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Endocrine System Chapter 11
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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I. Endocrine Glands and Hormones
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Endocrine Glands Ductless Secrete hormones into the blood
Hormones are carried to target cells having receptors for those hormones. Many organs secrete hormones other than those discussed in this chapter such as the heart, liver, kidneys, and adipose tissue. Neurohormones are secreted by specialized cells of the hypothalamus Hormones help regulate body metabolism, growth, and reproduction
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Major Endocrine Glands
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pineal gland Pituitary gland Hypothalamus Thyroid gland Adrenal gland Pancreas Pancreatic islet (of Langerhans) Ovary Testis (a) (b) b: © Ed Reschke
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Partial Listing of Endocrine Glands
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Chemical Classification of Hormones
Amines, derived from tyrosine and tryptophan Examples: hormones from the adrenal medulla, thyroid, and pineal glands Polypeptides and proteins Examples: antidiuretic hormone, insulin, and growth hormone
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Chemical Classification of Hormones
Glycoproteins are long polypeptides bound to a carbohydrate. Examples: follicle-stimulating and luteinizing hormones Steroids are lipids derived from cholesterol Examples: testosterone, estradiol, progesterone, cortisol Secreted by adrenal cortex and gonads
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Polypeptide & Glycoprotein Hormones
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Biosynthetic Pathway for Steroid Hormones
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interstitial (Leydig) cells C D Spermatic cord A B HO O OH Cholesterol Testis Seminiferous tubules CH3 CH3 C O O O O C Androstenedione Testosterone Secreted by Leydig cells of testes In testes In ovaries HO O OH Pregnenolone Progesterone Secreted by corpus luteum of ovaries CH2OH HO Estradiol-17β Ovary In adrenals C O HO OH Secreted by follicles of ovaries Follicles in ovary Corpus luteum O Ovary Cortisol (hydrocortisone) Secreted by adrenal cortex Adrenal cortex
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Hormone Classifications by action
Polar hormones: water soluble Cannot pass through plasma membranes Must be injected if used as a drug Includes polypeptides, glycoproteins, catecholamines, norepinephrine, and epinephrine Nonpolar: insoluble in water Often called lipophilic hormones Can enter target cells directly Include steroids, thyroid hormone, and melatonin Can be taken orally in pill form
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Prohormones and Prehormones
Prohormones are inactive hormones that must be cut and spliced together to be active. Example: proinsulin insulin Prehormones are inactive prohormones that must be modified within their target cells.
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Prohormones and Prehormones
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Common Aspects of Neural & Endocrine Regulation
Hormones and neurotransmitters both interact with specific receptors. Binding to a receptor causes a change within the cell. There are mechanisms to turn off target cell activity; the signal is either removed or inactivated. Neurotransmitters and hormones have many similarities Some hormones can also be neurotransmitters in the CNS
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Hormone Interactions A target cell is usually responsive to several different hormones. Hormones may be antagonistic, synergistic, or permissive. How a cell responds depends on the amount of hormone and the combination of all hormones.
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Hormone Interactions Synergistic Effects
Occur when two or more hormones work together to produce a particular effect Effects may be additive, as when epinephrine and norepinephrine each affect the heart in the same way. Effects may be complementary, as when each hormone contributes a different piece of an overall outcome. For example, producing milk requires estrogen, prolactin, and oxytocin.
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Hormone Interactions Permissive Effects
Occur when one hormone makes the target cell more responsive to a second hormone Exposure to estrogen makes the uterus more responsive to progesterone. Increased secretion of PTH makes the intestines more responsive to Vit D3 in calcium absorption
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Hormone Interactions Antagonistic Effects
Occur when hormones work in opposite directions. Insulin and glucagon both affect blood glucose concentration. Insulin stimulates glucose uptake to be stored as fat Glucagon stimulates glycogen breakdown to produce glucose
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Effects of hormone concentrations on tissue response
Hormone half-life The time required for the plasma concentration of a given amount of hormone to be reduced by half The half-life of hormones circulating in the blood ranges from minutes to hours to days. Most hormones are removed from the blood by the liver and converted to less active products
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Effects of hormone concentrations on tissue response
Tissues only respond when hormone concentrations are at a certain “normal” or physiological level. At higher pharmacological concentrations (when taken as drugs), effects may be different from normal. High concentrations may result in binding to receptors of related hormones. This can result in widespread side effects.
