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Hormones: An overview Paper: Zoology Lesson: Hormones: An overview Author: Dr. Smita Bhatia College/Department: Ramjas College, University of Delhi Institute of Life Long Learning, University of Delhi 0 Hormones: An overview Table of Contents Introduction Type of hormones Lipid soluble hormones Steroid hormones Thyroid hormones Nitric oxide Water Soluble hormones Peptides and proteins Biogenic amines Eicosanoids Mode of action of hormones Action of Lipid-soluble hormones Action of Water-soluble hormones Regulation of Hormone secretion Hormone interactions Summary Exercises Glossary References Institute of Life Long Learning, University of Delhi 1 Hormones: An overview Introduction All functions of the body are very finely regulated to achieve a state of homeostasis. The major regulatory systems of the body are the endocrine system and the nervous system (and the interface between the two; the neuroendocrine mechanisms – where secretions of the neurons act directly as hormones e.g. oxytocin and vasopressin or cause secretion of another hormone e.g., stimulation of the sympathetic nervous system causes the release of hormones from the adrenal medulla). The endocrine system consists of glands that release their secretions (hormones) directly into the blood stream as they do not have any ducts to convey their secretions to the target organs (or cells). Endocrine glands are, therefore, called ‘Ductless Glands’ (Fig. 1). Also, the target organ may be at a distant location or there may be multiple target organs for a hormone where it may not be possible to reach through ducts. Fig.1. Release and action of hormones Value addition: Did you Know Heading text: Types of secretion Source: ILLL in house Institute of Life Long Learning, University of Delhi 2 Hormones: An overview While hormones (are released directly into the bloodstream (or in the interstitial fluid from where they diffuse into the blood) and act on target cells located at a distance, some secretions of the cells act on the target cells in the close vicinity. These secretions are called Paracrine agents. Some cells produce secretions that regulate the activities of the same cell. These secretions are known as Autocrine agents. Paracrine and autocrine agents are local hormones. Source: Author, ILLL in house Table 1. Differences between the endocrine and nervous system NERVOUS SYSTEM ENDOCRINE SYSTEM Institute of Life Long Learning, University of Delhi 3 Hormones: An overview Neurotransmitters are released from neurons Hormones are released from endocrine (ductless) glands Neurotransmitters act locally Neurotransmitters act on glands, Hormones act on distant target organs or cells Hormones act on a variety of cells muscle cells or other neurons Action of neurotransmitters is very fast Action of hormones may be fast or slow Effect of neurotransmitters lasts for a short Effect of hormones may last a few time seconds, hours or several days The various homeostatic functions of hormones include regulation of: metabolism and energy balance contractile activities of smooth and cardiac muscle secretory activities of glands growth and development functioning of the reproductive system establishment of circadian rhythms chemical composition of various body fluids some immune system activities Institute of Life Long Learning, University of Delhi 4 Hormones: An overview Fig.2. Location of endocrine glands in the body Source: http://bio1152.nicerweb.com/Locked/media/ch45/45_06HumanEndocGlands.jpg Free for educational purpose Types of Hormones Depending on their solubility, hormones can be categorized into two groups: 1. LIPID-SOLUBLE HORMONES Steroid Hormones These are derived from cholesterol e.g. male and female sex hormones and hormones of the adrenal cortex. a. Synthesis They are synthesized from cholesterol (see Figure 3) which is usually picked up from the plasma or may be synthesized de novo. Steroids are not stored in their ready form but are derived from cholesterol esters stored in cytoplasmic vacuoles. Institute of Life Long Learning, University of Delhi 5 Hormones: An overview Fig.3. Synthesis of different steroids from cholesterol Source: http://en.wikipedia.org/wiki/Steroid_hormone#mediaviewer/File:Steroidogenesis.svg Häggström M, Richfield D (2014). "Diagram of the pathways of human steroidogenesis". Wikiversity Journal of Medicine 1 (1). DOI:10.15347/wjm/2014.005. ISSN 20018762. Institute of Life Long Learning, University of Delhi 6 Hormones: An overview b. Transport