The mammalian anterior pituitary was not known to be directly regulated by nervous elements until recently. Although it is generally acknowledged that there are a small number of nerve fibres in the anterior pituitary, they are considered to be autonomic in nature and are not directly involved in the regulation of the activities of the gland cells. 2. A growing body of evidence has been accumulated in the past decade, mainly from our laboratory, indicating that the anterior pituitary can be directly regulated by nerve fibres innervating it. The present article reviews the evidence for the hypothesis that there is neural-humoral dual regulation of the mammalian anterior pituitary. 3. Human, macaque monkey, dog and rat anterior pituitaries have been used for immunocytochemical studies at light and electron microscopic levels. Studies of the changes in the nerve fibres in the anterior pituitary following adrenalectomy or ovariectomy have been conducted on rats. The effects of electrical stimulation of the nerve fibres in the anterior pituitary on adrenocorticotropic hormone (ACTH) secretion have also been studied. 4. There are substantial amounts of nerve fibres in the anterior pituitary. They are in close proximity to the gland cells, including forming synapses. The number of nerve terminals are large. Adrenalectomy or ovariectomy induces an active response of the nerve fibres and electrical stimulation of the nerve fibres changes ACTH secretion. 5. It has been concluded that the anterior pituitary can be directly regulated by the innervating nerve fibres.