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Effects of hormone concentrations on tissue response
Priming Effects / Upregulation Some target cells respond to a particular hormone by increasing the number of receptors it has for that hormone. This makes it more sensitive to subsequent hormone release and have a greater response
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Effects of hormone concentrations on tissue response
Desensitization and Downregulation Prolonged exposure to high concentrations of hormone may result in a decreased number of receptors for that hormone. Occurs in adipose cells in response to high concentrations of insulin To avoid desensitization, many hormones are released in spurts, called pulsatile secretion.
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II. Mechanisms of Hormone Action
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Introduction Hormones bind to receptors on or in target cells.
Binding is highly specific. Hormones bind to receptors with a high affinity. Hormones bind to receptors with a low capacity; saturating the receptors with hormone molecules Lipophilic hormone receptors are in the cytoplasm or nucleus Water-soluble hormone receptors are on the outer surface of the plasma membrane
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Hormones That Bind to Nuclear Receptors
Lipophilic steroid hormones and thyroid hormone: Hormone travel to target cells attached to carrier proteins At the target cell, dissociate from the carrier protein and diffuse across the plasma membrane Once the hormone is inside the cell, it binds to receptors called nuclear hormone receptors because they activate genetic transcription
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Hormones That Bind to Nuclear Receptors
These hormone receptors serve as transcription factors. They are activated by the binding of the hormone The effect of these hormones is therefore to produce new proteins, usually enzymes that change metabolism inside the cell.
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Nuclear Hormone Receptors
Two regions on the receptor: Ligand-binding domain for the hormone DNA-binding domain for DNA Binding of the hormone activates the DNA-binding domain, and it binds to a hormone response element on the DNA which is a short DNA span adjacent to the gene that will be transcribed Modern science has identified many “orphan” receptors without a known ligand. Two main families – steroid family and thyroid family (thyroid hormone, Vit D, retinoic acid)
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Mechanism of steroid hormone action
Nongenomic action May occur in the cytoplasm and involve second-messenger systems May cause effects in seconds to minutes, much faster than expected
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Genomic action Classical mechanism – stimulates genetic transcription
Required at least 30 minutes to work Better established and understood mechanism Receptors are in the cytoplasm, though some may be in the nucleus Once the hormone binds to the receptor, the complex translocates to the nucleus Hormone-receptor complex binds to the specific hormone-response element of DNA
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Genomic action Hormone response elements have two “half-sites” which means that two ligand-bound receptors must bind. Called dimerization; this forms a homodimer since both complexes are the same The activated nuclear hormone receptor now stimulates transcription
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Mechanism of Steroid Hormone Action
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cytoplasm Nucleus DNA Figure 11.4 The mechanism of steroid hormone action 3 4 H mRNA Translocation 2 mRNA Carrier protein H H 5 1 Protein synthesis Receptor protein 6 Steroid hormone response H H Blood Target cell
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Receptors for Steroid Hormones
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Steroid hormone H Receptor protein for steroid hormone Ligand-binding domain DNA-binding domain Half-sites (a) DNA Hormone- response element Target gene Dimerization of receptor Steroid hormone H Steroid hormone DNA Genetic transcription (b) mRNA
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Coactivators and Corepressors
Molecules are needed in addition to the steroid hormone. They bind to the nuclear receptor proteins at specific regions. This changes the effect of a given hormone in different cells; may activate or suppress transcription factors
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Changes in receptor protein structure once the ligand binds
Removal of heat shock proteins that prevent the receptor from binding to DNA Recruitment of coactivator proteins while corepressor proteins are prevented from the binding site Coactivator proteins modify the chromatin to facilitate DNA transcription of mRNA
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Thyroid Hormone Action
Thyroxine (T4) travels to target cells bound to thyroxine-binding globulin (TBG). Some T3 is also released, but is not bonded to a carrier; “free iodine” Inside the target cell, T4 is converted to T3. Receptor proteins are located inside the nucleus bound to DNA.
