Chapter 16 Endocrine System PDF

Chapter 16 -- Part A ==================== The Endocrine System Why This Matters ================ Understanding the endocrine system enables you to monitor and advise patients with diseases such as diabetes mellitus ----------------------------------------------------------------------------------...

Chapter 16 -- Part A ==================== The Endocrine System Why This Matters ================ Understanding the endocrine system enables you to monitor and advise patients with diseases such as diabetes mellitus --------------------------------------------------------------------------------------------------------------------- 16.1 Endocrine System Overview ============================== - **Endocrine system** acts with nervous system to coordinate and integrate activity of body cells ------------------------------------------------------------------------------------------------ - Influences metabolic activities via **hormones** transported in blood --------------------------------------------------------------------- - Responses slower but longer lasting than nervous system responses ----------------------------------------------------------------- - **Endocrinology**: study of hormones and endocrine organs --------------------------------------------------------- 16.1 Endocrine System Overview ============================== - Endocrine system controls and integrates: ----------------------------------------- ### Reproduction ### Growth and development ### Maintenance of electrolyte, water, and nutrient balance of blood ### Regulation of cellular metabolism and energy balance ### Mobilization of body defenses 16.1 Endocrine System Overview ============================== - Exocrine glands --------------- ### Produce nonhormonal substances (examples: sweat, saliva) ### Have ducts to carry secretion to membrane surface - **Endocrine glands** -------------------- ### Produce hormones ### Lack ducts 16.1 Endocrine System Overview ============================== - Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands ----------------------------------------------------------------------------- - Hypothalamus is **neuroendocrine** organ ---------------------------------------- - Some have exocrine and endocrine functions ------------------------------------------ ### Pancreas, gonads, placenta - Other tissues and organs that produce hormones ---------------------------------------------- ### Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart 16.1 Endocrine System Overview ============================== - Chemical messengers of endocrine system: ---------------------------------------- ### **Hormones**: long-distance chemical signals; travel in blood or lymph ### **Autocrines**: chemicals that exert effects on same cells that secrete them ### **Paracrines**: locally acting chemicals that affect cells other than those that secrete them ### Autocrines and paracrines are local chemical messengers; not considered part of endocrine system 16.2 Hormone Chemical Structure =============================== - Two main classes of hormones: ----------------------------- ### **Amino acid--based hormones** #### Amino acid derivatives, peptides, and proteins ### **Steroids** #### Synthesized from cholesterol #### Gonadal and adrenocortical hormones - A possible third class, **eicosanoids**, is considered a hormone by some scientists, but most classify it as a paracrine ------------------------------------------------------------------------------------------------------------------------ 16.3 Action of Hormones ======================= - Though hormones circulate systemically, only cells with receptors for that hormone are affected ----------------------------------------------------------------------------------------------- - **Target cells:** tissues with receptors for a specific hormone --------------------------------------------------------------- - Hormones alter target cell activity ----------------------------------- 16.3 Action of Hormones ======================= - Hormone action on target cells may be to: ----------------------------------------- ### Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels ### Stimulate synthesis of enzymes or other proteins ### Activate or deactivate enzymes ### Induce secretory activity ### Stimulate mitosis 16.3 Action of Hormones ======================= - Hormones act in one of two ways, depending on their chemical nature and receptor location ----------------------------------------------------------------------------------------- ### *Water-soluble hormones* (all amino acid--based hormones except thyroid hormone) #### Act on plasma membrane receptors #### Act via G protein second messengers #### Cannot enter cell ### *Lipid-soluble hormones* (steroid and thyroid hormones) #### Act on intracellular receptors that directly activate genes #### Can enter cell Plasma Membrane Receptors and Second-Messenger Systems ====================================================== - Amino