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This chapter examines the role of peptide hormones in the regulation of neural mutability and the involved cellular and molecular mechanisms. It first considers the effects of vasopressin and oxytocin—hormones released in the neurohypophysis. It then analyzes the plastic actions of corticotropin-releasing hormone, prolactin, gonadotropin-releasing hormone, insulin, growth hormone, insulin-like growth factor-I (GF-I), erythropoietin and angiotensin. Finally, the chapter considers the effects of feeding hormones leptin, ghrelin, and glucagon-like peptide-1 on neural plasticity. These hormones exert important plastic actions on the organization of neuronal circuits involved in the control of food intake and energy balance, but also promote plastic remodeling of cognitive brain areas.

This chapter covers peripheral signals for hunger and satiety. Internal regulators of appetite and body weight are described, such as hormones including leptin. Brain mechanisms are explained and the question asked: What make food taste pleasant? Sensory-specific satiety is described. The effect of variety on food intake; the hypothalamus, orbitofrontal cortex, and amygdale; the normal and abnormal control of appetite, including obesity and anorexia, are also covered.

Energy homeostasis, the balance of energy intake, assimilation, expenditure, and storage, is regulated by a distributed network of specialized metabolic sensing neurons that receive viscerosensory afferent input and hormonal and metabolic signals from the periphery. These neurons then activate autonomic pathways controlling physiological functions, metabolism, and hormone secretion. Leptin and insulin levels, which reflect the size of adipose stores, act centrally to inhibit food intake and increase sympathetically-mediated thermogenesis as adipose stores increase when energy intake exceeds expenditure. As stores are depleted during fasting, leptin and insulin promote hunger and food seeking. The effects of leptin and insulin on metabolic sensing neurons are modulated by autonomic afferent, gut hormone and metabolic substrate feedback. This finely controlled regulation of energy and glucose homeostasis is perturbed by the superimposition of obesity and diabetes, particularly in genetically predisposed individuals.

Obesity is an increasing medical problem in Western societies. There is little question that body weight, like many other physical features, is under genetic control. Each person has a genetically determined “set point” weight that is maintained within a narrow range with normal caloric intake. What are the factors that determine the set point? Are genes involved in the behaviors that lead to overeating and undereating that moves the body above or below the set point? Leptin is a normal protein that has a powerful effect on the perception of satiety. Others are being studied for similar effects. Neuropeptide Y also affects appetite. Disorders such as anorexia and bulemia have a strong genetic component, likely through genes and receptors for serotonin, which is also involved in impulsive behaviors and depression.

Trade-offs between reproduction and maintenance can compromise health. Male hormones such as testosterone regulate energy allocation between reproductive effort and survival; this is made evident when immunological challenges cause changes in reproductive hormones. Female hormones adjust energy allocation between investment in ovarian function, somatic investment, and present offspring (lactation), implementing trade-offs between present and future reproduction. Metabolic hormones respond to environmental cues to sequester or liberate energetic resources such as glucose and fat. Mismatch between environmental conditions and the expression of metabolic hormones are likely to underlie variation in obesity and diabetes. Lifetime variation in endogenous reproductive hormones suggests a trade-off between early benefits for reproduction and later costs against survivorship expressed in population differences in the incidence of reproductive tumors, such as breast and prostate cancer.

Chapter 2 provides an overview of the neural and endocrine mechanisms that govern the timing and onset of puberty (reproductive maturation). The cells and hormones that comprise the hypothalamic–pituitary–gonadal (HPG) axis are introduced, followed by an explanation of how both negative and positive neuroendocrine feedback loops regulate circulating levels of gonadal steroid hormones in males and females. The rest of the chapter is devoted to mechanisms that govern the timing of puberty and activation of the HPG axis at the onset of puberty. The role of the metabolic hormone leptin as a permissive signal for the timing of puberty, the role of neural excitation and disinhibition in the awakening of the gonadotropin-releasing hormone (GnRH) neurons at the onset of puberty, and the role of the neuropeptide kisspeptin as a proximal driver of HPG axis activation are highlighted. Finally, recent research on hierarchical gene networks that are ultimately responsible for the developmental unfolding of activation of GnRH neurons at puberty onset is reviewed.

