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The Endocrine System Interacts with nervous system to coordinate and integrate activity of body cells Nervous System v. Endocrine System Control Nervous System Regulation by electrochemical impulses (electrical signals & neurotransmitters) Neurons deliver impulses to muscles & glands Rapid response Short duration Endocrine System Regulation by chemical messengers Hormones: long distance chemical signals travel in blood & lymph Hormones released into blood & transported to all cells Lag time (sec. to days) Prolonged response Endocrine System Controls growth & reproduction Mobilizes body defenses Maintains blood electrolytes, water & nutrient balance Maintains cellular metabolism Maintains energy balance Endocrine organs scattered about the body Two kinds of glands Exocrine – gland that secretes its product into an area of the body via ducts Nonhormonal Endocrine – gland that secretes its product into the blood without the use of ducts Produces hormones Local-acting molecules – i.e prostaglandin effect on smooth muscle cells Exocrine Glands Substances are routed to membrane surface through ducts – not systemically distributed Unicellular Goblet cells secrete mucus to lubricate internal surfaces. Found in epithelium of respiratory, digestive, urinary and reproductive systems Multicellular Sweat glands (secrete sweat), mammary glands (milk), sebaceous glands (sebum), salivary glands (saliva), pancreas (digestive enzymes), prostate gland (seminal fluid) Endocrine glands Produce hormones which are released into the blood that is passing through the gland Examples: Pineal gland Pituitary gland Thyroid gland Parathyroid gland Thymus gland Adrenal gland Mixed-Functioning Glands Pancreas Gonads Secretes digestive juices into pancreatic duct to small intestine (exocrine) Secretes insulin & glucagons into blood from Islets of Langerhans cells to regulate blood glucose levels (endocrine) Ovaries and testes produce steroid sex hormones Seminal vesicles produce seminal fluid Hypothalamus Neuroendocrine organ – regulates body homeostasis (neural) and acts on pituitary (endocrine) Other organs containing hormoneproducing cells Stomach – Gastrin, serotonin Small intestine- intestinal gastrin, secretin, cholecystokinin Kidney - Erythropoietin Skin- Cholecalciferol Heart- atrial natriuretic peptide Adipose tissue – leptin, resistin Hormones - Chemistry Hormones are either steroids, polypeptides, glycoproteins, or derivatives of amino acids Most hormones are amino acid based Simple amino acid derivatives – amines & thyroxine Peptides – short chains of amino acids Proteins – long polymers of amino acids Of major endocrine organs, gonadal & adrenocortical hormones are steroids Steroids are synthesized from cholesterol Mechanism of Hormone Action Alters plasma membrane permeability and/or membrane potential by opening or closing ion channels Stimulates production of regulatory molecules within cell Activates or deactivates enzymes Induces secretions Stimulates mitosis Mechanisms of Hormone Communication Second-Messenger Systems Amino acid-based hormones cannot penetrate cell plasma membrane Hormone binds to plasma membrane receptor which generates second messengers Examples Cyclic AMP PIP-calcium Cyclic AMP 3’5’-cyclic adenosine monophosphate Hormone (1st messenger) binds to plasma membrane receptor activating the signal transducer, G protein (light switch) G protein activates an effector enzyme, adenylate cyclase (GTP) GTP generates cAMP (2nd messenger) cAMP triggers cascade of chemical reactions within the cell (amplification effect) Cyclic AMP Chemical reactions set in motion by cAMP depend on Type of target cell Target cell is a cell that has proper receptors to react with a specific hormone Enzymes in the target cell Which hormone is 1st messenger cAMP action persists briefly, therefore no extracellular controls are necessary to stop activity Direct Gene Activation Steroid hormones (and thyroid hormone) can diffuse into target cells (lipid soluble) Steroid hormones bind to receptor and hormone-receptor enters nucleus and binds to DNA-associated receptor protein Thyroid receptors are on the DNA This “turns on” a gene → transcription of DNA → produce mRNA → translation → protein molecules (enzymes) → metabolic processes Interaction of Hormones at Target Cells Permissive effect: enhancement of a target organ’s responsiveness to a hormone from prior exposure to a different hormone Synergistic effect: effect of two or more hormones acting on an organ Antagonistic effect: occurs when the effect of one hormone opposes the effect of another on a target organ Interaction of Hormones at Target Cells Permissive effect Synergistic effect Thyroid hormone is necessary for normal reproductive system development Glucagon (pancreas) and epinephrine cause liver to release glucose to the blood efficiently Antagonistic effect Insulin (lowers blood sugar) is antagonized by action of glucagon (raises blood sugar) Control of Hormone Release Synthesis and release of most hormones are regulated by a negative feedback system Hormone secretion triggered by stimuli Hormone levels rise Target organ effects are produced Further hormone release inhibited As a result, concentration of hormones in blood varies within narrow range Control of Hormone Release Endocrine glands are stimulated by 3 types of stimuli Humoral Stimuli Response to changing levels of ions and nutrients Neural Stimuli Response to nerve fiber stimuli Ca2+ levels monitored by parathyroid (PTH) Release of norepinephrine & epinephrine by adrenal medulla during stress Hormonal Stimuli Response to other hormones Hypothalamic-pituitary-target feedback loop Pituitary Gland (Hypophysis) Located in the hypophyseal fossa of the sella turcica of the sphenoid bone Attached to the base of the brain underneath hypothalamus Composed of two separate lobes “pea on a stalk” Stalk, infundibulum, connects the gland to the hypothalamus Anterior lobe composed of glandular tissue which produces hormones and releases them into blood Posterior lobe composed of neurological tissue which releases neurohomones from hypothalamus Pituitary Gland Anterior lobe is called adenohypophysis and is referred to as master endocrine gland Now known to be controlled by hypothalamus Produces 6 hormones (proteins) Growth hormone (GH) Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Gonadotropins Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL) All affect target cells via cyclic AMP Pituitary Gland Posterior pituitary is called the neurohypophysis and is made up of axons of hypothalamic neurons Produces 2 hormones Oxytocin Antidiuretic hormone (ADH) Both use PIP-calcium second-messenger mechanism Pituitary Gland Hormones Growth Hormone (GH) Stimulates growth in all organs Promotes fat mobilization Inhibits blood sugar utilization Secretion of GH regulated by Growth hormone-releasing hormone (GHRH) opposed by the Growth hormoneinhibiting hormone (GHIH) Gigantism caused by hypersecretion in children Acromegaly occurs when hypersecretion occurs after epiphyseal plates have closed Pituitary dwarfism is caused by hyposecretion Pituitary Gland Hormones Thyroid-stimulating hormone (TSH) Stimulates normal development of thyroid Release is triggered by thyrotropin-releasing hormone (TRH) Rising blood levels of thyroid hormones acts on pituitary and hypothalamus to inhibit TSH In response, hypothalamus releases GHIH which helps block TSH Hyposecretion: Cretinism and myxedema Hypersecretion: Graves disease Pituitary Gland Hormones Adrenocorticotropic hormone (ACTH) Secreted by anterior pituitary lobe Stimulates adrenal cortex to release corticosteroid hormones that help body resist stressors Release triggered by corticotropic-releasing hormone (CRH) Rising levels of glucocorticoids block CRH and thus ACTH release Hypersecretion: Cushing’s disease Pituitary Gland Hormones Follicle-stimulating hormone (FSH) and Luteinizing hornmone (LH) Regulate function of the gonads Stimulate gamete production Promotes production of gonadal hormones LH works with FSH to cause egg maturation (ovarian follicle) LH triggers ovulation LH stimulates production of testosterone in males Hyposecretion: failure of sexual maturation Pituitary Gland Hormones Prolactin (PRL) Stimulates milk production in breasts Controlled by hypothalamic hormones Oxytocin Made by hypothalamic neurons and stored in posterior pituitary Strong stimulant of uterine contraction Stimulated by stretching of uterus and cervix Pituitary Gland Hormones Antidiuretic hormone (ADH) (vasopressin) Made by hypothalamic neurons and stored in posterior pituitary Diuresis is urine production: an antidiuretic inhibits urine formation Prevents wide swings in water balance Hypothalamic neurons monitor solute concentration of blood: when too concentrated, ADH released Targets kidney tubules to reabsorb more water from urine thus lowering urine volume Alcohol inhibits ADH thus causing copious