5.4The Endocrine System

The endocrine system refers to the system for transmitting information through hormones; the definition of “hormones” has undergone major changes over time.

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Adrenaline was the first hormone to be identified when Jokichi Takamine extracted it from the adrenal gland and crystallized it in 1901. However, the name “hormone” was first used by William Bayliss and Ernest Starling to describe secretin, which they discovered in 1902. A hormone is a substance secreted by an endocrine organ. It acts via the circulatory system on a target organ that has specific receptors, thereby modifying the functions of that organ. However, hormones secreted from the endocrine organs are not completely mature, and physiologically active substances (such as angiotensin) produced in the blood by enzymes can also be classified as hormones. Hormones are also produced in tissues and organs not traditionally considered to be part of the endocrine system, such as the heart, vascular endothelial cells, digestive tract, kidneys, and thymus glands. It has also been discovered over time that these hormones have functions that do not fit the definition of “endocrine,” such as “paracrine,” in which the secreted hormone form also acts on neighboring cells, and “autocrine,” in which it acts on the secreting cell itself (see Chapter 14).

In recent years, the progress in biochemical and molecular biological technology, in which trace amounts of proteins, RNA, and DNA are used to determine their sequences, and bioinformatics technology, which completes genomic information and extracts important information from it, it has been found that almost all tissues and organs produce various molecules that can be called hormones. Of the hormone-producing tissues, neurosecretion in particular refers to the phenomenon of a hormone being produced and secreted by neurological tissues. Neurosecretion is a phenomenon that links the neurological system with the endocrine system. In light of the expanding definition of hormones, the action of the neurological system to transmit information using catecholamine and acetylcholine through synapses can also be considered as a paracrine function of hormones (see Chapter 14, Fig. 14-1). Moreover, cytokines that are produced by swarm cells such as hemocytes and lymphocytes and that participate in immunity and inflammation have been difficult to differentiate from hormones (see Chapter 21).

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The Diversity of Hormones and Receptors

The molecular variety of hormones is constantly expanding with the discovery of new hormones. Hormone molecules can be classified into comparatively low-molecular-weight peptides (insulin, vasopressin, etc.), high-molecular-weight proteins (gonadotropin), steroids (estrogen and cortisol), amino acid derivatives (adrenaline, melatonin, etc.), arachidonic acid derivatives (prostaglandin), etc. (see Chapter 14, Table 14-1). Furthermore, polysaccharide chains, fatty acids, or phosphoric acid are necessary for the functioning of some polypeptide and protein hormones. If hormones are classified as per time of action, then they could be described as being fast-acting short-term hormones that are secreted rapidly and that immediately disappear from blood circulation (having a half-life in units of seconds to minutes) and slow-acting long-term hormones that are secreted slowly and remain in the blood stream for a long time (having a half-life in units of hours to days); the former include low-molecular-weight hormones such as oligopeptides and amino acid derivatives, while the latter include protein and steroid hormones.

The effects of peptide and protein hormones appear when they bind to specific cell membrane receptors. Many different types of membrane receptors have been identified, such as those that couple with various G proteins and those that are independent molecules and variously have kinase activity or guanylate cyclase activity within the cell. In addition, hormones transmit information through various secondary messengers to finally regulate cell functions by phosphorylating or dephosphorylating a target protein through different kinases and phosphatases (Refer to Chapter 14 for more information). The number of different types of G protein-coupled receptors is particularly high. They all have seven transmembrane regions within a molecule. To connect a hydrophobic amino acid to a transmembrane region, the candidate protein for the receptor is identified by its structural characteristics. Determining the human genome based on these characteristics has led to the discovery of many orphan receptors for which no ligand (the molecule that binds to the receptor) has ever been found. There has been a boom in research to discover new ligand hormones based on these orphan receptors. This approach is called reverse pharmacology because it is the reverse of prior approaches (determination of receptors from their ligands). On the other hand, highly lipophilic thyroid hormones and steroid hormones bind to receptors found in the cytoplasm by penetrating the cell membrane. These receptors migrate to the nucleus once they have bound to the hormone, i.e., their ligand, and regulate expression of a specific gene. Accordingly, hormones that have nuclear receptors are often slow-acting, long-term hormones. Similar to hormones, the concept of receptors has also been expanding recently, and peptide and steroid hormone receptors found within the cell and cell membrane, respectively, have been reported. In addition to hormone-binding proteins found in the blood, which bind to hormones in order to regulate their effects, receptor-regulating proteins found in the cell membrane or cytoplasm, which regulate the activity of a receptor by binding to it, control the activities of hormones.

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