A&P II Chap 18 PDF - Lecture notes Chapter 18 PDF

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Endocrine System, hormones, glands, related disorders ...

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Anatomy & Physiology! Chapter 18 Notes! -Estrogens promote accumulation of adipose tissue in breasts/hips! -Testosterone helps build muscle mass and enlarge vocal cords! -Multitudes of hormones help maintain homeostasis on a daily basis ! -Hormone: molecule released in one part of the body but regulates the activity of cells in other parts of the body ! -Both neurotransmitters and hormones exert their effects by binding to receptors on or in their target cells ! -Norepinephrine: released as a NT by sympathetic post ganglionic neurons and as a hormone by chromaffin cells of the adrenal medullae ! -Responses of the endocrine system often are slower than responses of the nervous system ! $ -Most take several minutes ! -Certain parts of the nervous system stimulate or inhibit the release of hormones by the endocrine system ! Glands -Exocrine Glands: secrete their products into ducts that carry the secretions into body cavities, into the lumen of an organ, or to the outer surface of the body ! $ -Sudoriferous, sebaceous, mucous, digestive glands ! -Endocrine Glands: secrete their products (hormones) into the interstitial fluid surrounding the secretory cells rather than into ducts ! $ -Some of the most vascular tissues of the body ! $ -Pituitary, thyroid, parathyroid, adrenal, pineal ! Hormone Receptors -Hormones influence their target cells by chemically binding to specific protein receptors ! -Only the target cells for a given hormone have receptors that bind and recognize that hormone ! -Receptors are constantly being synthesized and broken down ! -Down-Regulation: if a hormone is present in excess, the number of target-cell receptors may decrease! $ -Makes a target cell less sensitive to a hormone ! -Up-Regulation: when a hormone is deficient, the number of receptors may increase ! $ -Makes a target cell more sensitive to a hormone ! -Circulating Hormones: pass from secretory cells that make them into interstitial fluid and then into the blood ! $ -May linger in the blood and exert their effects for a few minutes or hours ! $ -Inactivated by liver and excreted by kidneys ! -Local Hormones: act locally on neighboring cells or on the same cell that secreted them without entering the bloodstream ! $ -Paracrine: act on neighboring cells ! $ -Autocrine: act on the same cell ! $ -Interleukin-2 (IL2): helps activate other nearby immune cells (a paracrine effect)! $ $ -Acts as an autocrine by stimulating the same cell that released it to proliferate thus generating more helper T cells ! $ -Usually inactivated quickly ! Chemical Classes of Hormones -Lipid Soluble Hormones! $ -Steroid: derived from cholesterol !

