Peptide hormones, neuropeptides, neurotransmitters and other non-steroid chemical messengers stimulate biochemical activity by binding to receptors on the plasma membranes of their target cells. These chemical messengers cannot enter their target cells to stimulate the nucleus in the manner described for steroid and thyroid hormones in Chapter 9. In order to activate biochemical changes within the target cell, they act as first messengers to activate a second messenger, such as cyclic adenosine monophosphate (cyclic AMP), within the cytoplasm of the target cell. The transduction of information from the first to the second messenger is accomplished through the activation of membrane protein transducers (G-proteins) and enzymes, such as adenylate cyclase. This chapter examines the membrane receptors for peptide hormones and neurotransmitters, the mechanisms by which signal transduction across the cell membrane occurs, the role of G-proteins in this signal transduction, the second messenger systems activated, and the actions of the second messengers in the target cells, with special emphasis on neural target cells.

MEMBRANE RECEPTORS

The membrane receptors are complex glycoproteins embedded in the cell membrane. The function of these receptors is to recognize specific ligands in the blood (e.g. peptide hormones, neuropeptides) or in the synapse (e.g. neurotransmitters) and bind to them. Once this binding occurs, signal transduction across the cell membrane occurs as described in Section 10.2 below. Using a number of pharmacological and biochemical techniques employing radioactively labeled ligands, fluorescent dyes, affinity chromatography and immunochemical identification, it is possible to discover the location and structure of the membrane receptors (see Limbird, 1986; Yamamura, Enna and Kuhar, 1990).

HORMONES, THE BRAIN AND BEHAVIOR

Research on hormones and the brain covers many fields: from cell biology and genetics to anatomy, physiology, pharmacology, medicine and psychology. This book will examine the interactions between hormones, the brain and behavior. The main focus will be on how the endocrine and nervous systems form an integrated functional neuroendocrine system which influences physiological and behavioral responses.

When you hear the term ‘hormone’, you think of the endocrine glands and how their secretions influence physiological responses in the body. That is, however, merely the beginning of the picture. Many of the endocrine glands (although not all of them) are influenced by the pituitary gland, the so-called ‘master gland’, and the pituitary is itself controlled by various hormones from the hypothalamus, a part of the brain lying above the pituitary gland. The release of hypothalamic hormones is, in turn, regulated by neurotransmitters released from nerve cells in the brain. Neurotransmitters also control behavior and the release of neurotransmitters from certain nerve cells is modulated by the level of specific hormones in the circulation. Thus, neurotransmitter release influences both hormones and behavior and hormones influence the release of neurotransmitters. This interaction between hormones, the brain and behavior involves a wide variety of chemical messengers, which are described in this chapter.

This chapter provides an introduction to the chemical messengers found in the neuroendocrine system. Later chapters describe the endocrine glands and their hormones (Chapter 2), the pituitary gland and its hormones (Chapter 3) and the regulation of the pituitary gland by the hypothalamic hormones (Chapter 4).

Behavioral neuroendocrinology involves the study of the interactive effects of the steroid and peptide hormones, neuropeptides, cytokines and neurotransmitters on behavior. Previous chapters have mentioned the role of the hypothalamic nucleii in behavior (Section 4.1), the behavioral effects of neurotransmitter agonists and antagonists (Section 5.8), the neuroendocrine correlates of psychiatric disorders (Section 6.8), the behavioral functions of the steroid hormones (Section 9.9), the cognitive and behavioral effects of neuropeptides (Section 12.5), and the effects of the cytokines on the brain and behavior (Section 13.5). This chapter discusses the behavioral methods used for the study of neuroendocrinology, the neural and genetic mechanisms mediating the effects of hormones on behavior, and some of the special problems involved in conducting behavioral neuroendocrinology research.

Neuroendocrine research involves a number of specific methods such as radioimmunoassays (Chapter 8), autoradiography (Chapter 9), receptor binding assays (Chapter 10) and immunohistochemical techniques (Chapters 11 and 13). The study of behavioral neuroendocrinology relies on specific behavioral methodologies or behavioral bioassays. As discussed in Section 8.1, a bioassay measures physiological changes in an animal or cell culture to determine the concentration or potency of a hormone in the circulation. Thus, the size of a cock's comb is a bioassay for testosterone level and the size and weight of the adrenal glands are bioassays for the level of ACTH. A behavioral bioassay measures behavioral changes to determine the concentration or potency of a hormone.

BEHAVIORAL BIOASSAYS

A behavioral bioassay requires precise qualitative (verbal) descriptions of the behaviors of interest and accurate quantitative (mathematical) measures of the latency, frequency and duration of these behaviors.

This book is an introduction to neuroendocrinology from the point of view of the behavioral neurosciences. It is intended for students in Psychology, Biology, Nursing, Health Education, and other fields of Arts and Science and for more advanced students in physiology, anatomy and medicine who have not had a course on neuroendocrinology. It is based on the first half of my Hormones and Behavior lectures at Dalhousie University. While my lectures, and thus the book, focus primarily on mammalian research, the principles outlined apply to all vertebrates.

This book provides an outline of the neuroendocrine system and will give you the vocabulary necessary to understand the interaction between hormones and the brain. This information is essential to the understanding of the effects of hormones on behavior, but contains little reference to behavior until Chapter 14. In fact, it contains mainly endocrinology, physiology and a bit of cell biology, immunology and biochemistry. Do not despair. Once you master this material, the study of how hormones influence developmental processes and behavior will be easier to understand. This book focuses primarily on the neural actions of hormones, so many of the peripheral physiological actions of hormones, such as regulation of metabolism, water balance, growth, and the regulation of calcium, sodium and potassium levels, which are the focus of traditional endocrinology texts, are referred to only in reference to their importance in the neuroendocrine system.

THE AIM OF THIS BOOK

The aim of this book is to teach students the language and concepts of neuroendocrinology with an emphasis on how the neuroendocrine system influences behavior. It began with a classification of chemical messengers in the body as ‘true’ hormones, neurohormones, neurotransmitters, pheromones, parahormones, prohormones, growth factors and neuroregulators. As more became known about the neuroendocrine system, it was seen that these classifications are not clear cut and a single chemical could fit into two or more classes of messenger. While the classification of chemical messengers is useful to begin the study of neuroendocrinology, by the end it provides little help in understanding the different actions of peptides, steroids and neurotransmitters on different target cells.

The endocrine glands and the pituitary gland are generally thought to be the basis of the neuroendocrine system, but the traditional endocrine function of hormones acting on peripheral target cells provides only a small part of the neuroendocrine activity of a hormone such as testosterone, cholecystokinin or prolactin. These hormones also have significant effects on neural receptors and alter neural regulation of autonomic reflexes, behavior and emotional states. The hypothalamus provides the link between the traditional endocrine system and the brain and provides the mechanism for external factors to regulate the endocrine system. Thus, while the endocrine system appears to consist of a number of closed-loop feedback systems, with highly regulated physiological control over the synthesis, storage, release and deactivation of hormones, external stimuli can alter these systems. Environmental stimuli, social interactions and cognitive factors can greatly alter the functioning of the endocrine system by altering the ‘classical’ neurotransmitter pathways which regulate the release of hypothalamic hormones.