Significance and Function of Neuropeptides in Cerebrospinal Fluid

Abstract

Although the mammalian anterior pituitary gland lacks a direct nerve supply from the brain, it is now well established that the central nervous system (CNS) exercises control over the secretion of each adenohypophyseal hormone through “releasing factors” synthesized and secreted by peptidergic neurons in the hypothalamus.13,85 As postulated over 30 years ago (”portal vessel chemotransmitter hypothesis”), the hypothalamus secretes into the portal capillaries of the median eminence (ME) specific pituitary regulatory substances that are transported to the anterior pituitary by the portal vessels of the pituitary stalk47 (see Fig. 1). The isolation and synthesis of three of these hypothalamic hypophy-siotropic hormones, thyrotropin-releasing hormone (TRH), luteinizing-hormone-releasing hormone (LH-RH), and growth-hormone-release-inhibiting hormone (somatostatin) (Fig. 2), have provided powerful tools for the investigation of hypothalamic-pituitary function and have permitted the development of specific radioimmunoassays for the measurement of these substances at low concentrations.120,153 An unanticipated outcome of these methodological developments was the finding that most of neural TRH and somatostatin are located in regions of the CNS outside the hypothalamus.59,60 Even more surprising was the discovery that both TRH60,86 and somatostatin are present in anatomical locations outside the nervous system altogether. Further, these hypothalamic hormones are present in primitive species wherein no pituitary occurs.61 The functional significance of the widespread phylogenetic distribution is not known for sure, but it has been postulated that these substances may initially have evolved as primitive neurotransmitters or modulators of neurotransmission and that only late in evolution did they acquire the function of regulating anterior pituitary hormone secretion.60