$ $ -Each steroid hormone is unique due to the presence of different chemical groups attached at various sites on the four rings at the core of its structure ! $ -Thyroid: synthesized by attaching iodine to the amino acid tyrosine ! $ -Nitric Oxide (NO) Gas: both a hormone and NT ! -Water Soluble Hormones ! $ -Amine: synthesized by decarboxylating (removing a CO₂ molecule) certain amino acids ! $ $ -Catecholamines, histamine, 5H-T and melatonin ! $ -Peptides and Proteins: amino acid polymers ! $ $ -Smaller Peptide hormone consists of chains of 3-49 amino acids (ex. antidiuretic/oxytocin)! $ $ -Larger proteins include 50-200 AA (ex. growth hormone/insulin) ! $ -Glycoprotein Hormones: protein hormone with an attached carbohydrate group ! $ -Eicosanoid: derived from arachidonic acid, a 20 carbon fatty acid ! $ $ -Prostaglandins (PGs) and Leukotrienes (LTs)! $ $ $ -Important local hormones ! -Most water soluble hormone molecules circulate in the plasma in a “free” form (not attached to other molecules)! -Most lipid soluble hormone molecules are bound to transport proteins, synthesized in the liver ! $ -Make lipid soluble hormones temporarily water soluble ! -0.1-10% of the molecules of a lipid soluble hormone are not bound to a transport protein ! $ -This free fraction diffuses out of capillaries, binds to receptors, and triggers responses! $ -As free hormone molecules leave the blood and bind to their receptors, transport proteins release new ones to replenish the free fraction ! -Various target cells respond differently to the same hormone ! $ -Hormonal effects include:! $ $ -Synthesis of new molecules ! $ $ -Changing the permeability of the plasma membrane ! $ $ -Stimulating transport of a substance into or out of the target cells! $ $ -Altering the rate of specific metabolic reactions ! $ $ -Causing contraction of smooth/cardiac muscle ! -Receptors for lipid soluble hormones are located inside target cells ! -Receptors for water soluble hormones are part of the plasma membrane or target cells ! Actions of Lipid Soluble Hormones -Free lipid soluble hormone molecule diffuses from the blood into a cell! -Hormone binds to and activates receptors located within the cytosol or nucleus; receptorhormone complex then alters gene expression ! -New mRNA forms, leaves the nucleus, enters the cytosol and directs synthesis of a new protein ! -The new proteins alter the cells activity and cause the responses typical of that hormone ! Actions of Water Soluble Hormones -Cannot diffuse through lipid bilayer! -Bind to receptors that protrude from target cell surface ! $ -Integral membrane protein ! $ $ -First Messenger (Hormone): water soluble hormone binds to receptor at outer surface of membrane ! $ $ -Second Messenger: inside cell ! $ $ $ -Cyclic AMP! -Water soluble hormone (first messenger) diffuses from blood and binds to its receptor ! $ -This hormone-receptor complex activates a membrane protein called the G protein ! $ $ -G protein activates adenylyl cyclase !

-Adenylyl Cyclase converts ATP into cyclic AMP ! $ -This occurs in the cytosol ! -Cyclic AMP (second messenger) activates one or more protein kinases ! $ -Protein Kinase: an enzyme that phosphorylates other cellular proteins ! $ -Activated protein kinases phosphorylate one or more cellular proteins ! -Phosphorylated proteins cause reactions that produce physiological responses ! -Eventually, phosphodiesterase (enzyme) inactivates cAMP! -Other second messengers include calcium ions (Ca²⁺), cyclic guanosine monophosphate (cGMP), inositol triphosphate (IP₃), and diacylglycerol (DAG)! -Hormones that bind to plasma membrane receptors can induce their effects at very low concentrations because they initiate a cascade/chain reaction, each step of which amplifies the initial effect ! Hormone Interactions -Responsiveness of a target cell to a hormone depends on ! $ -Hormone’s concentration in the blood ! $ -Abundance of target cell’s hormone receptors ! $ -influences exerted by other hormones ! -Up-Regulation: more receptors ! -Down-Regulation: decreased number of receptors ! -Actions of some hormones on target cells require a simultaneous or recent exposure to a second hormone! $ -Said to have a permissive event ! $ $ -Sometimes the permissive hormone increases the number of receptors for the other hormone ! -Synergistic Effect: effect of two hormones acting together is greater than the sum of their indivudal effects ! -Antagonistic Effects: one hormone opposes the actions of another ! Control of Hormone Secretion ! -Release of hormones occurs in short bursts, with little or no secretion between bursts ! $ -When stimulated, an endocrine gland will release its hormone in more frequent bursts ! -Hormone secretion is regulated by:! $ -Signals from the nervous system ! $ -Chemical changes in the blood! $ -Other hormones ! -Most hormonal regulatory systems work via negative feedback; few operate via positive feedback! $ -Positive feedback: childbirth: oxytocin stimulates contractions, contractions stimulate more oxytocin release ! Hypothalamus and Pituitary Gland -Pituitary Gland (Hypophysis)! $ -Anterior (Adenohypophysis) ! $ $ -Epithelial tissue! $ $ -Pars Distalis: larger portion! $ $ -Pars Tuberalis: sheath surrounding the infundibulum ! $ -Posterior (Neurohypophysis) ! $ $ -Nervous Tissue ! $ $ -Pars Nervosa: larger bulbar portion ! $ -Pars Intermedia: atrophies during fetal development ! -Hypothalamus: master ! $ -Major link between endocrine and nervous systems !