The endcoannabinoid system is an important regulator of appetite, food preference and body weight. It not only regulates metabolic feeding related hormones (leptin, ghrelin) in the brain and gut, but also regulates the brain reward circuitry involved in palatability based feeding. One of the primary roles of the endocannabinoid system is in the homeostatic regulation of feeding behaviour. New treatments for obesity are being developed that attempt to harvest the anti-obesity effects of the CB₁ antagonist, rimonabant, but that are devoid of the psychiatric side effects that became clearly known only after it was widely prescribed.

Multicellular organisms are endowed with coordinating systems that regulate and integrate the function of the different cells composing these organisms. Two main interacting systems perform this critical function: the nervous system and the endocrine system. The former employs electrochemical signals to convey regulatory inputs to peripheral organs and to receive information from them; the latter produces chemical agents that, in general, are transported systemically by the bloodstream to the target organs. The two systems are closely interconnected. The most conspicuous connection is that of the hypothalamus and the pituitary gland. Hypothalamic neurosecretory cells produce substances that are delivered to the portal blood vessels (see Chapter 5) and transported to the anterior pituitary (adenohypophysis), where they regulate the secretion of adenohypophyseal hormones. Other hypothalamic neurons send their axons to the posterior pituitary, from which they release their neurosecretory products directly into the bloodstream. The nervous system also innervates most, if not all, endocrine glands, including the gonads, the thyroid, and the adrenals. The nerves control not only blood flow but also the secretion of hormones. In turn, the endocrine system regulates the function of the nervous system. For example, gonadal and adrenocortical hormones act directly on the central nervous system to either inhibit or to stimulate the secretion of neuropeptides involved in the control of the pituitary-gonadal and pituitary-adrenal axes, respectively (i.e., gonadotrophin-releasing hormone [GnRH], also known as luteinizing hormone-releasing hormone [LHRH], and corticotropin-releasing hormone [CRH]; see Chapter 5). Although conventional definitions of the nervous and endocrine systems emphasize their differences, the two systems also display similarities. For instance, the nervous system produces not only substances that act across synapses, but it also releases signaling molecules that reach distant target cells via the bloodstream.

The hypothalamic-pituitary complex represents the core of the neuroendocrine system. The hypothalamus is composed of a diversity of neurosecretory cells arranged in groups, which secrete their products either into the portal blood system that connects the hypothalamus to the adenohypophysis (see later) or directly into the general circulation after storage in the neurohypophysis (see Chapter 6). Because of the nature of their actions, the hypothalamic hormones are classified as releasing or inhibiting hormones. The hypothalamic hormones delivered to the portal blood system are transported to the adenohypophysis, where they stimulate or inhibit the synthesis and secretion of different trophic hormones. In turn, these hormones regulate gonadal, thyroid, and adrenal function, in addition to lactation, bodily growth, and somatic development. No attempt will be made in this chapter to cover the actions of the different pituitary trophic hormones on their target glands, because they are discussed in detail in other chapters. An exception to this is growth hormone (GH). Although Chapter 11 considers several aspects of the control and actions of GH, a broader discussion of its physiological actions will be presented here because GH is the only anterior pituitary hormone that does not have a clear-cut target gland. The pituitary gland has two parts: the neurohypophysis, of neural origin (see Chapter 6), and the adenohypophysis, of ectodermal origin. In embryonic development, an evagination from the roof of the pharynx pushes dorsally to reach a ventrally directed evagination from the base of the diencephalon. The dorsally projecting evagination, known as Rathke’s pouch , forms the adenohypophysis, whereas the ventrally directed evagination of neural tissue forms the neurohypophysis. The neurohypophysis has three parts: the median eminence, the infundibular stem, and the neural lobe itself. The median eminence represents the intrahypothalamic portion and lies just ventral to the floor of the third ventricle protruding slightly in the midline. The main part of the neurohypophysis, the neural lobe, is connected to the median eminence by the infundibular stem.