Since steroid hormones are not water-soluble, they are not transported in dissolved form in the plasma. Specific transport proteins in the plasma carry specific steroids e.g. corticosteroid-binding-globulin (CBG, also known as transcortin) that transports 9095% of cortisol. The rest 5-10% of the hormone remains free in the plasma and is available for binding to the receptors in the target cells. Equilibrium exists between the bound and the free hormone. As the free hormone is lost from circulation, more hormones are released from the plasma proteins. Since lipid-soluble hormones are bound to plasma proteins they are removed from the blood (by degradation in the liver and excretion by the kidneys) at a lower rate and therefore, they have a longer half-life (half-life of a substance is the time taken for the concentration of that substance to reduce to half of its original concentration). Thyroid Hormones a. Synthesis Hormones of the thyroid gland, Tri-iodothyronine (T3) and thyroxine (tetra- iodothyronine; T4) are derived from the amino acid tyrosine by coupling of iodinated tyrosine molecules. The phenolic rings of tyrosine and addition of iodine makes these hormones lipid-soluble (Figure 4). These hormones are stored in the follicles of the thyroid gland bound to the protein thyroglobulin. Upon stimulation, they are released by proteolysis of thyroglobulin. I OH I CH I O I I NH2 TYROSINE HOOC CH I I NH2 HOOC OH I I CH I O O CH2 CH2 CH2 CH2 HOOC OH OH NH2 HOOC CH NH2 TRIIDOTHYRONINE (T3) “REVERSE T3” (INACTIVE) Institute of Life Long Learning, University of Delhi 7 THYROXINE (T4) Hormones: An overview Fig. 4. Structure of the thyroid hormones Source: Author, ILLL in House b. Transport Since thyroid hormones are also water-insoluble (lipid-soluble), they are transported in the plasma bound to the transport protein, thyroxine-binding globulin (TBG). Value addition: Did you Know Transport proteins for lipid-soluble hormones not only serve to carry these hormones in the plasma but also: • Provide a ready stock of hormones • Increase the half-life of these hormones as they are not as readily filtered by the kidneys Source: Author Nitric Oxide (NO) This is a gas, which acts as a hormone as well as a neurotransmitter. a. Synthesis It is not formed in advance but synthesized when needed. It is formed from the amino acid arginine by the activity of enzyme Nitric Oxide Synthase (NOS). b. Transport Nitric oxide, known to act only locally till recently, has been found to be transported in blood by hemoglobin and other proteins. Since it is lipid-soluble it easily diffuses into the target cells. It lasts for about 6 seconds after which it reacts with water and oxygen to form inactive nitrites and nitrates. Value addition: Did you Know NO was first discovered as a substance produced by endothelial cells of the blood vessels where it acts as a vasodilator. It was then named as the Endothelium Derived Relaxation Factor (EDRF). Source: Author 2. WATER-SOLUBLE HORMONES Institute of Life Long Learning, University of Delhi 8 Hormones: An overview Peptides and proteins These consist of amino acids joined together by peptide bonds. The number of amino acids may vary from 3 to 200. Those containing less than 100 amino acids are called peptides e.g., oxytocin and vasopressin (each containing 9 amino acids) and those with more than 100 amino acids are called proteins e.g., growth hormone containing 191 amino acids. a. Synthesis They are synthesized by the rough endoplasmic reticulum as inactive preprohormones. They undergo several modifications at different steps to finally give rise to the active hormone (Figure 5). Ca2+ Fig. 5. Synthesis and secretion of protein and peptide hormones Institute of Life Long Learning, University of Delhi 9 Hormones: An overview Source: Author, ILLL in house The following steps show the formation and secretion of an active hormone: Preprohormones (inactive) synthesized by the rough endoplasmic reticulum A part of this molecule is cleaved by the endoplasmic reticulum Prohormones (inactive) Enzymes in the Golgi apparatus cleave this into a smaller, active hormone Active Hormones Packaged into secretory vesicles by the Golgi apparatus Secretory vesicles containing active hormone stored in the cytoplasm, some bound to the cell membrane Appropriate stimulus The secretory vesicles release their contents in the form of granules into the interstitial fluid or the blood stream by exocytosis. Institute of Life Long Learning, University of Delhi 10 Hormones: An overview