Mechanism of Hormone Action dr. Dian Hasanah Laboratorium Fisiologi Fakultas Kedokteran Universitas Brawijaya
Chemical Messenger The multiple activities of the cells, tissues, and organs of the body are coordinated by the interplay of several types of chemical messenger systems. Several types of chemical messenger systems: a. Neurotransmitters are released by axon terminals of neurons into the synaptic junctions and act locally to control nerve cell functions. Example: acetylcholine. b. Endocrine hormones are released by glands or specialized cells into the circulating blood and inﬂuence the function of cells at another location in the body.
Chemical Messengerc. Neuroendocrine hormones are secreted by neurons into the circulating blood and inﬂuence the function of cells at another location in the body. Examples: oxytocin, vasopressin.d. Paracrines are secreted by cells into the extracellular ﬂuid and affect neighboring cells of a different type. Example: somatostatin secreted by delta cells in the pancreas.e. Autocrines are secreted by cells into the extracellular ﬂuid and affect the function of the same cells that produced them by binding to cell surface receptors. Examples: somatomedin, some growth factors.f. Cytokines are peptides secreted by cells into the extracellular ﬂuid and can function as autocrines, paracrines, or endocrine hormones. Example: interleukins.
Body’s Two Major Regulatory Systems The endocrine system is one of the body‟s two major regulatory systems. The other one is the nervous system. In general, nervous system coordinates rapid, precise responses and is especially important in mediating the body‟s interaction with the external environment. The endocrine, by contrast, primarily controls activities that require duration rather than speed. It regulates, coordinates, and integrates cellular and organ function at distance.
The Functions of Endocrine System1. Regulating organic metabolism and H2O and electrolyte balance, which are important collectively in mantaining a constant internal environment.2. Inducing adaptive changes to help the body cope with stressful situations.3. Promoting smooth, sequential growth and development.4. Controlling reproduction.5. Regulating red blood cell production.6. Along with the autonomic nervous system, controlling and integrating activities of both the circulatory and digestive systems.
Complexity of the Endocrine Systema. A single endocrine gland may produce multiple hormones. Example: anterior pituitary secretes 6 different hormones (GH, FSH, LH, prolactin, TSH, ACTH).b. A single hormone maybe secreted by more than one endocrine gland. Example: somatostatin is secreted by hypothalamus and pancreas.c. Frequently, a single hormone has more than one type of target cell and therefore can induce more than one type of effect, typically by binding with different subtypes of receptors. Example: vasopressin binds V1a and V2 receptors.d. The rate of secretion of some hormones varies considerably over the course of time in a cyclic pattern. Therefore, endocrine systems also provide temporal (time) coordination of function. This is particularly apparent in endocrine control of reproductive cycle. Examples: estrogen, progesterone.
Complexity of the Endocrine Systeme. A single target cell may be influenced by more than one hormone. Some cells contain an array of receptors for responding in different ways to different hormones. Example: liver cells are influenced by insulin and glucagon.f. The same chemical messenger may be either a hormone or a neurotransmitter, depending on its source and mode of delivery to the target cell. Example: norepinephrine.g. Some organs are exclusively endocrine in function (they specialize in hormone secretion alone), example: anterior pituitary. Whereas others also perform nonendocrine functions, examples: testes secrete testosterone and also produce sperm.
Definition of Hormone Hormone is a blood-borne chemical messenger synthesized and released by endocrine gland that act on target cells located a long distance from the location it released. Tropic (means “nourishing”) hormone is a hormone that its primary function is to regulate hormone secretion by another endocrine gland and to maintain their endocrine target tissues.
Classes of HormonesClasses of hormones based on chemical structure:a. Proteins and polypeptides, including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.b. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).c. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine).There are no known polysaccharides or nucleic acid hormones.
Classes of HormonesClasses of hormones based on their solubility in wateror lipid:a. Water-soluble hormones (hydrophilic): peptides and catecholamines.b. Lipid-soluble hormones (lipophilic): steroid and thyroid hormones.