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Thyroid Hormone Action
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cytoplasm Nucleus DNA 4 Receptor protein 5 T3 mRNA T3 mRNA Carrier protein (TBG) 3 T4 T3 6 Protein synthesis Binding protein 1 T3 7 2 Thyroid hormone response T4 T4 Blood Target cell
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Thyroid Hormone Action
The hormone response element on the DNA has two half-sites, one for a T3 receptor and one for a 9-cis-retinoic acid receptor (a Vit A derivative). Binding of these molecules forms a heterodimer because there are two different receptors The binding of T3 will cause corepressor proteins to be removed and coactivator proteins to be recruited. Vitamin D action in the cell is similar.
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Thyroid Hormone Action
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. RXR receptor (for 9-cis- retinoic acid) TR receptor (for triiodothyronine) Dimerization 9-cis-retinoic acid T3 Triiodothyronine DNA Hormone- response element Genetic transcription mRNA
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Hormones That Use 2nd Messengers
These hormones cannot cross the plasma membrane, so they bind to receptors on the cell surface. Activate an intracellular mediator called a second messenger There are three possible 2nd messenger mechanisms: Adenylate cyclase Phospholipase C Tyrosine kinase
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Adenylate Cyclase (cAMP) System
Used by epinephrine and norepinephrine Binds to a β-adrenergic receptor G-protein dissociates Activates adenylate cyclase Uses ATP to make cAMP cAMP activates protein kinase Protein kinase phosphorylates proteins in the target cell to alter cell metabolism cAMP inactivated by phosphodiesterase Some cell can use cGMP, which is similar in action
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Adenylate Cyclase (cAMP) System
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 Adenylate cyclase Plasma membrane Receptor protein Hormone α β α α γ 2 ATP G-proteins 3 cAMP + PPi Regulatory subunit Regulatory subunit 4 Protein kinase (inactive) cAMP Protein kinase (active) Phosphorylation of proteins Activation of specific enzymes 5 Inactivation of specific enzymes
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Phospholipase C System
Used by epinephrine in some cells Bind to α-adrenergic receptors G-protein dissociates Activates phospholipase C Produces IP3 and DAG Liberates Ca2+ from the endoplasmic reticulum Ca2+ activates calmodulin Activates protein kinases to modify enzymes
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Phospholipase C System
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Receptor protein 1 Phospholipase C Hormone Plasma membrane 2 DAG 3 G-proteins Ca2+ Ca2+ IP3 4 Ca2+ Cytoplasm Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Endoplasmic reticulum
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Two Systems for Epinephrine
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Liver cell 1 cAMP 2 Adenylate cyclase Beta-adrenergic effect of epinephrine Active protein kinase ATP Glycogen Ca2+ 5 Active protein kinase 3 Alpha-adrenergic effect of epinephrine Glucose 1-phosphate 4 Calmodulin Ca2+ 6 Glucose 6-phosphate Free glucose
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Tyrosine Kinase System
Insulin and growth factors uses this system The receptor is also the enzyme tyrosine kinase. The ligand-binding site is on the outside of the cell, and the enzyme faces the cytoplasm. The enzyme portion is activated via phosphorylation. The activated receptor phosphorylates insulin receptor substrate molecules. This activates a cascade of enzymatic activity.