Source: Author, ILLL in house Biogenic Amines a. Synthesis These are the hormones derived from amino acids tyrosine and tryptophan. They retain an amino group, hence called amines. Those derived from tyrosine are called catecholamines (Figure 6) and include epinephrine, norepinephrine (both from adrenal medulla) and dopamine (recall here that thyroid hormones are also derived from tyrosine but they are not water-soluble because they do not retain the amino group but contain two phenolic rings and iodine that makes them lipid-soluble- Figure 4). Serotonin and melatonin are derived from the amino acid tryptophan. Biogenic amines also act as neurotransmitters. Institute of Life Long Learning, University of Delhi 11 Hormones: An overview O OH HO TYROSINE NH2 tyrosine-3-monoxygenase Tetrahydrobiopterin O HO L-DOPA OH NH2 HO aromatic L-amino acid decarboxylase Pyridoxal phosphate HO HO NH2 DOPAMINE dopamine beta-hydroxylase Ascorbate OH HO HO NH2 NOREPINEPHRINE phenylethanolamine-N-methyltransferase S-adenosylmethionine OH HO NHCH3 EPINEPHRINE HO Fig. 6. Synthesis of Catecholamines from Tyrosine Source: Author, ILLL in hous Institute of Life Long Learning, University of Delhi 12 Hormones: An overview Eicosanoids a. Synthesis These hormones are derived from a 20-carbon fatty acid, arachidonic acid (‘Eicos’ meaning twenty). These include prostaglandins, thrombokines and leukotrienes (Figure 7). All water-soluble hormones are carried dissolved in plasma without any transport proteins. LEUKOTRIENES LINEAR PATHWAY DIACYLGLYCEROL Lipoxygenase ARACHIDONATE PGH2 Synthase CYCLIC PATHWAY Prostacyclin Synthase PHOSPHOLIPIDS PROSTAGLANDIN H2 Thromboxane Synthase THROMBOXANES PROSTACYCLINS OTHER PROSTAGLANDINS Fig. 7 . Synthesis of Eicosanoids from Arachidonic acid Source: Author, ILLL in house b. Transport All water-soluble hormones are carried dissolved in plasma without any transport proteins. Institute of Life Long Learning, University of Delhi 13 Hormones: An overview Value addition: Did you Know Heading: How aspirin works Though Aspirin (acetylsalicylic acid) has been used as an anti-inflammatory analgesic for centuries, it was only in 1974 that John Vane discovered its mode of action. Aspirin works by inhibiting the enzyme responsible for the synthesis of prostaglandins that are involved in pain and inflammation. Source: Author Mode of Action of Hormones Hormones manifest their effect by binding to specific receptors. These receptors are intracellular for lipid-soluble hormones as these hormones can readily cross the lipid plasma membrane. For water-soluble hormones, the receptors are present on the cell surface since these hormones cannot cross the lipid plasma membrane of the cell. As the hormone binds to its receptor, it activates the receptor to give rise to an activated receptor-hormone complex. The sequence of events resulting in the ultimate response to the hormone, starting with the formation of the activated hormone-receptor complex, is known as the signal transduction pathway (where, hormone is the signal and the sequence of events culminating in the response is the transduction). Action of lipid-soluble hormones Lipid-soluble hormones act directly by binding to intracellular receptors. Steroid hormones have receptors in the cytoplasm while thyroid hormones have receptors present inside the nucleus (Figure 8). Institute of Life Long Learning, University of Delhi 14 Hormones: An overview Fig. 8 . Action of steroids hormones Source: http://upload.wikimedia.org/wikipedia/commons/a/a9/1803_Binding_of_Lipid- Soluble_Hormones.jpg The action of these hormones can be shown by the following flow chart: Institute of Life Long Learning, University of Delhi 15 Hormones: An overview Value addition: Video Heading: Mechanism of action of steroid hormone Learn more about the mechanism of action of lipid soluble steroid hormones: https://www.youtube.com/watch?v=Nm9u4lNCPyM EMBEDTHE VIDEO Source: YouTube Action of water-soluble hormones Water-soluble hormones bind to extracellular portions of transmembrane receptors For water-soluble hormones, the receptors usually are transmembrane proteins with a part of the receptor on the outer surface on the cell where the hormone binds and a part Institute of Life Long Learning, University of Delhi 16 Hormones: An overview protruding on the inner side of the cell membrane, which is responsible for bringing about the effect of the hormone. Fig. 10. Action of water soluble hormones Source: http://cnx.org/content/m46667/latest/1804_Binding_of_WaterSoluble_Hormones.jpg