acid--based hormones, except thyroid hormone, exert effects through **second-messenger systems** ------------------------------------------------------------------------------------------------------ - Two main second-messenger systems: ---------------------------------- ### **Cyclic AMP** ### **PIP~2~-calcium** Plasma Membrane Receptors and Second-Messenger Systems (cont.) ============================================================== - **Cyclic AMP (cAMP) signaling mechanism** ----------------------------------------- 1. ### Hormone (**first messenger**) binds to receptor 2. ### Receptor activates a **G protein** 3. ### G protein activates or inhibits effector enzyme **adenylate cyclase** 4. ### Adenylate cyclase then converts ATP to cAMP (**second messenger**) 5. ### cAMP activates protein *kinases* that *phosphorylate* (add a phosphate) other proteins Plasma Membrane Receptors and Second-Messenger Systems (cont.) ============================================================== - **Cyclic AMP (cAMP) signaling mechanism (cont.)** ------------------------------------------------- ### Phosphorylated proteins are then either activated or inactivated ### cAMP is rapidly degraded by enzyme **phosphodiesterase**, stopping cascade ### Cascades have huge amplification effect Plasma Membrane Receptors and Second-Messenger Systems (cont.) ============================================================== - **PIP~2~-calcium signaling mechanism** -------------------------------------- ### Hormone-activated G protein activates a different effector enzyme: **phospholipase C** ### Activated phospholipase C splits membrane protein, **PIP~2~**, into two second messengers: #### **Diacylglycerol** (**DAG**) activates protein kinases #### **Inositol trisphosphate** (**IP~3~**) causes Ca^2+^ release from intracellular storage sites Plasma Membrane Receptors and Second-Messenger Systems (cont.) ============================================================== - **PIP~2~-calcium signaling mechanism (cont.)** ---------------------------------------------- ### Calcium ions act as another second messenger #### Ca^2+^ alters enzyme activity and channels, or binds to regulatory protein **calmodulin** #### Calcium-bound calmodulin activates enzymes that amplify cellular response Plasma Membrane Receptors and Second-Messenger Systems (cont.) ============================================================== - **Other signaling mechanisms** ------------------------------ ### cGMP (cyclic guanosine monophosphate) is second messenger for selected hormones ### Other hormones work without second messenger system #### Example: insulin receptor is a *tyrosine kinase* enzyme that autophosphorylates upon insulin binding ##### Activated tyrosine kinases provide docking sites for *relay* proteins that trigger cell responses Intracellular Receptors and Direct Gene Activation ================================================== - Lipid-soluble steroid hormones and thyroid hormone can diffuse into target cells and bind with intracellular receptors ---------------------------------------------------------------------------------------------------------------------- - Receptor-hormone complex enters nucleus and binds to specific region of DNA --------------------------------------------------------------------------- - Helps initiate DNA transcription to produce mRNA ------------------------------------------------ - mRNA is then translated into specific protein --------------------------------------------- ### Proteins synthesized have various functions ### Examples: metabolic activities, structural purposes, or exported from cell 16.4 Hormone Release ==================== - Blood levels of hormones ------------------------ ### Controlled by **negative feedback systems** #### Increased hormone effects on target organs can inhibit further hormone release ### Levels vary only within narrow, desirable range ### Hormone release is triggered by: #### **Endocrine gland stimuli** #### **Nervous system modulation** Endocrine Gland Stimuli ======================= - Endocrine glands are stimulated to synthesize and release hormones in response to one of three stimuli: ------------------------------------------------------------------------------------------------------- ### **Humoral stimuli** ### **Neural stimuli** ### **Hormonal stimuli** Endocrine Gland Stimuli (cont.) =============================== - **Humoral stimuli** ------------------- ### Changing blood levels of ions and nutrients directly stimulate secretion of hormones ### Example: Ca^2+^ in blood #### Declining blood Ca^2+^ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone) #### PTH causes Ca^2+^ concentrations to rise, and stimulus is removed Endocrine Gland Stimuli (cont.) =============================== - **Neural stimuli** ------------------ ### Nerve fibers stimulate hormone release #### Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines Endocrine Gland Stimuli (cont.) =============================== - **Hormonal