$ -Cells in the hypothalamus synthesize at least 9 different hormones; pituitary gland secretes 7 ! -Anterior Pituitary ! $ -Somatotrophs: growth hormone (GH; HGH; Somatotropin) general body growth and metabolism ! $ -Thyrotrophs: thyroid-stimulating hormone (TSH or Thyrotropin) controls the secretions and other activity of thyroid gland ! $ -Gonadotrophs: secrete two gonadotropins, follice-stimulating hormone (FSH) and lutenizing hormone (LH)! $ -Lactotrophs: prolactin (PRL) initiates milk production ! $ -Corticotrophs: adrenocorticotropic hormone (ACTH or corticotropin) stimulates adrenal cortex to secrete glucocorticoids such as cortisol ! -Hypothalamus secretes 5 releasing hormones which stimulate secretion of anterior pituitary hormones: ! $ -Growth hormone releasing hormone (GHRH or somatocrinin) ! $ -Thyrotropin releasing hormone (TRH)! $ -Corticotropin releasing hormone (CRH) ! $ -Prolactin releasing hormone (PRH) ! $ -Gonadotropin releasing hormone (GnRH)! -Hypothalamus secretes 2 inhibiting hormones which suppress secretion of anterior pituitary hormones:$ ! $ -Growth hormone inhibiting hormone (GHIH)! $ -Prolactin inhibiting hormone (PIH)! Hypophyseal Portal System -In a portal system, blood flows from one capillary network into a portal vein and then into a second capillary network before returning to the heart ! -In this portal system, blood flows from capillaries in the hypothalamus into portal veins that carry blood to capillaries of the anterior pituitary ! -Superior hypophyseal arteries (branches of the internal carotid arteries) bring blood into the hypothalamus ! $ -At junction of median eminece and infundibulum, these arteries divide into a capillary network called the primary plexus of the hypophyseal portal system ! $ $ -From the primary plexus, blood drains into the hypophyseal portal veins that pass down the outside of the infundibulum ! -The hypophyseal portal veins divide again and form another capillary network called the secondary plexus of the hypophyseal portal system ! -Hypophyseal veins drain blood from the anterior pituitary ! Control of Anterior Pituitary Secretion -Neurosecretory cells (cluster of neurons located above optic chiasm) synthesize hypothalamic releasing and inhibiting hormones! -When these cells are excited, nerve impulses trigger exocytosis of the vesicles ! $ -The hypothalamic hormones then diffuse into the blood of the primary plexus of the hypophyseal portal system ! $ -Hormones are then transported by the blood through the hypophyseal portal veins and into the secondary plexus ! $ $ -This direct route permits hypothalamic hormones to act immediately on anterior pituitary cells ! $ $ -When stimulated, the anterior pituitary cells secrete hormones into the secondary plexus capillaries ! $ $ -From there, the hormones drain into the hypophyseal veins then travel to target tissues throughout the body !