The inner portions of the membrane receptors for water-soluble hormones may act in different ways to bring about the hormone-response: Institute of Life Long Learning, University of Delhi 17 Hormones: An overview 1. These receptors may directly function as enzymes that bring about a change in the cell e.g. Receptor tyrosine kinases that cause phosphorylation of its own tyrosine- containing portions refer to Video 1). Video 1. Action of tyrosine-kinase receptors. Signal molecule is the water-soluble hormone. EMBEDTHE VIDEO Source: ILLL in house Action of receptor tyrosine-kinases can be summarized as follows: Extracellular portion of the receptor + hormone Activated receptor-hormone complex Phosphorylation of the tyrosine groups in the intracellular portion of the receptor protein Binding of another intracellular protein to the phosphorylated receptor protein Phosphorylation of the intracellular protein Such a pathway exists for Institute of Life Long Learning, University of Delhi Stimulation 18of a cellular activity Growth Hormones: An overview Factors which stimulate cell proliferation and differentiation 2. These receptors may be associated with another group of cytoplasmic tyrosine kinases called the Janus Kinases (JAKs). Different JAKs phosphorylate different proteins which act as transcription factors stimulating synthesis of specific proteins. The signal transduction pathway for these receptors is given below: 3. They are most commonly associated with a hetero-trimeric protein, the G-protein (GTP-binding protein) and therefore, these Institute of Life Long Learning, University of Delhi 19 Hormones: An overview receptors are called G-protein-coupled receptors. The G-protein may cause opening of certain ion channels e.g. Ca2+ ion channels or it may stimulate or inhibit an enzyme. Activation of enzymes causes the formation of a second messenger usually cAMP (cyclic Adenosine Mono Phosphate) which then brings about the hormone response (see Figure 9) through a series of events shown below: Institute of Life Long Learning, University of Delhi 20 Hormones: An overview Extracellular portion of the receptor + hormone Activated receptorhormone complex Intracellular (G-proteincoupled) part of the receptor undergoes a conformational change G –protein exchanges GDP with GTP G-protein gets associated with another intracellular protein e.g. enzyme Adenylyl (or adenylate) cyclase and activates it Activated Adenylyl Cyclase Cyclic AMP (cAMP) Cytoplasmic ATP Degrades Phosphodiesterase Activates cAMPdependent Protein Kinase Activated Protein Kinase Phosphorylated Enzyme 1 Enzyme 1 A cellular activity is STIMULATED (Stimulatory action of the hormone) Phosphorylated Enzyme 2 A cellular activity is INHIBITED (Inhibitory action of the hormone) Institute of Life Long Learning, University of Delhi 21 Enzyme 2 Hormones: An overview Those G-proteins that result in stimulation of a cellular activity are called stimulatory Gproteins and those causing inhibition of a cellular activity are called inhibitory G-proteins. Fig.9: Action of G-protein-coupled receptors Source: http://www.rci.rutgers.edu/~uzwiak/AnatPhys/PPFall03Lect8_files/image002.jpg permission Institute of Life Long Learning, University of Delhi 22 written for Hormones: An overview Cyclic AMP (cAMP) is known as the second messenger as it brings about the response to the hormone which is the first messenger. Cyclic AMP lasts for a limited period of time after which it is destroyed by an intracellular enzyme, phosphodiesterase. For the action of the hormone to continue, new molecules of the hormone need to bind to the receptors to keep generating new cAMP. In addition to cAMP, other molecules like Ca2+ ions, inositol triphosphate (IP3), diacylglycerol (DAG) and cyclic guanosine monophosphate (c GMP) are also used as second messengers. The steps in the signal transduction pathway occur in succession, each initiating or triggering the next step; one molecule activates another, which in turn activates another forming a cascade of events. The reaction is amplified at each step as each molecule activates hundreds of molecules with each activated molecule further activating hundreds of another type of molecule. Click the link and find out how the cAMP brings the response to hormone http://www.youtube.com/watch?v=A3AUhMCE9n0 The responsiveness of the target cell to a particular hormone keeps changing from time to time because the number of receptors for the hormone keeps changing. Generally, when the concentration of the