HORMON

What is hormon? Many organs in the body secreted biologically active compound called endocrine hormones, which are transported via blood stream to other tissues or organs where they exert a biological effect As classically defined, is a substance that is synthesized in one organ and transported by the circulatory system to act on another tissue Hormones can act on adjacent cells (paracrine) Hormones can act on the cell in which they were synthesized without entering the sistemic circulation (autocrine)

Long-Distance Regulators Animal hormones are chemical signals that are secreted into the circulatory system and communicate regulatory messages within the body Hormones reach all parts of the body, but only target cells are equipped to respond Hormones convey information via the bloodstream to target cells throughout the body

What is the importance of hormones? Several hormones may control one, process or one hormon may control several process Provide communication beetween cells, tissues and organs This comunication is responsible for the regulation of wide range of functions including growth, reproduction, development, homeostasis, and response to external stimuli. Failure in this comunication channels are common and lead to many diseases of the endocrine system

How do hormones act? In order to act , hormones must interact with other loci on or in the target cell These sites are termed receptors A receptor is a locus to which the hormone binds in order to elicit its action

RECEPTOR A receptor has two function : First, it must be able to distinguish the hormone from all the other chemicals present in the circulation and bind it. The hormone binding sites on receptors have evolved to have unique configurations that are complementary to the hormones they bind. Generally, hormone-receptor interactions are noncovalent in nature and are reversible.

RECEPTOR - Second, the receptor must able to transmit the information gained from the binding to trigger a cellular response. Thus, subtances that bind hormones, even tightly, but do not trigger subsequent responses are not receptors.

Types of Hormones Hormon can be clasisified in several ways, according: 1-Chemical composition : Cholesterol derivates– this include : glucorticoid, mineralocorticoid, esterogen, progestin Amino acid -tyrosine Polypeptyde-ACTH,TRH Glycoprotein-TSH, FSH, LH 2-Solubility properties-lipophilic dan hidrophilic 3-Location of reseptor 4-Nature of signaling used to mediate hormonal action within the cell

Clasification of hormones by mechanism of action Group I hormones Hormon that bind to intracellular receptors Androgens calcitriol esterogens glucocorticoids mineralocorticoids progestins retinoic acid

Group II Hormones Hormones that bind to cell surface receptors A.The second messenger is cAMP Calcitonin, glucagon, LH, Somatosatin, B.The second mesenger is cGMP Nitric oxide, atrial natriuretic factor C.The second messenger is calcium or phosphatidyl inositols (or both) Gastrin, oxitocyn, cholecistokinin, TRH, Acetilcholin D.The second messenger is a kinase or phosphatase cascade Adponectin, insulin , leptin, GH, Prolactin, IGF-I , IGF-II, EGF

General features of hormon classes Group I Group II Types Steroid, iodothyronines,calcitriol, retinoids Polypeptides, protein, glycoproteins, cathecolamines Solubility Lipophilic Hydrophilic Transport protein Yes No Plasma halflife Long ( hours to days) Short (minutes) Receptor Intracellular Plasma membran Mediator Receptor-hormone complex cAMP.cGMP, Ca2+,metabolites complex phosphoinositols, kinase cascade

WHERE HORMONES ARE SYNTHESIZED? Hormones are synthesized in discrete organs designed solely for spesific purpose Pituitary: TSH, FSH, LH, GH, Prolactin, ACTH Some organs are disigned to perform two distinct but closely related function Ovaries produce mature oocyte and reproductive hormones estradiol and progesteron The testes produce mature spermatozoa and testesterone Hormones are also produced in specialized cells within other organs Small intestine : glucagon like peptide Thyroid : calcitonin Kydney : angiotensin II The synthesis of some hormones requires the parenchimal cells of more than one organ Skin, liver, kidney : calcitriol.