urine output with resulting dry mouth and dehydration Diuretics antagonize ADH (manage hypertension, edema) Thyroid Gland Thyroid Hormone (TH) Thyroxine (T4) (4 bound iodine atoms) and triiodothyronine (T3) (3 iodine atoms) Except for adult brain, spleen, testes, uterus, and thyroid, TH affects every cell of body Stimulates protein synthesis Promotes maturation of nervous system Increases rate at which energy is used by body Thyroid-stimulating hormone (TSH) stimulates thyroid to produce thyroxine Hypothyroidism in adults – myxedema; in children –cretinism Goiter caused by lack of iodine Hyperthyroid – Graves disease (autoimmune disease?) Thyroid and Parathyroid Glands Calcitonin Produced by the thyroid Promotes decrease in blood calcium Direct antagonist of parathyroid hormone Parathyroid hormone (PTH) Secreted by parathyroid glands Helps increase calcium blood levels Affects the bones, kidneys and intestines Adrenal Glands Steroid hormones (corticosteroids) are synthesized from cholesterol by adrenal cortex Not stored in cells, so rate of release depends on rate of synthesis Mineralocorticoids (aldosterone) – act on the kidneys to regulate sodium and potassium balance Hypersecretion – aldosteronism Hyposecretion – Addison’s disease Adrenal Glands Aldosteronism Hypertension and edema due to excessive sodium ion and water retention Accelerated excretion potassium ions, which can lead to unresponsive neurons Addison’s disease Hyposecretory disorder of adrenal cortex Deficits in mineralocorticoids and glucocorticoids Severe dehydration and hypotension Adrenal Glands Steroid hormones (cont.) Glucocorticoids (cortisol) – regulate metabolism of blood sugar and other organic compounds, essential to life Modify gene activity Help respond to stressors Cortisol release promoted by ACTH Rising cortisol levels feed back to act on hypothalamus and anterior pituitary, preventing CRH release and shutting off ACTH and cortisol Adrenal Glands Stress response Stress results in rise in blood levels of glucose, fatty acids, amino acids caused by cortisol Cortisol provokes formation of glucose from fats & proteins Cortisol enhances epinephrine’s vasoconstrictive effects with rise of blood pressure Anti-inflammatory and anti-immune effects are associated with cortisol excess Cushing’s disease- may be caused by ACTHreleasing pituitary tumor, adrenal cortex tumor, or other malignancy Adrenal Glands Sex hormones (Gonadocorticoids) Androgens (weak male sex hormone) Estradiol (estrogen) Small amounts compared to those produced in sex organs Contribute to onset of puberty Gonads Produce steroid sex hormones Estrogens Progesterone Stimulates female secondary sex characteristics, stimulates maturation, help stimulate mammary gland development Helps maintain endometrium during pregnancy, increases uterine sensitivity to oxytocin, suppresses gonadotropin secretion Testosterone Stimulates development of male genitalia and secondary sex characteristics Pancreas Located behind stomach in abdomen Islets of Langerhans produce hormones Alpha (α) cells synthesize glucagon Glucagon is hyperglycemic; its target is the liver; increases blood glucose levels Beta (β) cells synthesize insulin Insulin is hypoglycemic; lowers blood sugar levels; inhibits breakdown of gylcogen Pancreas Diabetes mellitus (DM) Results from hyposecretion or hyperactivity of insulin Blood sugar levels remain high after a meal High hyperglycemia triggers hypoglycemic response and sugar levels go higher High sugar levels begin to be lost in urine Fats are mobilized: high fatty acid (and ketones) levels result; lowers pH Nervous systems initiates rapid breathing to raise pH Ketoacidosis can lead to coma and death if untreated Pancreas Diabetes mellitus (DM) Hyperinsulinism – excessive insulin secretion Results in low blood sugar levels (hypoglycemia) Triggers hyperglycemic hormones which cause anxiety, nervousness, tremors, weakness Insufficient delivery of glucose to brain cause disorientation and can lead to unconsciousness and death Treated by ingesting sugar Pineal Gland and Thymus Pineal Gland Hangs from the roof of the third ventricle in the diencephalon Endocrine function still mysterious Melatonin is produced (derived from serotonin) and peak levels cause drowsiness Related to day/night cycles (activated by light) helps control your circadian (or biological) rhythm and regulate certain reproductive hormones. Thymus Located in thorax, appears to be essential for development of immune response