hormone increases resulting in an increased number of receptors binding with the hormone, the cell responds by reducing the number of receptors. This is achieved by internalization (where the receptor is taken inside the cell and is not available for binding with the hormone), their destruction by lysosomes, and reduced production. This process of reduction in the number of receptors following an increase in the hormone levels is known as down regulation. Similarly, there may be an up regulation of the receptors by causing an increase in the number of receptors or an increased responsiveness of the cell to the hormone by increasing the synthesis of intracellular signaling molecules. Regulation of Hormone Secretion Hormones are secreted in short bursts and their concentration varies with the 24-hour cycle, with age, season and state of sleep e.g., growth hormone levels rise during early stages of Institute of Life Long Learning, University of Delhi 23 Hormones: An overview sleep. The levels of hormones are regulated by negative and positive feedback mechanisms with inputs from 1) Neurons 2) Chemical changes in the blood and 3) Other hormones. When the concentration of a hormone increases beyond a specific level it inhibits its own secretion by inhibiting the stimulus that caused its secretion. This is known as negative feedback regulation (Fig. 10). Stimulus Endocrine Gland Hormone Secretion Increased hormone levels Negative Feedback (inhibition) Fig.10. Negative feedback inhibition Source: Author, ILLL in house A positive feedback serves to increase the levels of a hormone e.g., during childbirth, the levels of oxytocin keep increasing due to stretching of the cervix caused by uterine contractions induced by oxytocin itself. The positive feedback cycle is broken by the event of childbirth (Figure 11). Specific feedback mechanisms for regulating the secretion of different hormones will be discussed in the subsequent chapters. Click the link and find out about the positive and negative feedback regulation of hormone Institute of Life Long Learning, University of Delhi 24 Hormones: An overview Fig.11. Positive feedback loop for oxytocin secretion during childbirth Source: OpenStax College. Homeostasis. OpenStax-CNX. 3 June <http://cnx.org/content/m45989/1.3/>. http://cnx.org/content/m45989/latest/106_Pregnancy-Positive_Feedback.jpg CC Institute of Life Long Learning, University of Delhi 25 2013 Hormones: An overview Hormone Interactions Actions of a hormone on a target cell can be modified by another hormone. Depending on the ways in which hormones interact with each other, two or more hormones together can have a: Permissive effect- where exposure to a specific hormone is necessary before another hormone can act on the target cell. Here, the first hormone either causes the development of receptors for the second hormone to act or it causes the synthesis of some enzymes required for the action of the second hormone e.g. uterine cells have to be exposed to estrogen before they can respond to progesterone because they develop progesterone receptors only when exposed to estrogen. Synergistic effect- when two hormones together can bring about a certain effect which either one alone cannot e.g., development of ovarian follicles is brought about together by FSH and estrogens and either of these alone cannot achieve that. Antagonistic effect- where one hormone has an effect opposite to another hormone e.g., calcitonin (hormone from the parafollicular cells of the thyroid gland) reduces blood calcium levels while parathyroid hormone (hormone from the parathyroid glands) increases them. Institute of Life Long Learning, University of Delhi 26 Hormones: An overview Summary Body functions are regulated by the endocrine system, the nervous system and the interface between the two (neuroendocrine mechanisms) Endocrine glands are ductless glands that release their secretions (hormones) directly into the blood stream from where they are carried to the various target organs. Hormones regulate various activities like metabolism and energy balance, contractile activities of muscles, secretory activities of glands, immune system activities etc. Types of Hormones Depending upon their solubility, hormones can be of two types--Lipid-soluble and watersoluble hormones. 