Introduction to Endocrinology Lecture 1 2024 PDF

Endocrine and Reproductive physiology LECTURE ONE DR. HANAN AL- TAEE DEPARTMENT OF PHYSIOLOGY https://classroom.google.com/c/NzE3ODYwMzkwMzkw?cjc=clb4gxy INTRODUCTION TO ENDOCRIN...

Endocrine and Reproductive physiology LECTURE ONE DR. HANAN AL- TAEE DEPARTMENT OF PHYSIOLOGY https://classroom.google.com/c/NzE3ODYwMzkwMzkw?cjc=clb4gxy INTRODUCTION TO ENDOCRINOLOGY: Objectives: 1. To know the control of the body activities. 2. Define hormones and describe their chemical structure. 3. Explain the mechanisms of hormone secretion and action. 4. Discuss the control of hormone secretion. Endocrine physiology is concerned with the maintenance of various aspects of homeostasis. The mediators of such control mechanisms are soluble factors known as hormones. Major hormonal contributors to homeostasis. The endocrine system is a distributed system of glands and circulating messengers that is often stimulated by the central nervous system or the autonomic nervous system, or both. All the physiological activities of the body are regulated by two major systems: 1. Nervous system. 2. Endocrine system. These two systems interact with one another and regulate the body functions through chemical messengers which may be secreted from the cells of several other tissues. Chemical messengers are substances involved in cell signaling, are classified into four types: 1. Endocrine messengers. 2. Paracrine messengers. 3. Autocrine messengers. 4. Neurocrine messengers. 1. Endocrine messengers: are the classical hormones. A hormone is defined as a chemical messenger, synthesized by endocrine glands and transported by blood to the target organs or tissues (site of action). Examples are growth hormone and insulin. 2. Paracrine Messengers: Paracrine messengers are the chemical messengers, which diffuse from the control cells to the target cells through the interstitial fluid. Some of these substances directly enter the neighboring target cells through gap junctions. Such substances are also called juxtacrine messengers or local hormones. Examples are prostaglandins and histamine. 3. Autocrine Messengers: Autocrine messengers are the chemical messengers that control the source cells which secrete them. So, these messengers are also called intracellular chemical mediators. Examples are leukotrienes. 4. Neurocrine or Neural Messengers: Neurocrine or neural messengers are neurotransmitters and neurohormones (Fig. 1). Neurotransmitter is an endogenous signaling molecule that carries information form one nerve cell to another nerve cell or muscle or another tissue. Examples are acetylcholine and dopamine. Neurohormone is a chemical substance that is released by the nerve cell directly into the blood and transported to the distant target cells. Examples are oxytocin, antidiuretic hormone and hypothalamic releasing hormones. FIGURE(1):Demonstrating types of chemical messengers. Some of the chemical mediators act as more than one type of chemical messengers. For example, noradrenaline and dopamine function as classical hormones as well as neurotransmitters. Similarly, histamine acts as neurotransmitter and paracrine messenger. The endocrine hormones are carried by the circulatory system to cells throughout the body, including the nervous system in some cases, where they bind with receptors and initiate many reactions. Some endocrine hormones affect many different types of cells of the body; for example, growth hormone (from the anterior pituitary gland) causes growth in most parts of the body, and thyroxine (from the thyroid gland) increases the rate of many chemical reactions in almost all the body’s cells. Other hormones affect only specific target tissues, because only these tissues have receptors for the hormone. For example, adrenocorticotropic hormone (ACTH) from the anterior pituitary gland specifically stimulates the adrenal cortex, causing it to secrete adrenocortical hormones; and the ovarian hormones have specific effects on the female sex organs as well as on the secondary sexual characteristics of the female body. ENDOCRINE GLANDS Endocrine glands are the glands which synthesize and release the classical hormones into the blood, they are also called ductless glands because the hormones secreted by them are released directly into blood without any duct. Endocrine glands play an important role in homeostasis and control of various other activities in the body through their hormones. (FIGURE )2  FIGURE(2): Major endocrine glands. The multiple hormone systems play a key role in regulating almost all body functions, including metabolism, growth and development, water and electrolyte balance, reproduction and behavior. Transport: After secretion of hormones, small fraction will circulate freely(Proteins/peptides: water soluble thus transported by plasma in soluble form without carrier (some exceptions- IGF binding proteins, GH binding proteins) and the major part will bind to plasma protein(albumin or globulin) which acts as: 1- Storage site, release the hormone on need. 2-Buffer mechanism: to minimize the effect of particular hormones. Steroids/thyroid hormones CHEMISTRY OF HORMONES Based on chemical nature, hormones are classified into three types 1. Steroid hormones 2. Protein hormones 3. Derivatives of the amino acid called tyrosine. STEROID HORMONES Steroid hormones are the hormones synthesized from cholesterol or its derivatives. Steroid hormones are secreted by adrenal cortex, gonads and placenta. PROTEIN HORMONES Protein hormones are large or small peptides. Protein hormones are secreted by pituitary gland, parathyroidglands, pancreas and placenta (4‘P’s). Growth hormone (GH) ,Thyroid-stimulating hormone (TSH), Adrenocorticotropic hormone (ACTH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Prolactin, Antidiuretic