-Tropic Hormones: anterior pituitary hormones that act on other endocrine glands ! -Release of anterior pituitary hormones is regulated not only by the hypothalamus but also by negative feedback ! $ -Ex. the secretory activity of three types of anterior pituitary cells (thyro, cortico, and gonadotrophs) decreases when blood levels of their target gland hormones rise ! Growth Hormone (GH) -Somatotrophs are the most numerous cells in the anterior pituitary ! -GH is the most plentiful anterior pituitary hormone ! -Insulin like growth factors (IGFs or somatomedians) are small protein hormones that indirectly promote the effects of GH ! -IGFs synthesized in the liver enter the blood as hormones that circulate to target cells throughout the body to cause growth ! -The effects of GH on metabolism are direct, meaning that GH interacts directly with target cells to cause specific metabolic reactions ! -Specific functions of IGFs and GH include: ! $ -Increase growth of bones and soft tissues:! $ $ -In bones, IGFs stimulate osteoblasts! $ $ -In soft tissues, IGFs cause cells to grow by increasing uptake of amino acids into cells and accelerating protein synthesis ! $ -Enhance lipolysis in adipose tissue ! $ $ -Results in increased use of the released fatty acids for ATP production ! $ -Decrease glucose uptake ! $ $ -Decreases use of glucose for ATP! $ $ -Spares glucose so that it is available to neurons for ATP production in times of glucose scarcity ! -Somatotrophs in the anterior pituitary release bursts of growth hormone every few hours, especially during sleep ! -Their secretory activity is controlled mainly by 2 hypothalamic hormones: ! $ -Growth hormone releasing hormone (GHRH)! $ -Growth hormone inhibiting hormone (GHIH)! -Factors that promote GHRH secretion ! $ -Hypoglycemia (low blood glucose)! $ -Decreased blood levels of fatty acids ! $ -Increased blood levels of amino acids ! $ -Deep sleep! $ -Increased activity of sympathetic NS ! $ -Other hormones (ex. estrogen, ghrelin)! -GHRH enters hypophyseal portal system and flows to AP where it stimulates somatotrophs to secrete GH! -GH acts directly on various cells ! $ -In liver, bone, skeletal muscle, and cartilage, GH is converted to IGFs! -Elevated levels of GH and IGFs inhibit release of GHRH and GH ! -Factors that promote GHIH secretion:! $ -Hyperglycemia (high blood glucose)! $ -Increased blood levels of fatty acids! $ -Decreased blood levels of amino acids ! $ -Obesity ! $ -Aging! $ -High blood levels of GH and IGFs! -In AP, GHIH prevents somatotrophs from secreting GH by interfering with the signaling pathway used by GHRH !

Thryoid Stimulating Hormone (TSH) -Stimulates synthesis and secretion of triiodothyronine (T₃) and thyroxine (T₄)! -Thyrotropin releasing hormone (TRH) from the hypothalamus controls TSH secretion ! -Release of TRH depends on blood levels of T₃ and T₄ -High levels inhibit secretion via negative feedback Follicle Stimulating Hormone (FSH) -Ovaries, testes -Stimulates follicular cells to secrete estrogens -Stimulates sperm production -Gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates FSH release -Release of GnRH and FSH is suppressed by estrogens and testosterones through negative feedback Lutenizing Hormone (LH) -Triggers ovulation -Stimulates formation of corpus luteum in ovary and the secretion of progesterone -Together, FSH and LH stimulate secretions of estrogens by ovarian cells -LH stimulates cells in testes to secrete testosterone Prolactin (PRL) -Together with other hormones, initiates and maintains milk production -By itself, PRL only has a weak effect -Ejection of milk depends on oxytocin released from posterior pituitary -Prolactin inhibiting hormone (PIH dopamine) -Just before each menstruation, PIH secretion diminishes and blood level of PRL rises, but not enough to stimulate milk production -During pregnancy, PRL level rises, stimulated by prolactin releasing hormone (PRH) from the hypothalamus -The sucking action of a nursing infant causes a reduction in hypothalamic secrete of PIH -Function of PRL in males is not known -Hypersecretion causes erectile dysfunction -In females, hypersecretion of PRL causes galactorrhea (inappropriate lactation) and amenorrhea (absence of menstrual cycles) Adrenocorticotropic Hormone (ACTH) -Controls production and secretion of cortisol and other glucocorticoids by the cortex of the adrenal glands -Corticotropin releasing hormone (CRH) from the hypothalamus stimulates secretion of ACTH by corticotrophs -Low blood glucose, physical trauma, and interleukin-1 stimulate release of ACTH -Glucocorticoids inhibit CRH and ACTH release via negative feedback Melanocyte-Stimulating Hormone (MSH) -Increases skin pigmentation in amphibians by stimulating the dispersion of melanin granules in melanocytes -Role in humans is unknown -Presence of MSH receptors in brain suggests it may influence brain activity