1) Lipid-soluble hormones are not soluble in water. They include: • Steroid hormones- sex hormones and hormones of the adrenal cortex. They are synthesized from cholesterol and transported in the blood bound to specific plasmaproteins. • Thyroid hormones- Tri-iodothyronine and thyroxine. These are iodinated molecules derived from the amino acid tyrosine. They are transported in the blood bound to thyroxine binding globulin. • Nitric Oxide (NO) - This is a gas which is synthesized from the amino acid arginine by the activity of the enzyme Nitric Oxide Synthase (NOS). It is transported in the blood bound to hemoglobin and other proteins. 2) Water-soluble hormones include: • Peptides and proteins- hormones containing less than 100 amino acids are called peptides (e.g., oxytocin and vasopressin) and those with more than 100 amino acids are called proteins (e.g., growth hormone).These hormones are synthesized as inactive preprohormones by the rough endoplasmic reticulum and later modified into their active forms. • Biogenic amines- they are derived from amino acids and retain an amino group. These include catecholamines (epinephrine, nor-epinephrine and dopamine) derived from the amino acid tyrosine. Serotonin and melatonin are derived from the amino acid tryptophan. • Eicosanoids-hormones derived from a 20-carbon fatty acid, arachidonic acid. These include prostaglandins, thromboxanes and leukotrienes. Institute of Life Long Learning, University of Delhi 27 Hormones: An overview All water-soluble hormones are transported by blood in their dissolved form (dissolved in plasma). Mode of Action of hormones Lipid-soluble hormones act on their target cells by binding to intracellular receptors as they can cross the lipid membrane. Steroid hormones bind to receptors in the cytoplasm while thyroid hormones bind to receptors present inside the nucleus. The hormonereceptor complex (activated) then binds to specific regulatory sequences of DNA activating or inhibiting specific genes. This results in stimulation or inhibition of a cellular activity through stimulation or inhibition of mRNA synthesis. Water-soluble hormones act by binding to receptors on the surface of the target cells as these hormones cannot cross the lipid membrane. The intracellular portions of the receptors act in different ways to bring about the hormone response: • They may act as an enzyme (tyrosine kinase) to cause its own phoshorylation resulting in stimulation (or inhibition) of a cellular activity e.g., receptors for growth factors • They may activate cytoplasmic tyrosine kinases like Janus Kinases (JAK) that phosphorylate other cytoplasmic proteins. These phosphorylated proteins act as transcription factors stimulating protein synthesis that brings about a change in cellular activities e.g., receptors for the hormone leptin from adipose tissue. • They are most commonly associated with the GTP-binding protein, the G-Protein, hence these receptors are known as the G-Protein-coupled receptors. The G-Protein may directly bring about a change by causing opening or closing of certain ion channels or it may activate an enzyme (e.g., Adenylate cyclase) resulting in the formation of a second messenger, cyclic-AMP which then brings about the response The responsiveness of a target cell to a hormone keeps changing depending upon the number of receptors that may increase with a reduction in the hormone concentration (up-regulation) or decrease with an increase in the hormone concentration (downregulation). Regulation of hormone secretion Institute of Life Long Learning, University of Delhi 28 Hormones: An overview Hormone levels are regulated by negative feedback mechanisms with inputs from the nervous system, other hormones and chemical changes in blood. When the concentration of a hormone increases beyond a level it inhibits its own secretion by a negative feedback. When its concentration falls below a certain level it stimulates its own secretion by a positive feedback. Hormone Interactions One or more hormones may interact with each other to produce an effect. These are: • Permissive effect- where action of one hormone is necessary before another hormone can act on the target cells • Synergistic effect- where two or more hormones together can bring about a response that each one of them alone cannot. • Antagonistic effect- when one hormone has an effect opposite to that of another hormone Glossary Institute of Life Long Learning, University of Delhi 29 Hormones: An overview Adrenocorticotropin - (ACTH or corticotropin) anterior pituitary, peptide hormone Antidiuretic hormone - (ADH) hypothalamus, peptide hormone Atrial natriuretic factor - (ANP) heart, , peptide hormone Autocrine agents: Chemicals secreted by a cell or tissue that act on the