stimuli** -------------------- ### Hormones stimulate other endocrine organs to release their hormones #### Hypothalamic hormones stimulate release of most anterior pituitary hormones #### Anterior pituitary hormones stimulate targets to secrete still more hormones #### Hypothalamic--pituitary--target endocrine organ feedback loop ##### Hormones from final target organs inhibit release of anterior pituitary hormones Nervous System Modulation ========================= - Nervous system can make adjustments to hormone levels when needed ----------------------------------------------------------------- ### Can modify stimulation or inhibition of endocrine glands - Nervous system can override normal endocrine controls ----------------------------------------------------- ### Example: under severe stress, hypothalamus and sympathetic nervous system override insulin to allow blood glucose levels to increase #### Prepare body for "fight or flight" 16.5 Target Cell Specificity ============================ - Target cells must have specific receptors to which hormone binds ---------------------------------------------------------------- ### Example: ACTH receptors are found only on certain cells of adrenal cortex, but thyroxin receptors are found on nearly all cells of body - Target cell activation depends on three factors: ------------------------------------------------ 1. ### Blood levels of hormone 2. ### Relative number of receptors on/in target cell 3. ### *Affinity* (strength) of binding between receptor and hormone 16.5 Target Cell Specificity ============================ - Amount of hormone can influence number of receptors for that hormone -------------------------------------------------------------------- ### **Up-regulation**: target cells form more receptors in response to low hormone levels ### **Down-regulation**: target cells lose receptors in response to high hormone levels #### Desensitizes the target cells to prevent them from overreacting to persistently high levels of hormone Half-Life, Onset, and Duration of Hormone Activity ================================================== - Hormones circulate in blood either free or bound ------------------------------------------------ ### Steroids and thyroid hormone are attached to plasma proteins ### All others circulate without carriers - Concentration of circulating hormone reflects: ---------------------------------------------- 1. ### Rate of release 2. ### Speed at which it is inactivated and removed from body Half-Life, Onset, and Duration of Hormone Activity (cont.) ========================================================== - Hormones can be removed from blood by: -------------------------------------- ### Degrading enzymes or ### Kidneys or ### Liver #### **Half-life**: time required for level of hormone in blood level to decrease by half ##### Varies anywhere from fraction of a minute to a week, depending on hormone Half-Life, Onset, and Duration of Hormone Activity (cont.) ========================================================== - Hormones have different response times: --------------------------------------- ### Some responses are immediate ### Some, especially steroid, can take hours to days ### Some are inactive until they enter target cells - The duration of response is usually limited ------------------------------------------- ### Ranges from 10 seconds to several hours ### Effects may disappear rapidly as blood levels drop, but some may persist for hours at low blood levels Half-Life, Onset, and Duration of Hormone Activity (cont.) ========================================================== - Half-life, onset, and duration of hormone activity are dependent on whether the hormone is water or lipid soluble ----------------------------------------------------------------------------------------------------------------- Interaction of Hormones at Target Cells ======================================= - Multiple hormones may act on same target at same time ----------------------------------------------------- ### **Permissiveness**: one hormone cannot exert its effects without another hormone being present #### Example: reproductive hormones need thyroid hormone to have effect ### **Synergism**: more than one hormone produces same effects on target cell, causing amplification #### Example: glucagon and epinephrine both cause liver to release glucose Interaction of Hormones at Target Cells (cont.) =============================================== ### **Antagonism**: one or more hormones oppose(s) action of another hormone #### Example: insulin and glucagon 16.6 The Hypothalamus ===================== - **Hypothalamus** is connected to **pituitary** **gland** (**hypophysis**) via stalk called **infundibulum** ----------------------------------------------------------------------------------------------------------- - Pituitary secretes at least eight major hormones ------------------------------------------------ - It has two major lobes: ----------------------- ### **Posterior pituitary**: composed of