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Human Physiology Course Human Physiology Course Endocrine System Principles of hormonal regulation Assoc. Prof. Mária Pallayová, MD, PhD [email protected] Department of Human Physiology, PJ Safarik University FOM April 6-7, 2020 (9th week – Summer Semester 2019/2020) Chemical messenger systems Types of chemical messenger systems: Neurotransmitters Endocrine hormones Neuroendocrine hormones Paracrines Autocrines Cytokines Neurotransmitters are released by axon terminals of neurons into the synaptic junctions act locally to control nerve cell functions. Endocrine hormones are released by glands or specialized cells into the circulating blood influence the function of target cells at another location in the body. Neuroendocrine hormones are secreted by neurons into the circulating blood influence the function of target cells at another location in the body. Paracrines are secreted by cells into the extracellular fluid affect neighboring target cells of a different type. Autocrines are secreted by cells into the extracellular fluid affect the function of the same cells that produced them. Cytokines are peptides secreted by cells into the extracelular fluid can function as autocrines, paracrines, or endocrine hormones. e.g., the interleukins and other lymphokines secreted by helper cells and act on other cells of the immune system. adipokines= cytokine hormones (e.g., leptin) produced by adipocytes. Hormonal vs. Humoral ????? Hormonal vs. Humoral hormonal = endocrine humoral = endocrine + autocrine + paracrine The Endocrine Sytem the endocrine signaling communication and coordination system. relies on hormones, chemical substances that are released into the bloodstream, to deliver messages to cells of the body. Hormones and Functions Hormones are produced by: – endocrine glands – endocrine tissues (the brain, heart, kidney, adipose tissue, and GI tract). Endocrine cells may be: – diffusely located, e.g. in the stomach and intestines – found in clusters, e.g., the neurons of the hypothalamus. Endocrine Glands Endocrine glands = ductless glands that empty their hormonal products directly into the blood. Anatomical loci of the principal endocrine glands and tissues of the body Guyton and Hall Question What is the largest endocrine tissue? Hormones signaling molecules involved in regulating a variety of processes. The word “hormone” is derived from the Greek hormaein, which means to “excite” or to “stir up.” Function: to regulate, integrate, and coordinate a variety of different physiological processes. Hormones Regulate and Coordinate Many Functions The processes that hormones regulate fall into areas: 1) the digestion, utilization, and storage of nutrients; 2) growth and development; 3) ion and water balance; 4) reproductive function. Hormones and Functions Thyroid hormone Parathyroids Thymus Adrenal glands Endocrine pancreas Ovaries, Testes Pineal Pituitary Hypothalamus-Pituitary Axis GIT, adipose tissue, brain, heart, kidney, ... Guyton and Hall Essentials of Human Physiology Hormone receptors determine whether a cell will respond to a hormone are the molecular entities (usually a protein or glycoprotein) either outside or within a cell that recognize and bind a particular hormone. Only target cells that possess specific receptors for the hormone, will respond to that hormone. When a hormone binds to its receptor, biological effects characteristic of that hormone are initiated. the basis for specificity in cell-to-cell communication rests at the level of the receptor Feedback regulation an important part of endocrine function usually negative feedback a few positive feedback mechanisms simple first-order feedback loops more complex multilevel second- or third-order feedback loops Simple Feedback Loops First-order feedback regulation is the simplest type and forms the basis for more complex modes of regulation. E.g., an endocrine cell secretes a hormone that produces a specific biological effect in its target tissue. It also senses the magnitude of the effect produced by the hormone. As the biological response increases, the amount of hormone secreted by the endocrine cell is appropriately decreased. Negative feedback loop Negative Feedback Prevents Overactivity of Hormone Systems. After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone tend to suppress its further release. E.g.: ft4 - TSH Feedback regulation of hormones can occur at all levels, including gene transcription and translation steps involved in the synthesis of hormones and steps involved in processing hormones or releasing stored hormones. Negative feedback loop The controlled variable is sometimes not the secretory rate of the hormone itself but the degree of activity of the target tissue. only when the target tissue