same cell or tissue that produces it. Biogenic amines: Hormones derived from amino acids tyrosine and tryptophan are called biogenic amines as they retain an amino group. These include catecholamines (epinephrine, nor-epinephrine and dopamine that are derived from amino acid tyrosine), serotonin and melatonin, both derived from amino acid tryptophan. Calcitonin - (CT) C cells of thyroid, peptide hormone Corticosteroid binding globulin - (CBG) binds and transports glucocorticoids in the plasma. Globin is synthesized in the liver. Down-regulation: Reduction in the number of receptors for a hormone when the hormone concentration is high. Eicosanoids: These are the hormones derived from a 20-carbon fatty acid, arachidonic acid. These include prostaglandins, thromboxanes and leukotrienes Endocrine glands: Ductless glands that pour their secretions (hormones) into the blood stream. Follicle stimulating hormone - (FSH) pituitary, protein hormone G-protein: A hetero-trimeric, GTP-binding protein associated with receptors for water-soluble hormones that bring about the formation of a second messenger like cyclic AMP. G-protein-coupled receptors: Receptors for water-soluble hormones that are associated with G-proteins. Growth hormone - (GH) pituitary, peptide hormone Hormones: Chemical substances secreted by ductless glands and released into the blood stream. Human chorionic gonadotropin - (hCG) pancreas glycoprotein hormone with 2 subunits (alpha and beta joined non covalently). Similar in structure to luteinizing Institute of Life Long Learning, University of Delhi 30 Hormones: An overview hormone (LH), hCG exists in multiple hormonal and non-endocrine agents (regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG). Janus kinases: These are a type of cytoplasmic tyrosine kinases which are activated by the receptors for the water-soluble hormones. They bring about phosphorylation of specific cytoplasmic proteins affecting a cellular activity. Lipid-soluble hormones: Hormones that are soluble in lipids and insoluble in water e.g., steroid hormones. They need specific plasma-proteins to be transported in the blood as they are not soluble in blood plasma. Luteinizing hormone - (LH) pituitary, protein hormone Melanocyte stimulating hormone - (MSH) pituitary, peptide hormone Negative feedback: When the concentration of a hormone increases beyond a specific level it inhibits its own secretion by inhibiting the stimulus that caused its secretion. This is known as negative feedback regulation. Nitric Oxide: A gas which acts as a hormone and a neurotransmitter and is synthesized when needed from the amino acid arginine by the activity of enzyme nitric oxide synthase. Paracrine agents: Chemicals secreted by a cell or tissue that act on the neighboring cells to modify their activity. Parathyroid hormone - (PTH) parathyroid, peptide hormone Positive feedback: When the levels of a hormone are low, it enhances its own secretion by stimulating the mechanisms causing its secretion. This is known as positive feedback regulation. Preprohormones: Protein and peptide hormones are synthesized by the rough endoplasmic reticulum as inactive precursors called preprohormones that are variously modified to form the active hormones. Prohormones: During the synthesis of protein and peptide hormones, a part of the preprohormone (the inactive precursor) is cleaved by the endoplasmic reticulum to form a prohormone which is then converted into an active hormone. Prolactin - (PRL) pituitary, peptide hormone Protein and peptide hormones: Hormones consisting of 3 to 100 amino acids are called peptide hormones while those containing more than 100 amino acids are called protein hormones e.g., growth hormone. Institute of Life Long Learning, University of Delhi 31 Hormones: An overview Receptor tyrosine kinases: Receptors for water-soluble hormones that directly function as enzymes causing phosphorylation of tyrosine-containing portions of itself. Second messengers: Molecules like cyclic AMP, diacylglycerol and inositol triphosphate that are formed as a result of binding of a water-soluble hormone (first messenger) to its receptor on the cell surface. Second messengers bring about the response of the hormone. Signal transduction pathway: The sequence of events resulting in the ultimate response to a hormone in its target cell. Steroid hormones: Lipid-soluble hormones derived from cholesterol. For example, the sex hormones (estrogen, progesterone and testosterone) and the hormones of the adrenal cortex (cortisol, aldosterone