Hormone ReceptorsThe locations for the different types of hormone receptorsare generally the following:a. In or on the surface of the cell membrane. The membrane receptors are speciﬁc mostly for the protein, peptide, and catecholamine hormones.b. In the cell cytoplasm. The primary receptors for the different steroid hormones are found mainly in the cytoplasm.c. In the cell nucleus. The receptors for the thyroid hormones are found in the nucleus and are believed to be located in direct association with one or more of the chromosomes.
Plasma ConcentrationPlasma concentration of a hormone is influenced by:a. Hormone secretion.b. Peripheral hormone conversion. Example: T4 T3 (more active).c. Hormone transport (bound or unbound to plasma protein).d. Hormone inactivation. Peptide hormones are inactivated by hydrolysis of peptide bonds; or engulfed and degradaded intracellularly. Catecholamines are enzymatically converted into inactive forms. Lipophilic hormones are inactivated by alteration of the active portions, and liver adds charged groups to make them water soluble.a. Hormone excretion by liver and kidneys.
Hormone ClearanceHormones are “cleared” from the plasma in severalways, including:a. Binding with the tissues.b. Metabolic destruction by the tissues.c. Excretion by the liver into the bile.d. Excretion by the kidneys into the urine.
Negative Feedback After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone tend to suppress its further release. In other words, the hormone (or one of its products) has a negative feedback effect to prevent oversecretion of the hormone or overactivity at the target tissue.
Positive Feedback In a few instances, positive feedback occurs when the biological action of the hormone causes additional secretion of the hormone. One example of this is 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 then acts on the ovaries to stimulate additional secretion of estrogen, which in turn causes more secretion of LH.
Neuroendocrine Reflexes Many endocrine control systems involve neuroendocrine reflexes, which include neural as well as hormonal components. The purpose of such reflexes is to produce a sudden increase in hormone secretion in response to a specific stimulus, frequently a stimulus external to the body. For example is the increased secretion of cortisol, the „”stress hormone”, by the adrenal cortex during a stress response.
Down Regulation When the plasma concentration of hormone is chronically elevated, the total number of target-cell receptor for hormone is gradually reduced as a direct result of the effect a sustained elevation of hormone has on the hormone receptors. This phenomenon prevents the target cells from overreacting to a prolonged high concentration of hormone.
Down RegulationThis down-regulation of the receptors can occur as a result of:1. Inactivation of some of the receptor molecule.2. Inactivation of some of the intracellular protein signaling molecules.3. Temporary sequestration of the receptor to the inside of the cell, away from the site of action of hormones that interact with cell membrane receptors.4. Destruction of the receptors by lysosomes after they are internalized.5. Decreased production of the receptors.In each case, receptor down-regulation decreases the targettissue‟s responsiveness to the hormone.
Endocrine Disorders Too Little Hormone Activity Too Much Hormone ActivityToo little hormone secreted by Too much hormone secreted bythe endocrine gland the endocrine gland(hyposecretion)* (hypersecretion)*Increased removal of the hormone Reduced plasma protein bindingfrom the blood of the hormone (too much free,Abnormal tissue responsiveness to biologically active hormone)the hormone Decreased removal of the Lack of target-cells receptors hormone from the blood Lack of an enzyme essential to Decreased inactivation the target-cell response Decreased excretion *Most common causes of endocrine dysfunction
Permissiveness With permissiveness, one hormone must be present in adequate amounts for the full exertion of another hormone‟s effect. In essence, the first hormone, by enhancing a target cell‟s responsiveness to another hormone, “permits” this other hormone to exert its full effect. Example: thyroid hormones increases the number of receptors for epinephrine.
Synergism Synergism occurs when the actions of several hormones are complementary and their combined effect is greater than the sum of their separate effects. Example: FSH and testosterone are required for maintaining the normal rate of sperm production.
Antagonism Antagonism occurs when one hormone causes the loss of another hormone‟s receptors, reducing the effectiveness of the second hormone. Example: progesterone inhibits uterine responsiveness to estrogen during pregnancy, by causing loss of estrogen receptors.