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Tyrosine Kinase System
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Extracellular fluid Insulin Alpha Beta P P P P ADP ADP Cytoplasm ATP ATP ATP Insulin receptor ADP P 1. Binding of insulin to receptor proteins 2. Phosphorylation of receptor 3. Phosphorylation of signal molecules Tyrosine kinase now active Cascade of effects Glucose uptake and anabolic reactions (a) (b) (c)
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III. Pituitary Gland
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Introduction The pituitary gland is attached to the hypothalamus by the infundibulum Divided into an anterior lobe (adenohypophysis) and a posterior lobe (neurohypophysis) The anterior pituitary is glandular epithelium with two parts – pars distalis and pars tuberalis The posterior pituitary is nervous tissue and also called the pars nervosa
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Pituitary Gland Hypothalamus Optic chiasma Anterior lobe
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hypothalamus Optic chiasma Anterior lobe (adenohypophysis): Infundibulum Pars tuberalis Pars distalis Pars intermedia (fetus only) Posterior lobe (neurohypophysis)
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Posterior Pituitary Hormones
Stores and releases two hormones made in the hypothalamus: Antidiuretic hormone (ADH or Vasopressin) Made in supraoptic nucleus Promotes the reabsorption of water in the CT of the kidneys Oxytocin Made in paraventricular nucleus Stimulates contractions of uterus in childbirth and contraction of mammillary glands in the breast for lactation
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Hypothalamic Control of the Posterior Pituitary
ADH and oxytocin are produced by the supraoptic and paraventricular nuclei of the hypothalamus, respectively They are transported along axons of the hypothalamo-hypophyseal tract to the posterior pituitary where they are stored in axonal terminals. Release is controlled by neuroendocrine reflexes. ADH is stimulated by an increase in blood osmolality Oxytocin is stimulated by suckling
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Hypothalamic Control of the Posterior Pituitary
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Paraventricular nucleus ADH and oxytocin produced here Supraoptic nucleus Hypothalamus Optic chiasma Infundibulum Hypothalamo- hypophyseal tract Posterior pituitary Anterior pituitary ADH and oxytocin released
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Anterior Pituitary Hormones
Secreted by the anterior lobe Trophic hormones stimulate hormone secretion in other glands: Growth hormone (GH) Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) – in the male, it is interstitial cell stimulating hormone (ICSH) Prolactin (PRL)
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**Anterior Pituitary Hormones
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Anterior Pituitary Hormones
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Paraventricular nucleus Hypothalamus Supraoptic nucleus Median eminence Portal system Infundibulum Posterior pituitary Anterior pituitary TSH Prolactin Thyroid Mammary gland ACTH Adrenal cortex Growth hormone FSH Gonadotropins LH Adipose tissue Bone Muscle Ovary Testis
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Hypothalamic Control of the Anterior Pituitary
The anterior pituitary is controlled via releasing and inhibiting hormones transported through the hypophyseal portal system. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell body Axons to primary capillaries Median eminence Primary capillaries Portal venules Pituitary stalk Releasing hormones Posterior pituitary Secondary capillaries Anterior pituitary hormones Anterior pituitary
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Hypothalamic Control of Anterior Pituitary
Releasing and inhibiting hormones released from the hypothalamus Corticotropin-releasing hormone (CRH) Gonadotropin-releasing hormone (GRH) Prolactin-inhibiting hormone (PIH) (dopamine) Somatostatin Thyrotropin-releasing hormone (TRH) Growth hormone−releasing hormone (GHRH)
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**Hypothalamic Control of Anterior Pituitary
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Feedback Control of the Anterior Pituitary
The final product regulates secretion of pituitary hormones – negative feedback inhibition The relationship between the hypothalamus, anterior pituitary, and the target tissue is called an axis Inhibition can occur at the pituitary gland level to inhibit response to hypothalamic hormones. Inhibition can occur at the hypothalamus level to inhibit the secretion of releasing hormones.
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Feedback Control of the Anterior Pituitary
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. – Hypothalamus Sensor Integrating center Effector Thyrotropin- releasing hormone (TRH) Inhibits secretion of TRH – Anterior pituitary Inhibits responsiveness to TRH Thyroid- stimulating hormone (TSH) Growth of thyroid Thyroid Thyroxine
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Feedback Control of the Anterior Pituitary
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sensor Integrating center Effector – Hypothalamus Gonadotropin- releasing hormone (GnRH) Negative feedback – Anterior pituitary Negative feedback Gonadotropins (FSH and LH) Inhibits secretion of GnRH Inhibits responsiveness to GnRH Gonads Sex steroid hormones (estrogens and androgens)
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Higher Brain Controls Since the hypothalamus receives input from higher brain regions, emotions can alter hormone secretion. At least 26 brain regions and olfactory neurons send axons to the GnRH-producing neurons. Stressors increase CRH production as part of the pituitary-adrenal axis Circadian rhythms
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IV. Adrenal Glands
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Structure of the Adrenal Glands
Found atop the kidneys Consist of an outer adrenal cortex and an inner adrenal medulla that function as separate glands The adrenal medulla is neural tissue and secretes epinephrine and norepinephrine in response to sympathetic neural stimulation. The adrenal cortex is glandular epithelium and secretes steroid hormones in response to ACTH
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Adrenal Glands Adrenal gland Kidney Adrenal cortex Adrenal medulla
Conective tissue capsule Zona glomerulosa Adrenal cortex Zona fasciculata Zona reticularis Adrenal medulla Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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Functions of the Adrenal Cortex
Secretes hormones made from cholesterol; called corticoseroids or corticoids Three categories: Mineralocorticoids (ex. aldosterone) from the zona glomerulosa regulate Na+ and K+ balance. Glucocorticoids (ex. cortisol) from the zona fasciculata regulate glucose metabolism. Adrenal androgens (ex. DHEA) from the zona reticularis are weak sex hormones that supplement those made in the gonads.