neural tissue that secretes **neurohormones** #### Posterior lobe, along with infundibulum make up the **neurohypophysis** ### **Anterior pituitary**: (**adenohypophysis**) consists of glandular tissue Pituitary-Hypothalamic Relationships ==================================== - Posterior lobe is neural tissue derived from a downgrowth of brain ------------------------------------------------------------------ ### Maintains neural connection to hypothalamus via **hypothalamic-hypophyseal tract** #### Tract arises from neurons in **paraventricular** and **supraoptic nuclei** in hypothalamus #### Runs through infundibulum ### Secretes two neurohormones (oxytocin and ADH) #### Hormones are stored in axon terminals in posterior pituitary and are released into blood when neurons fire Pituitary-Hypothalamic Relationships (cont.) ============================================ - Anterior lobe is glandular tissue derived from an outpocketing of oral mucosa ----------------------------------------------------------------------------- ### Vascularly connected to hypothalamus via hypophyseal portal system consisting of: #### **Primary capillary plexus** #### **Hypophyseal portal veins** #### **Secondary capillary plexus** - Hypothalamus secretes **releasing and inhibiting hormones** to anterior pituitary to regulate hormone secretion --------------------------------------------------------------------------------------------------------------- Posterior Pituitary and Hypothalamic Hormones ============================================= - Posterior pituitary consists of axon terminals of neurons from hypothalamic neurons: ------------------------------------------------------------------------------------ ### Paraventricular neurons produce oxytocin ### Supraoptic neurons produce antidiuretic hormone (ADH) - **Oxytocin** and **ADH** ------------------------ ### Each composed of nine amino acids ### Almost identical but differ in two amino acids Posterior Pituitary and Hypothalamic Hormones (cont.) ===================================================== - **Oxytocin** ------------ ### Strong stimulant of uterine contractions released during childbirth ### Also acts as hormonal trigger for milk ejection ### Both are *positive feedback* mechanisms ### Acts as neurotransmitter in brain #### Uses PIP~2~-calcium second messenger system Posterior Pituitary and Hypothalamic Hormones (cont.) ===================================================== - **Antidiuretic hormone (ADH)** ------------------------------ ### Hypothalamus contains *osmoreceptors* that monitor solute concentrations ### If concentration too high, posterior pituitary triggered to secrete ADH ### Targets kidney tubules to reabsorb more water to inhibit or prevent urine formation ### Release also triggered by pain, low blood pressure, and drugs Posterior Pituitary and Hypothalamic Hormones (cont.) ===================================================== - **Antidiuretic hormone (ADH) (cont.)** -------------------------------------- ### Inhibited by alcohol, diuretics ### High concentrations cause vasoconstriction, so also called **vasopressin** Clinical -- Homeostatic Imbalance 16.1 ====================================== - **Diabetes insipidus** ---------------------- ### ADH deficiency due to damage to hypothalamus or posterior pituitary ### Must keep well hydrated - **Syndrome of inappropriate ADH secretion (SIADH)** --------------------------------------------------- ### Retention of fluid, headache, disorientation ### Fluid restriction; blood sodium level monitoring Anterior Pituitary Hormones =========================== - All six hormones are peptide hormones ------------------------------------- - All but growth hormone (GH) activate target cells via cAMP second-messenger system ---------------------------------------------------------------------------------- - All but two are **tropic hormones** (**tropins**) that regulate secretion of other hormones ------------------------------------------------------------------------------------------- ### **Growth** **hormone** (**GH**) ### **Thyroid**-stimulating **hormone** (**TSH**) (tropic) ### **Adrenocorticotropic** **hormone** (**ACTH**) (tropic) ### Follicle-**stimulating** **hormone** (**FSH**) (tropic) ### **Luteinizing** **hormone** (**LH**) (tropic) ### **Prolactin** (**PRL**) Anterior Pituitary Hormones (cont.) =================================== - **Growth hormone (GH)** ----------------------- ### Also called *somatotropin* as it is produced by **somatotropic cells** ### Has direct actions on metabolism and indirect growth-promoting actions ### **Direct actions on metabolism** #### *Glucose-sparing* actions decrease rate of cellular glucose uptake and metabolism (*anti-insulin effects*) #### Triggers liver to break down glycogen into glucose #### Increases blood levels of fatty acids for use as fuel and encourages cellular protein synthesis Anterior Pituitary Hormones (cont.) =================================== ### **Indirect actions on growth:** #### GH