experimental evidence for the existence of a brain extract that stimulated ACTH secretion was independently presented by Saffran and Serially (4) and Guillemin and Rosenberg (5). The former group named the putative material corticotropin-releasing factor (CRF). Although this appellation may be unfortunate in some respects, especially since CRF probably stimulates both formation and secretion of ACTH, it is “catchy” and provides a useful mnemonic handle. It has not only survived to the present but has spawned the generic term of “releasing factor” or “releasing hormone” for many hypothalamic materials with hypophysiotrophic activity.