Hormon are synthesized and modified for full activity in a variety of ways Some hormones are synthesized in final form and secreted immediattely , included in this class are the hormon derived from cholesterol Others are synthesized in final form and stored in producing cells, example catecholamine The others hormone synthesized and from precursor molecules in the producing cell, then are processed and secreted upon a physiologic cue, examples insulin Converted to active forms from precurssor molecules in the periphery, examples: T3, DHT

Control Pathways and Feedback Loops The endocrine system secretes hormones that coordinate slower but longer-acting responses including reproduction, development, energy metabolism, growth, and behavior A common feature is a feedback loop connecting the response to the initial stimulus Negative feedback regulates many hormonal pathways involved in homeostasis

Signaling by any of these hormones involves three key events: Reception Signal transduction Response

SECRETORY CELL SECRETORY CELL Hormone molecule Hormone molecule VIA BLOOD VIA BLOOD Signal receptor TARGET CELL TARGET CELL Signal transduction pathway Signal receptor OR Cytoplasmic response DNA Signal transduction and response mRNA DNA Nuclear response NUCLEUS Synthesis of specific proteins NUCLEUS Receptor in plasma membrane Receptor in cell nucleus

The same hormone may have different effects on target cells that have Binding of a hormone to its receptor initiates a signal transduction pathway leading to responses in the cytoplasm or a change in gene expression The same hormone may have different effects on target cells that have Different receptors for the hormone Different signal transduction pathways Different proteins for carrying out the response

Different receptors different cell responses Epinephrine Epinephrine Epinephrine a receptor  receptor  receptor Glycogen deposits Vessel dilates Glycogen breaks down and glucose is released from cell Vessel constricts Intestinal blood vessel Skeletal muscle blood vessel Liver cell Different intracellular proteins different cell responses

Paracrine Signaling by Local Regulators In paracrine signaling, nonhormonal chemical signals called local regulators elicit responses in nearby target cells Types of local regulators: Neurotransmitters Cytokines and growth factors Prostaglandins help regulate aggregation of platelets, an early step in formation of blood clots

The hypothalamus and pituitary integrate many functions of the vertebrate endocrine system The hypothalamus and the pituitary gland control much of the endocrine system Tropic hormones, hormones that regulate endocrine organs Tropic hormones are secreted into the blood and transported to the anterior pituitary

Hypothalamus Neurosecretory cells of the hypothalamus Axon Posterior pituitary Anterior pituitary HORMONE ADH Oxytocin TARGET Kidney tubules Mammary glands, uterine muscles

Neurosecretory cells of the hypothalamus Portal vessels Hypothalamic Tropic Effects Only FSH, follicle-stimulating hormone LH, luteinizing hormone TSH, thyroid-stimulating hormone ACTH, adrenocorticotropic hormone Neurosecretory cells of the hypothalamus Nontropic Effects Only Prolactin MSH, melanocyte-stimulating hormone Endorphin Portal vessels Nontropic and Tropic Effects Growth hormone Hypothalamic releasing hormones (red dots) Endocrine cells of the anterior pituitary Pituitary hormones (blue dots) HORMONE FSH and LH TSH ACTH Prolactin MSH Endorphin Growth hormone TARGET Testes or ovaries Thyroid Adrenal cortex Mammary glands Melanocytes Pain receptors in the brain Liver Bones

Posterior Pituitary Hormones The two hormones released from the posterior pituitary act directly on nonendocrine tissues Oxytocin induces uterine contractions and milk ejection Antidiuretic hormone (ADH) enhances water reabsorption in the kidneys

Anterior Pituitary Hormones The anterior pituitary produces both tropic and nontropic hormones

Tropic Hormones The four strictly tropic hormones are Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Each tropic hormone acts on its target endocrine tissue to stimulate release of hormone(s) with direct metabolic or developmental effects

Nontropic Hormones Nontropic hormones produced by the anterior pituitary: Prolactin stimulates lactation in mammals but has diverse effects in different vertebrates MSH influences skin pigmentation in some vertebrates and fat metabolism in mammals Endorphins inhibit pain

Growth Hormone Growth hormone (GH) has tropic and nontropic actions It promotes growth directly and has diverse metabolic effects It stimulates production of growth factors

The thyroid gland produces calcitonin, which functions in calcium homeostasis

Parathyroid Hormone and Calcitonin: Control of Blood Calcium Two antagonistic hormones, parathyroid hormone (PTH) and calcitonin, play the major role in calcium (Ca2+) homeostasis in mammals. Calcitonin stimulates Ca2+ deposition in bones and secretion by kidneys, lowering blood Ca2+ levels

