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I. EVOLUTION: When evolving from a single cell to multicellular, the organism must be able to carry out homeostasis [homeostasis], reproduction, and appropriate responses to environmental stress.
II. INITIAL REMARKS: Endocrinology is a subdiscipline within the field of physiology. Physiology is the study of normal biological functions. Thus, endocrinology is the study of normal endocrine functions. Endocrinology and molecular endocrinology are rapidly expanding fields.
III. DEFINING THE ENDOCRINE SYSTEM AND HORMONES
Classically, the endocrine system consists of the endocrine glands (e.g., the thyroid, adrenals, gonads, pituitary, pancreas, etc.) Classically, it consisted of specialized tissues whose products were (are) secreted into the interstitial compartment and absorbed by blood. Classically, these unique chemical products were called hormones. Classically, a hormone was defined as a molecule produced by living cells and carried by the blood circulation to other parts of the organism where it produced specific effect(s). However, as the preface of your textbook states: "It is now amply documented that hormones may originate from either endocrine or neural tissue…..Hormones are produced in many sites throughout the body and may be released either directly into the blood, into neuronal synapses, or into the immediate intercellular space to affect adjacent cellular activity. NOTE: Click here for a nice layman’s overview of hormones and endocrinology .
Thus, hormones are organic molecules that relay information. But, the nervous system also relays information as its principal function. We now know that the ENDOCRINE SYSTEM and the NERVOUS SYSTEM are sometimes indistinguishable from one another. However, there are certain obvious differences between these two systems of communication:
1. The transmission of nervous information is much faster.than the usually slow movement of hormones (and the slow response time of hormonal target tissues).
2. The transmission of nervous information is via distinct tracts of neurons, whereas transmission of hormonal information is via extracellular fluids and the circulatory system.
3. The transmission of nervous information occurs at both the conscious and the subconscious levels, whereas hormonal information is subconscious, only.
4. The transmission of nervous information appraises the body of conditions of both the internal and the external environments, whereas hormonal information is conveyed by non-neuronal signals between cells and tissues within the internal environment, only.
NOTE: Although endocrine secretory cells may be cuboidal, and neurons are usually very long, both types of cells (like all living cells) have membrane potentials, and they usually undergo depolarization during the secretion of their hormones or neurohormones.
V. ENDOCRINOLOGY IN HISTORICAL PERSPECTIVE
1. de Graaf and Malpighi, in 1666, analyzed anatomical structures including "female testes".
2. Berthold, in 1849, published the first evidence that castrated cockerels failed to develop their combs and wattles--as well as failing to exhibit male behavior. Replacement of the testes restored these sex-related characteristics (Fig. 1.1).
3. Bayliss and Starling, in 1902, first demonstrated that a substance (i.e., secretin) produced by the mucosa of the small intestines stimulated (via blood) the pancreas to secrete digestive juices. (NOTE: Starling, in 1905, introduced the term "hormone", which is Greek for "I arouse to activity, or I excite".)
4. Loewi, in 1921, demonstrated that the vagus nerve releases substances that affect the relaxation (by acetylcholine) and contraction (by norepinephrine) of cardiac muscle.
5. Banting and McLeod, in 1922, found that the islets of Langerhans were responsible for carbohydrate metabolism and the prevention of diabetes.
6. Sanger, in 1953, established the amino acid sequence for the protein hormone "insulin".
7. Du Vigneaud, in 1953, was the first to synthesize peptide hormones, namely oxytocin and vasopressin.
8. Sutherland, in 1962, discovered adenylate cyclase and cyclic AMP.
9. Guillemin and Schally, in 1970's, isolated and determined the structures of hypothalamic releasing factors (i.e., regulatory peptides).
10. Yalow, in 1970's, developed the radioimmunoassay method for detecting minute amounts of peptides, proteins and steroids, etc.
11. Samuelsson and Vane, in 1982, discovered the importance of prostaglandins and the metabolism of other eicosanoids.
12. Levi-Montalcini and Cohen, in 1986, were honored for discovering NGF and EGF and the importance of these growth factors in cell growth and development.
13. Fischer and Krebs, in 1992, won the Nobel Prize for their discoveries concerning reversible protein phosphorylation as a biological regulatory mechanism.
14. Gilman and Rodbell, in 1994, won the Nobel Prize for their discovery of G-proteins and the role of these proteins in signal transduction in cells.
15. Carlsson, Greengard, and Kandel, in 2000, won the Nobel Prize for their discoveries concerning signal transduction in the nervous system.
VI. THE BASIC TYPES OF HORMONES (proteins vs steroids)
1. Amines are derivatives of the amino acid tyrosine, e.g., epinephrine, norepinephrine, dopamine, etc. (Note the exception of thyroxine and T3).
2. Peptides/proteins are as small as only 3 amino acids (e.g., thyrotropin-releasing hormone) to larger peptides (e.g., secretin, gastrin, parathyroid hormones, calcitonin, oxytocin, and vasopressin) to still larger peptides and proteins (e.g., insulin, glucagon, somatostatin, growth hormone, prolactin, and adrenocorticotropin (ACTH)).
3. Glycoproteins are proteins with one or more carbohydrate units attached to the molecule (e.g., thyrotropin, FSH, LH, and hCG, with the alpha subunits common in the last three).
B. HORMONES TARGETED TOWARD NUCLEAR RECEPTORS (or to the cytoplasm)
1. Steroids are lipid soluble hormones such as cortisol, aldosterone, testosterone, estrogen and progesterone. (They have important functions in regulating carbohydrate metabolism, salt balance, and reproductive processes.)
WHY HORMONES? Why are all these chemical messengers necessary? Re-emphasize that biology teaches us that living systems evolved from simple to multicellular forms. As different types of cells took on specialized functions, they had to be able to communicate with one another. HORMONES ARE THE CHEMICAL MESSENGERS OF MULTICELLULAR ORGANISMS. We now realize hormones are not products only of endocrine glands, but of all cells. We have come to realize that every multicellular organism has what Claude Bernard called "le milieu interieur", i.e., the internal environment. This internal environment must be maintained in a relatively constant, or steady, state. The physiological process of maintaining this internal environment (in spite of a constantly changing external environment) is called HOMEOSTASIS. The idea of homeostasis was conceived in 1939 by an eminent physiologist at Harvard Medical School named Walter Cannon. Examples of homeostasis include maintenance of a constant blood-glucose level (Fig. 1.6) and maintenance of a constant blood-calcium level (Fig. 1.7). Homeostasis is, collectively, the various processes within the body which function to maintain metabolic consistency, mainly through negative-feedback mechanisms. THE ENDOCRINE SYSTEM HAS, AS ITS PRINCIPAL FUNCTION, HOMEOSTASIS.
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