and androgens). Thyroid hormone - (TH) thyroid, amino acid derivative. Thyroid hormones: Hormones of the thyroid gland-- Tri-iodothyronine and tetraiodothyronine (thyroxine). These are formed by coupling of iodinated tyrosine molecules. Thyroid stimulating hormone - (TSH) pituitary, protein hormone Up-regulation: Increase in the number of receptors for a hormone when the hormone concentration is low. Water-soluble hormones: Hormones like oxytocin, growth hormone and epinephrine that are soluble in water and can be transported in the blood without any transport proteins. Exercises A. Multiple-choice questions Q1 Hormones are secreted by Institute of Life Long Learning, University of Delhi 32 Hormones: An overview a) Endocrine glands b) Exocrine glands c) Extracellular tissue d) Connective tissue Q2 Which of the following contribute to homeostasis a) Endocrine glands b) Nervous system c) Neuroendocrine mechanisms d) All of these Q3 Hormones are transported by a) Blood b) Lymph c) Neurons d) Cells Q4 The advantage of release of hormones into the bloodstream and their transport by blood is that they can a) reach distant target organs/cells b) act on multiple target organs/cells c) bind to blood cells d) both a and b Q5 Paracrine agents act on a) distant target organs/cells b) neighboring organs/cells c) same organ/cells d) none these Q6 Autocrine agents act on a) neighboring organs/cells b) same organ/cells c) distant target organs/cells d) none these Q7 Steroid hormones are a) lipid-soluble Institute of Life Long Learning, University of Delhi 33 Hormones: An overview b) derived from cholesterol c) not stored in their ready form d) all of these Q8 Thyroxine is not a) lipid-soluble b) derived from tyrosine c) stored in the thyroid follicle bound to thyroglobulin d) transported dissolved in plasma Q9 Plasma proteins that carry lipid-soluble hormones in the blood do not a) increase their half-life b) provide a ready stock of hormones c) prevent them from being excreted by the kidney d) decrease their efficacy Q10 Peptide hormones are not a) made of more than 100 amino acid residues b) synthesized by the rough endoplasmic reticulum c) synthesized as inactive preprohormones d) all of these Q11 Epinephrine is not a a) biogenic amine b) catecholamine c) water-soluble hormone d) tryptophan derivative Q12 Nitric oxide is a) synthesized from amino acid tyrosine b) same as endothelium derived relaxation factor c) water soluble d) stored as a neurotransmitter Q13 Eicosanoids are a) derived from a 10-carbon fatty acid b) lipid-soluble c) prostaglandins, thromboxanes and leukotrienes Institute of Life Long Learning, University of Delhi 34 Hormones: An overview d) none of these Q14 Receptors for water-soluble hormones are present a) inside the cytoplasm b) inside the nucleus c) on the cell surface d) on the nuclear membrane Q15 Second messengers are required for the action of a) lipid-soluble hormones b) water-soluble hormones c) steroid hormones d) thyroid hormones B. Short-answer questions Q1 Differentiate between the role of nervous system and the endocrine system as homeostatic systems. Q2 How are lipid-soluble hormones transported in the blood? Q3 How does aspirin work as a pain killer? Q4 What are catecholamines? Q5 Why are thyroid hormones lipid-soluble and catecholamines water-soluble when both are derived from tyrosine? Q6 What is meant by a ‘signal transduction pathway’? Q7 What are second messengers? Q8 Describe the negative and positive feedback regulation of hormones. Q9 How is nitric oxide synthesized and transported? Q10 Differentiate between up-regulation and down-regulation. C. Long-answer questions Q1 Describe the various hormones based on their solubility in blood plasma. Q2 How do lipid-soluble hormones act on their target cells? Q3 Discuss the mode of action of water-soluble hormones. Q4 How are hormone levels regulated in the body? Institute of Life Long Learning, University of Delhi 35 Hormones: An overview Q5 How do hormones interact with each other to modify their actions? References Tortora, G.J. and Derrickson, B.H. (2009). Principles of Anatomy and Physiology, XII Edition, John Wiley and Sons, Inc. Widmaier, E.P., Raff, H. and Strang, K.T. (2008). Vander’s Human Physiology, XI Edition, McGraw Hill Guyton, A.C. and Hall, J.E. (2011). Textbook of Medical Physiology, XII Edition, Harcourt Asia Pvt. Ltd/ W.B. Saunders Company Weblinks http://www.hartnell.edu/tutorials/biology/signaltransduction.html Institute of Life Long Learning, University of Delhi 36