The concept of neurosecretion probably had its origins in the observations of Speidel, in 1919, who noted that some hypothalamic neurons had the morphologic characteristics of glandular cells. That idea, which is now viewed as a fundamental part of the science of endocrinology, was so novel that it was rejected by most biologists at the time. The expansion of knowledge of neuroendocrinology during the past century stands as one of the significant achievements in neurobiology. It is now well established that neurons, in addition to transmitting electrical impulses, can synthesize and secrete complex molecules locally and into the systemic circulation, and that these molecules are capable of stimulating or inhibiting endocrine, renal, and vascular cells at distant sites.
Following the observations of Spiedel, Euler and
Gaddum made the seminal observation in 1931 that peptides secreted by neurons in the central and peripheral nervous systems were also secreted by glandular cells of the pancreas, intestines, and heart. They isolated a substance from the intestines that was capable of acting on smooth muscle and called it “P” (from powder). But it was not until some 35 years later that Leeman and her associates purified an 11-amnio-acid peptide that is now called substance P (see Aronin et al). Then followed the discovery of six hypothalamic mediators of anterior pituitary hormone secretion: thyrotropin-releasing hormone (TRH), somatostatin, gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and hormone-releasing hormone (GHRH). Throughout this time it was already known that dopamine acted as an inhibitor of pituitary hormone secretion. Subsequently, a number of other neuropeptides including enkephalin, neuropeptide Y, and orexin were discovered, as discussed in Chap. 18.
The hypothalamus lies on each side of the third ventricle and is continuous across the floor of the ventricle. It is bounded posteriorly by the mammillary bodies, anteriorly by the optic chiasm and lamina terminalis, superiorly by the hypothalamic sulci, laterally by the optic tracts, and inferiorly by the hypophysis. It comprises three main nuclear groups: (1) the anterior group, which includes the preoptic, supraoptic, and paraventricular nuclei; (2) the middle group, which includes the tuberal, arcuate, ventromedial, and dorsomedial nuclei; and (3) the posterior group, comprising the mammillary and posterior hypothalamic nuclei.
According to the system proposed by Nauta and Haymaker, the components of the hypothalamus can also be grouped according to their position in the sagittal plane. The lateral part lies adjacent to each fornix; it is sparsely cellular and its cell groups are traversed by the tegmental reticular formation and the medial forebrain bundle. The latter carries finely myelinated and unmyelinated ascending and descending fibers to and from the rostrally placed septal nuclei, substantia innominata, nucleus accumbens, amygdala, and piriform cortex. In contrast, the medial part of hypothalamus is rich in cells, some of which are the neurosecretory cells for pituitary regulation and visceral control. It contains two main efferent fiber systems—the mammillotegmental tract and the mammillothalamic tract of Vicq d’Azyr (named for the physician to Louis XV and XVI, a paramour of Marie Antoinette), which connects the mammillary nuclei with the anterior thalamic nucleus. Additional structures of importance are the stria terminalis, which runs from the amygdala to the ventromedial hypothalamic nucleus, and the fornix, which connects the hippocampus to the mammillary body, septal nuclei, and periventricular parts of the hypothalamus. The lateral and medial parts of the hypothalamus are interconnected and their functions are integrated.