triggers liver, skeletal muscle, and bone to produce insulin-like growth factors (IGFs) #### IGFs then stimulate: ##### Cellular uptake of nutrients used to synthesize DNA and proteins needed for cell division ##### Formation of collagen and deposition of bone matrix #### GH stimulates most cells to enlarge and divide, but major targets are bone and skeletal muscle Anterior Pituitary Hormones (cont.) =================================== ### **Regulation of secretion** #### GH release or inhibition chiefly regulated by hypothalamic hormones on somatotropic cells ##### **Growth** hormone--**releasing** **hormone** (**GHRH**) stimulates GH release ###### Triggered by low blood GH or glucose, or high amino acid levels ##### **Growth** **hormone**--**inhibiting** **hormone** (**GHIH**) (somatostatin) inhibits release ###### Triggered by increase in GH and IGF levels #### Ghrelin (hunger hormone) also stimulates GH release Clinical -- Homeostatic Imbalance 16.2 ====================================== - Hypersecretion of GH is usually caused by anterior pituitary tumor ------------------------------------------------------------------ ### In children results in **gigantism** #### Can reach heights of 8 feet ### In adults results in **acromegaly** #### Overgrowth of hands, feet, and face - Hyposecretion of GH ------------------- ### In children results in **pituitary dwarfism** #### May reach height of only 4 feet ### In adults usually causes no problems Anterior Pituitary Hormones (cont.) =================================== - Thyroid-stimulating hormone --------------------------- ### Tropic hormone that is also called **thyrotropin** as it is produced by **thyrotropic cells** ### Stimulates normal development and secretory activity of thyroid ### Release triggered by **thyrotropin-releasing hormone** from hypothalamus ### Inhibited by rising blood levels of thyroid hormones that act on both pituitary and hypothalamus #### Also inhibited by GHIH Anterior Pituitary Hormones (cont.) =================================== - **Adrenocorticotropic hormone (ACTH)** -------------------------------------- ### Also called **corticotropin** as it is secreted by **corticotropic cells** #### Precursor to corticotropin is *pro-opiomelanocortin* ### ACTH stimulates adrenal cortex to release corticosteroids ### Regulation of ACTH release #### Triggered by hypothalamic **corticotropin-releasing hormone** (**CRH**) in daily rhythm ##### Highest levels in morning #### Internal and external factors that alter release of CRH include fever, hypoglycemia, and stressors Anterior Pituitary Hormones (cont.) =================================== - **Gonadotropins (FSH and LH)** ------------------------------ ### **Follicle**-**stimulating** **hormone** (**FSH**) and **luteinizing** **hormone** (**LH**) are secreted by **gonadotropic** **cells** of anterior pituitary ### FSH stimulates production of gametes (egg or sperm) ### LH promotes production of gonadal hormones #### In females, LH helps mature follicles of egg, triggers ovulation and release of estrogen and progesterone #### In males, LH stimulates production of testosterone Anterior Pituitary Hormones (cont.) =================================== - **Gonadotropins (FSH and LH) (cont.)** -------------------------------------- ### LH and FSH both are absent from blood in prepubertal boys and girls ### Regulation of gonadotropin release #### Triggered by **gonadotropin-releasing hormone** (**GnRH**) during and after puberty #### Suppressed by gonadal hormones (feedback) Anterior Pituitary Hormones (cont.) =================================== - **Prolactin (PRL)** ------------------- ### Secreted by **prolactin cells** of anterior pituitary ### Stimulates milk production in females; role in males not well understood ### Regulation primarily controlled by **prolactin-inhibiting hormone** (**PIH**), which is **dopamine** ### PIH prevents release of PRL until needed, with decreased levels leading to lactation Anterior Pituitary Hormones (cont.) =================================== - **Prolactin (PRL) (cont.)** --------------------------- ### Increased estrogen levels stimulate PRL #### Reason behind breast swelling and tenderness during menstrual cycle ### Blood levels rise toward end of pregnancy ### Suckling stimulates PRL release and promotes continued milk production Clinical -- Homeostatic Imbalance 16.3 ====================================== - Hypersecretion of prolactin is more common than hyposecretion ------------------------------------------------------------- ### Hyposecretion not a problem in anyone except women who choose to nurse - *Hyperprolactinemia* is the most frequent abnormality of anterior pituitary tumors ---------------------------------------------------------------------------------- - Clinical signs include inappropriate lactation, lack of menses, infertility in females, and impotence in males --------------------------------------------------------------------------------------------------------------