Hormones: Diverse Structures for Diverse Functions:- Hormone Release Is Regulated by a Hierarchy of Neuronal and Hormonal Signals
The changing levels of specific hormones regulate specific cellular processes, but what regulates the level of each hormone? The brief answer is that the central nervous system receives input from many internal and ex ternal sensors—signals about danger, hunger, dietary intake, blood composition and pressure, for example—and orchestrates the production of appropriate hormonal signals by the endocrine tissues. For a more complete answer, we must look at the hormone-producing systems of the human body and some of their functional interrelationships. Figure 1 shows the anatomic location of the major endocrine glands in humans, and Figure 2 rep resents the “chain of command” in the hormonal signaling hierarchy. The hypothalamus, a small region of the brain (Fig. 3), is the coordination center of the endocrine system; it receives and integrates messages from the central nervous system. In response to these messages, the hypothalamus produces regulatory hormones (releasing factors) that pass directly to the nearby pituitary gland, through special blood vessels and neurons that connect the two glands (Fig. 3b). The pituitary gland has two functionally distinct parts. The posterior pituitary contains the axonal endings of many neurons that originate in the hypothalamus. These neurons produce the short peptide hormones oxytocin and vasopressin (Fig. 4), which then move down the axon to the nerve endings in the pituitary, where they are stored in secretory granules to await the signal for their release. The anterior pituitary responds to hypothalamic hormones carried in the blood, producing tropic hormones, or tropins (from the Greek tropos, “turn”). These relatively long polypeptides activate the next rank of endocrine glands (Fig. 2), which includes the adrenal cortex, thyroid gland, ovaries, and testes. These glands in turn secrete their specific hormones, which are carried in the bloodstream to the receptors of cells in the target tissues. For example, corticotropin-releasing hormone from the hypothalamus stimulates the anterior pituitary to release ACTH, which travels to the zona fasciculata of the adrenal cortex and triggers the release of cortisol. Cortisol, the ultimate hormone in this cascade, acts through its receptor in many types of target cells to alter their metabolism. In hepatocytes, one effect of cortisol is to increase the rate of gluconeogenesis. Hormonal cascades such as those responsible for the release of cortisol and epinephrine result in large amplifications of the initial signal and allow exquisite fine tuning of the output of the ultimate hormone (Fig. 5). At each level in the cascade, a small signal elicits a larger response. The initial electrical signal to the hypothalamus results in the release of a few nanograms of corticotropin-releasing hormone, which elicits the release of a few micrograms of corticotropin. Corticotropin acts on the adrenal cortex to cause the re lease of milligrams of cortisol, for an overall amplification of at least a millionfold. At each level of a hormonal cascade, feedback in hibition of earlier steps in the cascade is possible; an unnecessarily elevated level of the ultimate hormone or of one of the intermediate hormones inhibits the re lease of earlier hormones in the cascade. These feedback mechanisms accomplish the same end as those that limit the output of a biosynthetic pathway : a product is synthesized (or released) only until the necessary concentration is reached.
FIGURE 1 The major endocrine glands. The glands are shaded dark pink.
FIGURE 2 The major endocrine systems and their target tissues. Signals originating in the central nervous system (top) pass via a series of relays to the ultimate target tissues (bottom). In addition to the systems shown, the thymus, pineal gland, and groups of cells in the gastrointestinal tract also secrete hormones. Dashed lines represent neuronal connections.
FIGURE 3 Neuroendocrine origins of hormone signals. (a) Location of the hypothalamus and pituitary gland. (b) Details of the hypothalamus pituitary system. Signals from connecting neurons stimulate the hypothalamus to secrete releasing factors into a blood vessel that carries the hormones directly to a capillary network in the anterior pituitary. In response to each hypothalamic releasing factor, the anterior pituitary releases the appropriate hormone into the general circulation. Posterior pituitary hormones are synthesized in neurons arising in the hypothalamus, transported along axons to nerve endings in the posterior pituitary, and stored there until released into the blood in response to a neuronal signal.
FIGURE 4 Two hormones of the posterior pituitary gland. The carboxyl-terminal residues are glycinamide, ONHOCH2OCONH2 (as noted in Fig. 23–2, amidation of the carboxyl terminus is common in short peptide hormones). These two hormones, identical in all but two residues (shaded), have very different biological effects. Oxytocin acts on the smooth muscles of the uterus and mammary gland, causing uterine contractions during labor and promoting milk release during lactation. Vasopressin (also called antidiuretic hormone) increases water reabsorption in the kidney and promotes the constriction of blood vessels, thereby increasing blood pressure.
FIGURE 5 Cascade of hormone release following central nervous system input to the hypothalamus. In each endocrine tissue along the pathway, a stimulus from the level above is received, amplified, and transduced into the release of the next hormone in the cascade. The cascade is sensitive to regulation at several levels through feedback inhibition by the ultimate hormone. The product therefore regulates its own production, as in feedback inhibition of biosynthetic path ways within a single cell.