Two Glands of Hormon Thyroid and parathyroid Located Produce hormone (PTH)

Calcitonin Thyroid gland releases calcitonin. Reduces Ca2+ uptake in kidneys Stimulates Ca2+ deposition in bones STIMULUS: Rising blood Ca2+ level Blood Ca2+ level declines to set point Homoeostasis: Blood Ca2+ level (about 10 mg/100 mL) Blood Ca2+ level rises to set point STIMULUS: Falling blood Ca2+ level Stimulates Ca2+ release from bones Parathyroid gland PTH Increases Ca2+ uptake in intestines Active vitamin D Stimulates Ca2+ uptake in kidneys

Insulin and Glucagon: Control of Blood Glucose The pancreas secretes insulin and glucagon, antagonistic hormones that help maintain glucose homeostasis Glucagon is produced by alpha cells Insulin is produced by beta cells

Alpha cells of pancreas release glucagon into the blood. Liver breaks Body cells take up more glucose. Insulin Beta cells of pancreas release insulin into the blood. Liver takes up glucose and stores it as glycogen. STIMULUS: Rising blood glucose level (for instance, after eating a carbohydrate- rich meal) Blood glucose level declines to set point; stimulus for insulin release diminishes. Homeostasis: Blood glucose level (about 90 mg/100 mL) Blood glucose level rises to set point; stimulus for glucagon release diminishes. STIMULUS: Dropping blood glucose level (for instance, after skipping a meal) Alpha cells of pancreas release glucagon into the blood. Liver breaks down glycogen and releases glucose into the blood. Glucagon

Target Tissues for Insulin and Glucagon Insulin reduces blood glucose levels by Promoting the cellular uptake of glucose Slowing glycogen breakdown in the liver Promoting fat storage

Glucagon increases blood glucose levels by Stimulating conversion of glycogen to glucose in the liver Stimulating breakdown of fat and protein into glucose

Diabetes Mellitus Diabetes mellitus is perhaps the best-known endocrine disorder It is caused by a deficiency of insulin or a decreased response to insulin in target tissues It is marked by elevated blood glucose levels

Adrenal Hormones: Response to Stress The adrenal glands are adjacent to the kidneys The adrenal medulla secretes epinephrine (adrenaline) and norepinephrine (noradrenaline) They are secreted in response to stress-activated impulses from the nervous system They mediate various fight-or-flight responses

Melatonin and Biorhythms The pineal gland, located in the brain, secretes melatonin Light/dark cycles control release of melatonin Primary functions of melatonin appear to relate to biological rhythms associated with reproduction

Invertebrate regulatory systems also involve endocrine and nervous system interactions Diverse hormones regulate homeostasis in invertebrates In insects, molting and development are controlled by three main hormones: Brain hormone stimulates release of ecdysone from the prothoracic glands Ecdysone promotes molting and development of adult characteristics Juvenile hormone promotes retention of larval characteristics

Hormones Released from the Anterior Pituitary or Adenohypophysis Somatotrophs Human Growth Hormone (hGH) Hypothalamic control hGH releasing hormone hGH inhibiting hormone Target Tissues: General body cells, particularly bone, muscle, cartilage, and the liver.

Hormones Released from the Anterior Pituitary or Adenohypophysis Hormone affects: promotes the synthesis of insulin-like growth factors Controls normal growth patterns by increasing protein synthesis, lipolysis, ATP production, and carbohydrate metabolism In adults, it help maintain muscle and bone mass and promote healing and tissue repair

Hormones Released from the Anterior Pituitary or Adenohypophysis Hypo-secretion: During childhood causes Dwarfism Hyper-secretion: During childhood causes Gigantism (up to 8 – 9 ft.) During Adulthood causes Acromegaly: Enlargement of the small bones of the hand and feet Enlargement of the cranium, nose, and lower jaw Tongue, liver, and kidneys become enlarged