activity rises to an appropriate level will feedback signals to the endocrine gland become powerful enough to slow further secretion of the hormone. Positive feedback loop the surge of luteinizing hormone (LH) that occurs as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation the secreted LH acts on the ovaries to stimulate additional secretion of estrogen, which in turn causes more secretion of LH eventually, LH reaches an appropriate concentration and typical negative feedback control of hormone secretion is then exerted Complex Feedback Loops More commonly, feedback regulation in the endocrine system is complex, involving second- or third-order feedback loops. E.g., multiple levels of feedback regulation may be involved in regulating hormone production by various endocrine glands under the control of the anterior pituitary. A complex, multilevel feedback loop The hypothalamic-pituitary- target gland axis Solid lines indicate stimulatory effects; dashed lines indicate inhibitory, negative- feedback effects. Lippincott Signal Amplification is an important characteristic of the endocrine system Blood concentrations of hormones are exceedingly low, generally, 10-9 to 10-12 mol/L. Therefore, for hormones to be effective regulators of biological processes, amplification must be part of the overall mechanism of hormone action. Signal Amplification Amplification generally results from the activation of a series of enzymatic steps involved in hormone action. At each step, many times more signal molecules are generated than were present at the prior step, leading to a cascade of increasing numbers of signal molecules. The self-multiplying nature of the hormone action pathways provides the molecular basis for amplification in the endocrine system. Chemical structure of hormones Amino Acid-Derived Hormones - the simplest hormones in terms of structure, consist of one or two modified amino acids Protein and Polypeptide Hormones Steroid Hormones - derived from cholesterol Eicosanoids - lipids synthesized from FA chains of phospholipids found in plasma membrane („local hormones“) Amino acid-derived hormones derived from one or two amino acids are small in size and often hydrophilic are formed by conversion from a commonly occurring amino acid (epinephrine and thyroxine are derived from tyrosine) the synthesis of amino acid-derived hormones can be influenced by a variety of environmental/pharmacological agents Polypeptide Hormones are quite diverse in size and complexity may be as small as the tripeptide thyrotropin-releasing hormone (TRH) or as large as human chorionic gonadotropin (hCG), which is a glycoprotein composed of separate alpha and beta subunits Polypeptide and Protein Hormones Are Stored in Secretory Vesicles Until Needed. a number of families of hormones can be grouped into families based on homology with regard to amino acid sequence and structure Examples of Peptide Hormone Families Glycoprotein Family Secretin Family . Luteinizing hormone (LH) . Secretin . Follicle-stimulating hormone (FSH) . Vasoactive intestinal peptide (VIP) . Thyroid-stimulating hormone (TSH) . Glucagon . Human chorionic gonadotropin (hCG) . Gastric inhibitory peptide (GIP) Growth Hormone Family Insulin Family . Growth hormone (GH) . Insulin . Insulin-like growth factor I . Prolactin (PRL) . Insulin-like growth factor II . Human placental lactogen (hPL) . Relaxin Steroid Hormones lipid-soluble, hydrophobic molecules usually synthesized from cholesterol and are not stored. large stores of cholesterol esters in cytoplasm vacuoles can be rapidly mobilized for steroid synthesis after a stimulus. Much of the cholesterol in steroid-producing cells comes from the plasma, but there is also de novo synthesis of cholesterol in steroid- producing cells. Because the steroids are highly lipid soluble, once they are synthesized, they simply diffuse across the cell membrane and enter the interstitial fluid and then the blood. Steroid Hormones They can be classified into six categories, based on their primary biological activity. 1) Cortisol (a glucocorticoid) 2) Aldosterone (a mineralocorticoid) 3) Testosterone (an androgen) 4) Estradiol (an estrogen) 5) Progesterone (a progestin) 6) 1,25 (OH)2 Cholecalciferol (a calciferol) 1) Glucocorticoids Glucocorticoids (e.g., cortisol) are primarily produced in cells of the adrenal cortex. Glucocorticoids regulate processes involved in glucose, protein, and lipid homeostasis. Glucocorticoids generally produce effects that are catabolic in nature. 2) Mineralocorticoids Mineralocorticoids (e.g., aldosterone) are produced in cells of the outermost portion of the adrenal cortex. Aldosterone is primarily involved in regulating Na and K balance by the kidneys and is the principal
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