hormone (ADH), Oxytocin, Parathormone, Calcitonin, Insulin, Glucagon, Somatostatin, Pancreatic polypeptide, Human chorionic gonadotropin (HCG)and Human chorionic somatomammotropin. TYROSINE DERIVATIVES Two types of hormones, namely thyroid hormones and adrenal medullary hormones are derived from the amino acid tyrosine. Onset of Hormone Secretion: After a Stimulus, some hormones, such as norepinephrine and epinephrine, are secreted within seconds after the gland is stimulated, and they may develop full action within another few seconds to minutes; the actions of other hormones, such as thyroxine or growth hormone, may require months for full effect. HORMONAL ACTION: Hormone does not act directly on target cells. First it combines with receptor present on the target cells and forms a hormone-receptor complex. This hormone receptor complex induces various changes or reactions in the target cells. HORMONE RECEPTORS Hormone receptors are the large proteins present in the target cells. Each cell has thousands of receptors. Important characteristic feature of the receptors is that, each receptor is specific for one single hormone, i.e. each receptor can combine with only one hormone. Thus, a hormone can act on a target cell, only if the target cell has the receptor for that particular hormone. Situation of the Hormone Receptors: (Fig. 3). 1. Cell membrane: Receptors of protein hormones and adrenal medullary hormones (catecholamines) are situated in the cell membrane. 2. Cytoplasm: Receptors of steroid hormones are situated in the cytoplasm of target cells. 3. Nucleus: Receptors of thyroid hormones are in the nucleus of the cell and are believed to be located in direct association with one or more of the chromosomes.  Figure (3): site of Hormone Receptors Receptor proteins are not static components of the cell. Their number increases or decreases in various conditions. Generally, when a hormone is secreted in excess, the number of receptors of that hormone decreases due to binding of hormone with receptors. This process is called down regulation. Examples: Pituitary insensitivity to GnRH after continuous infusion or long acting analogs During the deficiency of the hormone, the number of receptor increases, this is called up regulation. This serves to maximize the effect of the reduced hormone levels on the tissue. Example: Increased GH receptors in GH deficiency. MECHANISM OF HORMONAL ACTION: This complex executes the hormonal action by one of the following mechanisms: 1. By altering permeability of cell membrane (ach) Acetylcholine increases the permeability of the postsynaptic membrane for sodium, by opening the ligand- gated sodium channels. So, sodium ions enter the neuromuscular junction from ECF through the channels and cause the development of endplate potential. 2. Protein hormones and the catecholamines act by activating the intracellular enzymes. The hormone which acts on a target cell is called first messenger or chemical mediator. It combines with the receptor and forms hormone-receptor complex. Hormone-receptor complex activates the enzymes of the cell and causes the formation of another substance called the second messenger or intracellular hormonal mediator. Second messenger produces the effects of the hormone inside the cells. Protein hormones and the catecholamines act through second messenger. Most common second messenger is cyclic AMP. Cyclic AMP Cyclic AMP, cAMP or cyclic adenosine 3’5’-monophosphate acts as a second messenger for protein hormones and catecholamines. Formation of cAMP – Role of G proteins G proteins or guanosine nucleotide-binding proteins are the membrane proteins situated on the inner surface of cell membrane. These proteins play an important role in the formation of cAMP Sequence of events in the formation of c AMP( figure 4). i. Hormone binds with the receptor in the cell membrane and forms the hormone- receptor complex ii. It activates the G protein iii. G protein releases GDP from α-GDP unit.  Figure (4): Mode of action of protein hormones and catecholamines. H = Hormone. R = Receptor, α, β, γ = G protein, GDP = Guanosine diphosphate, GTP = Guanosine triphosphate, ECF = Extracellular fluid, cAMP = Cyclic adenosine 3’5’-monophosphate, ATP = Adenosine triphosphate Cyclic AMP produces the response, depending upon the function of the target cells through these enzymes. Response produced by cAMP Cyclic AMP produces one or more of the following responses: i. Contraction and relaxation of muscle fibers ii. Alteration in the permeability of cell membrane iii. Synthesis of substances inside the cell iv. Secretion or release of substances by target cell v. Other physiological activities of the target cell. 3. By acting on genes. (Thyroid hormones and steroids) Thyroid and steroid hormones execute their function by acting on genes in the target cells. Sequence of Events during Activation of Genes i. Hormone enters the interior of cell and binds with receptor in cytoplasm (steroid hormone) or in nucleus (thyroid hormone) and forms hormone receptor complex ii. Hormone-receptor complex moves towards the DNA and binds with DNA iii. This increases transcription of mRNA iv. The mRNA moves out of nucleus and reaches ribosomes and activates them v. Activated ribosomes produce large quantities of proteins vi. These proteins produce physiological responses in the target cells. Control of hormonal secretion A. Feedback mechanism: 1. Negative Feedback mechanism: a. direct: It relates the rate of release of the hormone to the blood concentration of that substance. After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone tend to suppress its further release, to prevent over secretion of the hormone or overactivity at the target tissue. eg. ACTH synthesized and released from the anterior lobe of the pituitary