-There is little circulating MSH in humans -Continued administration of MSH for several days does produce a darkening of the skin -Excessive levels of corticotropin-releasing hormone (CRH) can stimulate MSH release -Dopamine inhibits MSH release Posterior Pituitary -Does not synthesize hormones, only stores and releases 2 hormones -Consists of axons and axon terminals of more than 10,000 hypothalamic nuerosecretory cells -Cell bodies located in paraventricular and supraoptic nuclei of hypothalamus -Their axons form the hypothalamic-hypophyseal tract -Tract begins hypothalamus and ends near blood capillaries in the posterior pituitary -Neuronal cell bodies synthesize oxytocin (OT) and antidiuretic hormone (ADH or vasopressin) -Axon terminals associated with specialized neuroglia called pituicytes -Pituicytes have a supporting role similar to that of astrocytes -Blood is supplied to the posterior pituitary by the inferior hypophyseal arteries -These arteries drain into the capillary plexus of the infundibular process, a capillary network that receives secreted OT and ADH -Hormones then pass into the hypophyseal veins for distribution to target cells in other tissues Control of Posterior Pituitary Secretion -Neurosecretory cells in paraventricular and supraoptic nuclei synthesize OT and ADH which are then packaged into vesicles -Vesicles move by fast axonal-transport along the hypothalamic-hypophyseal tract to axon terminals in posterior pituitary, where they are stored -Nerve impulses will trigger exocytosis and release of OT or ADH into bloodstream -Hormone then travels to its target tissues Oxytocin (OT) -Affects uterus and breasts during and after delivery -Stretching of the cervix stimulates release of OT which enhances contraction of smooth muscle cells in uterin wall -Stimulates milk ejection -Function in males and in non-pregnant females is not clear Antidiuretic Hormone -Decreases urine output -Causes kidneys to return more water to the blood -In the absence of ADH, urine output increases more than tenfold -Alcohol inhibits secretion of ADH which is why drinking alcohol causes infrequent urination -ADH decreases the water lost through sweating and causes constriction of arterioles, which increases blood pressure -Two major stimuli -Rise in blood osmolarity -Decrease in blood volume -Osmoreceptors, neurons in hypothalamus that monitor changes in blood osmolarity, detect high blood osmolarity

-Decreased blood volume is detected by volume receptors in the atria and by baroreceptors in the walls of certain blood vessels -When stimulated, these receptors synthesize and release ADH into bloodstream -Blood carries ADH to two target tissues: -Kidneys -Smooth muscle in blood vessel walls -Kidneys respond by retaining more water which decreases urine output -Smooth muscle in walls of arterioles contract in response to high levels of ADH which constricts the lumen of these blood vessels and increases blood pressure Thyroid Gland -Just inferior to larynx -Right and left lateral lobes on either side of trachea connected by an isthmus -About 50% of thyroid glands have a small third lobe, pyramidal lobe, extending superiorly from isthmus -Thyroid Follicles: microscopic spherical sacs that make up most of the gland -The wall of each follicle consists of follicular cells -A basement membrane surrounds each follicle -Follicular cells produce T₃ and T₄ -Parafollicular cells (C cells) lie in between follicles -They produce calcitonin (CT) which helps regulate calcium homeostasis Formation, Storage, and Release of Thyroid Hormones -Thyroid is the only endocrine gland that stores its secretory product in large quantities -Synthesis and secretion of T₃ and T₄ occur as follows: -Iodide trapping: follicular cells trap iodide ions (I⁻) by actively transporting them from the blood into the cytosol -Synthesis of Thyroglobulin: while follicular cells are trapping I⁻, they are also synthesizing thyroglobulin (TGB) -Secretory vesicles undergo exocytosis which releases TGB into the lumen of the follicle -Oxidation of Iodide: negatively charged iodide ions cannot bind to tyrosine until they undergo oxidation (removal of electrons) to iodine (I⁻ → I°) -As the iodide ions are being oxidized, they pass through the membrane into the lumen of the follicle -Iodination of Tyrosine: iodine atoms react with tyrosines that are a part of thyroglobulin molecules -Binding creates T₁ and T₂! $ $ -C...