Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Hormones
General Concept of Hormones

The Study of Hormones has evolved into an independent scientific discipline known as endocrinology. Modern endocrinology investigates the Chemical Structure of hormones produced by Endocrine glands, the relationship between hormonal Structure and function, the MOLECULAR MECHANISMS OF their action, and the physiology and Pathology of the Endocrine System*. Specialized research institutes and laboratories have been established, scientific journals are published, and international conferences, symposia, and congresses dedicated to endocrinology are regularly held. Today, endocrinology has emerged as one of the most rapidly expanding fields in biological science. It possesses its own Goals and Objectives, specific methodological approaches, and Research Methods. In our country, the Endocrinology Research Center of the Russian Academy of Medical Sciences serves as the leading scientific institution coordinating research in this field.

Hormones belong to a Class of BIOLOGICALLY ACTIVE SUBSTANCES that largely determine the state of physiological Functions in the intact Organism, the macro- and microstructures of Organs and Tissues, and The rate of biochemical processes. Thus, hormones are Organic compounds synthesized by specialized Cells of endocrine glands, secreted into the bloodstream, and exerting a regulatory influence on METABOLISM and physiological functions. This definition must be appropriately adjusted in light of the discovery of typical mammalian hormones in unicellular organisms (e.g., Insulin in microorganisms) or the potential synthesis of hormones by somatic cells in tissue culture (e.g., lymphocytes under the action of growth factors).

One of the remarkable features of living organisms is their ability to maintain the constancy of their internal environment—Homeostasis—through self-regulatory mechanisms, in which hormones play a pivotal role. In higher animals, the coordinated progression of all biological processes—not only within the organism as a whole, but also within the microenvironment of an individual Cell and even within specific subcellular structures (Mitochondria, microsomes)—is governed by neurohumoral mechanisms shaped by evolution. Through these mechanisms, the organism perceives diverse signals regarding Changes in the external and internal environments and finely regulates metabolic intensity. In regulating these processes and orchestrating a sequence of multiple reactions, hormones act as an intermediary link between The Nervous system and the action of Enzymes, which directly control metabolic rates. Currently, evidence has been obtained that hormones induce either a rapid (immediate) response by enhancing The activity of pre-existing enzymes present in tissues (characteristic of Peptide and Protein hormones) or, more typically for Steroid Hormones, a slow response associated with *de novo* enzyme synthesis. As will be shown later, steroid hormones influence the GENETIC APPARATUS OF The Cell, inducing the Synthesis of the corresponding mRNA, which, upon reaching the ribosome, serves as a template for the synthesis of a protein-enzyme molecule. It is hypothesized that Other Hormones (of protein nature) may also indirectly affect genes by phosphorylating non-histone Proteins, thereby controlling the rate of synthesis of corresponding enzymes. Consequently, any disruptions in hormone synthesis or degradation caused by various causal factors—including endocrine gland disorders (hypo- or hyperfunction states) or alterations in the structure and function of receptors and intracellular messengers—lead to impaired normal enzyme synthesis and, correspondingly, Metabolic Disorders.

* Recent studies provide compelling evidence that the endocrine system encompasses not only classic endocrine glands but also numerous other hormonal systems within the body's organs and tissues, which produce biologically active substances with hormone-like effects; these are regulated by the neuroendocrine system or act autonomously.

The origins of the science of endocrine glands and hormones date back to 1855, when T. Addison first described Addison's disease (bronze disease), associated with Adrenal gland damage and accompanied by specific Skin pigmentation. Claude Bernard introduced THE CONCEPT OF internal secretion glands, i.e., organs that release their secretions directly into the Blood. Later, Ch. Brown-Séquard demonstrated that the functional insufficiency of endocrine glands leads to The Development of diseases, whereas extracts derived from these glands exert a beneficial therapeutic effect. Today, there is irrefutable evidence that almost all Diseases of the endocrine glands (thyrotoxicosis, Diabetes Mellitus, etc.) develop As a result of impairments in the molecular mechanisms regulating metabolic processes, caused by insufficient or, conversely, excessive synthesis of the corresponding hormones in The Human Body.

The term "hormone" (from the Greek *hormao* — I excite or set in motion) was introduced in 1905 by W. Bayliss and E. Starling during their study of secretin, a hormone they discovered in 1902 that is produced in the duodenum and stimulates pancreatic juice secretion and Bile flow. To date, over a hundred different substances endowed with hormonal activity have been discovered, synthesized in endocrine glands, and involved in the Regulation of Metabolic processes. Specific features of the biological Action of Hormones have been established: a) hormones exhibit their biological effects at remarkably low concentrations (from 10^-6 to 10^-12 M); b) the hormonal effect is mediated through protein receptors and intracellular secondary messengers; c) although being neither enzymes nor Coenzymes, hormones nevertheless exert their action by increasing the rate of *de novo* enzyme synthesis or altering the Velocity of enzymatic catalysis; d) the action of hormones in the intact organism is determined to a certain extent by the controlling Influence of the Central Nervous System; e) the endocrine glands and the hormones they produce constitute a unified system closely interconnected through feedback mechanisms.

Under The Influence of various external and internal stimuli, impulses arise in specialized, highly sensitive receptors. These impulses are then transmitted to the central nervous system, and from there to the Hypothalamus, where the primary biologically active hormonal substances exerting a "distant" effect—the so-called releasing factors—are synthesized. A distinctive feature of releasing factors is that they do not enter the general bloodstream; instead, via the portal vessel system, they reach specific pituitary cells, where they stimulate (or inhibit) the Biosynthesis and release of pituitary trophic hormones. These trophic hormones are carried by the bloodstream to the target endocrine gland, promoting The production of the required hormone. This hormone subsequently acts on specialized organs and tissues (target organs), eliciting the corresponding chemical and physiological Responses of the whole organism.

Until recently, The final stage of this peculiar arc—the action of hormones on intracellular metabolism—remained the least understood. Evidence has now been obtained that this action is mediated through so-called Hormone Receptors, which are defined as chemical structures within corresponding target tissues containing highly specific sites (carbohydrate moieties of Glycoproteins and gangliosides) for hormone binding. The result of such binding is the initiation by receptors of specific biochemical reactions that ensure the realization of the target hormone's ultimate effect. Receptors for protein and Peptide Hormones are located on the outer surface of the cell (on The Plasma Membrane), whereas receptors for steroid hormones are situated in The Nucleus. A common characteristic of all receptors, regardless of their cellular localization, is the presence of strict spatial and structural complementarity between the receptor and its corresponding hormone.

The Molecular mechanisms of hormonal signal Transduction and The Role of secondary messengers in mediating the hormonal effect are detailed at the end of this chapter.