Current theory of control of anterior pituitary function was foreshadowed by two clinical observations. In 1927, Worster-Drought et al, after describing a case of probable craniopharyngioma, suggested that "the hypothalamic nuclei would appear to control, as it were, the function of the different pituitary lobes." In the 1930s clinicians at the Mayo Clinic2 noted that in patients with functioning unilateral adrenocortical tumors, the other adrenal gland was atrophic and postulated what we now call the "negative feedback control" of corticotropic function.
About 1950 G. W. Harris3 published well-founded arguments that the hypothalamus modulates anterior pituitary function by means of substances carried from the hypothalamus to the anterior pituitary in a hypophysial portal system that originates in the median eminence at the base of the hypothalamus. His argument received strong support in 1955 when Saffran and Schally4 described release of corticotropin (ACTH) from anterior pituitary tissue in vitro