gland, secreted directly to the circulation and carried by the blood to affect the target organ, the suprarenal cortex, to secret cortisol. As the level of cortisol increased in the circulation it feeds back to the anterior pituitary and inhibit the release of ACTH, so no more stimulation of the adrenal cortex happen and no more cortisol secreted. b- Indirect negative feedback: This type will act when the nervous system (Hypothalamus) is involved in the process: e.g: CRH (corticotropic releasing hormone) released from the hypothalamus transported to the anterior lobe of pituitary; it stimulates the synthesis and release of ACTH. As the level of cortisol increase, it feeds back to the hypothalamus and it inhibits the release of ACTH which inhibits the secretion of cortisol. So ACTH affects the release of cortisol via CRH (indirect feedback). C- Short negative feedback: The hypothalamus controls the release of adenohypophysial hormones (anterior pituitary) by secreting releasing substances, some of these adenohypophysial hormones have feedback effect on the release of hypothalamic hormones, this is called short feedback loop e.g: GHRH (growth hormone releasing hormone), secreted from the hypothalamus and carried by blood (portal system) to the adenohypophysis, stimulates the synthesis and secretion of GH (growth hormone) which affects almost all body tissues and there is no hormone released in response to it (no target gland). If GH increases in the circulation, it feeds back to the hypothalamus and inhibits the release of GHRH, followed by inhibition of GH secretion, so called short feedback because the distance between the hypothalamus and pituitary is short. 2- Positive feedback mechanism: Means increase in the release of particular in hormone from a concerned gland in response to the increase in the increased chemical substance. e.g: FSH (follicular stimulation hormone) secreted by the pituitary gland, circulates in the blood to affect the ovary in the female and stimulates the development of ovarian follicle which will secrete estrogen (female sex hormone), as estrogen increases, it feeds back to the anterior pituitary, stimulates the release of LH and more FSH (LH and FSH responsible for the final maturation of the ovarian follicle). This happens in the first half of the menstrual cycle. B- Influence of the nervous system; Means the activity of the supplying nerve to the endocrine glands. The glands that are primarily controlled by the nervous system are: 1- Adrenal medulla. 2- Posterior lobe of the pituitary gland. There is what is called Cyclical Variation occur in hormone release, which are periodic variations in hormone release that are influenced by seasonal changes, various stages of development and aging, the diurnal (daily) cycle, and sleep. For example, the secretion of growth hormone is markedly increased during the early period of sleep but is reduced during the later stages of sleep. In many cases, these are due to changes in activity of neural pathways involved in controlling hormone release. Half-life of the Hormones Half-life is defined as the time during which half the quantity of a hormone, drug or any substance is metabolized or eliminated from circulation by biological process. It is also defined as the time during which the activity or potency of a substance is decreased to half of its initial value. Half life is also called biological half life.Half life of a hormone denotes the elimination of that hormone from circulation. STUDY OF ENDOCRINE DISORDERS An endocrine disorder is studied by analyzing: 1. Causes 2. Signs and symptoms 3. Syndrome. 1. Causes Endocrine disorder may be due to the hyperactivity or hypoactivity of the concerned gland. Secretion of hormones increases during hyperactivity and decreases during hypoactivity. 2. Signs and Symptoms A sign is the feature of a disease as detected by the doctor during the physical examination. So, it is the objective physical evidence of disease found by the examiner. Examples of signs are yellow coloration of skin and mucous membrane in jaundice, paleness in anemia, enlargement of liver, etc. A symptom is the feature of a disease felt by the patient. So, it is the subjective evidence perceived by the patient. In simple words, it is a noticeable change in the body, experienced by the patient. Examples of symptoms are fever, itching, swelling, tremor, etc. 3. Syndrome: Syndrome is the combination of signs and symptoms (associated with a disease), which occur together and suggest the presence of a certain disease or the possibility of developing the disease. TYPES OF ENDOCRINE DISORDERS  Hormone deficiency  Hormone excess  Hormone resistance Endocrine pathology Primary Secondary Endocrine disorders can be diagnosed on the basis of  The symptoms they produce in concert. Observations &Clinical assessment: Height &weight Hands Skin Pulse &blood pressure Head Voice Body fat Bones Genitalia Legs  Investigation With appropriate biochemical testing of blood, Radioimmunoassays for specific hormones remain the mainstay of diagnostic endocrinolology and can be used to establish steady state concentrations as well as dynamic changes of the hormone in question but the circumstances in which the sample is taken are often crucial , especially for hormones with: who present with a tumour. Summary:  The endocrine system consists of a distributed set of glands and the chemical messengers that they produce, referred to as hormones. Hormones play a critical role in ensuring homeostasis (ie, the relative stability of body systems).  Hormones can be grouped into peptide/protein, amine, and steroid categories.  The synthesis and release of many hormones is subject to regulation by negative feedback loops.  Disease states can arise in the setting of both hormone deficiency and excess.