Hormones Released from the Anterior Pituitary or Adenohypophysis Thyrotrophs: Thyroid Stimulating Hormone (TSH) Hypothalamic Control Thyrotropin Releasing Hormone (TRH) Target Tissue Follicular cells of the Thyroid gland Hormone affects: controls the production of T3 and T4

Endocrine activity of the Thyroid Gland Follicular cells: T3 and T4 Target Tissue; Almost all body tissues Hormone effects: Increases body metabolism Increases gluconeogenesis Increases glycolysis Increases lipolysis Increased basal metabolic rate (BMR) Increases heart rate and force of contraction

Endocrine activity of the Thyroid Gland Hypothyroidism: endemic goiter: (due to I2 deficiency) Myxedema: bagginess under the eyes and swelling of the face. Arteriosclerosis: due to increase in blood cholesterol Cretinism: extreme hypothyroidism during infancy and childhood

Endocrine activity of the Thyroid Gland Hypothyroidism: Cretinism: Physical and mental growth and development is greatly retarded Hyperthyroidism Toxic goiter Graves Disease with exophthalmos

Hormones Released from the Anterior Pituitary or Adenohypophysis Corticotrophs Adrenocorticotropic hormone (ACTH) Hypothalamic Control Corticotropic releasing hormone (CRH) Target Tissue Adrenal cortex, Zona Fasciculata Hormone affects: control production of glucocorticoids such as cortisol

Endocrine activity of the Adrenal Cortex Zona glomerulosa Mineralocorticoids such as Aldosterone Hormonal control renin-angiotensin pathway permissive effect of ACTH Target tissue: Principle cells of the DCT and collecting duct Hormone affects: increases reabsorption of Na+ and water

Endocrine activity of the Adrenal Cortex Hyper-secretion: Aldosteronism: Hypokalemia, increase in extracellular fluid and blood volume,and hypertension, may also have period of muscular paralysis Hypo-secretion: Addison’s disease Mineralocorticoids deficiency, death occurs in four days to two weeks if untreated

Endocrine activity of the Adrenal Cortex Zona Fasciculata Glucocorticoids such as cortisol and cortisone Hormone control: ACTH Target tissue: Liver and general body cells Hormone affects: Stimulates gluconeogenesis by the liver Decreased glucose utilization by cells

Endocrine activity of the Adrenal Cortex Hormone affects: Elevated blood glucose levels Reduction of protein stores in all body cells except the liver increased plasma protein levels promote lipolysis and beta oxidation of fat Helps body recover from stress Prevention of inflammation

Endocrine activity of the Adrenal Cortex Hypo-secretion Addison’s disease - glucocorticoid deficiency person becomes highly susceptible to disease and deteriorating effects of stress Hyper-secretion: Cushing’s Syndrome mobilization of fat from lower body to the thoracic and upper abdominal regions giving raise to “Buffalo Torso”

Interactions of hormones in response to stress

Endocrine activity of the Adrenal Cortex Zona reticularis Produces small amounts of androgens, mostly dehydroepiandosterone (DHEA), DHEA may be converted into estrogens Hormone Control: Believed to be ACTH Target tissue: General body cells

Endocrine activity of the Adrenal Cortex Hyper-secretion: Adrenogenital Syndrome in females causes beard growth, deeper voice, masculine distribution of body hair, and growth of the clitoris to resemble a penis. Picture: In pre-pubertal males it causes the rapid develop of secondary sexual conditions

Endocrine Activity of the Adrenal Cortex Hyper-secretion: Adrenogenital Syndrome in females causes beard growth, deeper voice, masculine distribution of body hair, and growth of the clitoris to resemble a penis. Picture: Virilizing adrenal hyperplasia in a newborn female baby, DHEA was converted to testosterone

Endocrine Activity of the Adrenal Cortex Hyper-secretion: Picture: micropenis in a newborn baby boy. micropenis is a result of hypopituitarism and lack of production of LH and therefore testosterone by the cells of Leydig

Other Thyroid Hormones Parafollicular cells Calcitonin

Parathyroid Hormones Principle Cells PTH

PTH and Calcitonin Interaction

Both Pancreatic Hormones interaction