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Functions of Cortisol (Hydrocortisone)
Stimulates protein degradation Stimulates gluconeogenesis and inhibits glucose utilization to raise blood glucose levels Stimulates lipolysis Exogenous glucocorticoids are used medically to suppress immune response and inhibit inflammation; can have many negative side effects
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Steroid Hormones of the Adrenal Cortex Dehydroepiandrosterone
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Zona glomerulosa Zona fasciculata and zona reticularis Cholesterol Cholesterol Pregnenolone Pregnenolone 17-Hydroxypregnenolone Dehydroepiandrosterone (DHEA) Progesterone Progesterone 17-Hydroxyprogesterone Androstenedione Deoxycorticosterone Deoxycorticosterone Deoxycortisol Other androgens Corticosterone Corticosterone Cortisol Aldosterone Mineralocorticoids Glucocorticoids Sex steroids
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Functions of the Adrenal Medulla
Chromaffin cells release epinephrine and norepinephrine Activated with sympathetic response Have effects similar to sympathetic innervation but lasting 10 times longer Increase cardiac output, respiratory rate, and mental alertness; dilate coronary blood vessels; elevate metabolic rates
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Stress and the Adrenal Gland
Stress increases secretion of ACTH, which results in increased glucocorticoid release. The stress hormones are glucocorticoids (cortisol), epinephrine, and CRH Called the general adaptation syndrome (GAS). Good for proper recovery after stress, such as an illness or trauma. Cortisol helps inhibit the immune system so it does not overrespond.
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Stages of GAS Alarm reaction – activates the adrenal glands
Stage of resistance – readjustments in response to chronic illness or degree of infections Stage of exhaustion – may lead to sickness or death if readjusment is inadequate GAS effects Stimulates growth of adrenal glands Atrophy of lymphatic tissue of spleen, lymph nodes, and thymus Formation of bleeding peptic ulcers
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Stress and the Adrenal Gland
Chronic stress leads to an increased risk of illness. Cortisol may act on higher brain regions, contributing to depression and anxiety and memory suppression. By stimulating the liver to release glucose, insulin receptors may become resistant, making it harder to treat people with diabetes.
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Activation of hypothalamo-pituitary-adrenal axis by nonspecific stress
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sensor Higher brain centers Nonspecific stress Integrating center Effector – Hypothalamus Negative feedback CRH – Anterior pituitary Cortisol Adrenal cortex ACTH
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V. Thyroid and Parathyroid Glands
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Thyroid Gland Structure
Located just below the larynx Has two lobes on either side of the trachea, connected by the isthmus Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid cartilage of larynx Cricoid cartilage of larynx Thyroid gland Trachea
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Microscopic Thyroid Gland Structure
Consists of large sacs called thyroid follicles, which are lined with simple cuboidal epithelium called follicular cells that produce thyroglobulin. Interior of the follicles are filled with a protein-rich fluid called colloid. Areas between the follicles are occupied by parafollicular cells that secrete calcitonin
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Microscopic Thyroid Gland Structure
Colloid-filled follicle Parafollicular cells (secrete calcitonin) Follicular cells (secrete thyroglobulin)
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Production & Action of Thyroid Hormone
Thyroglobulin is made by the follicular cells. Thyroid follicles actively accumulate iodide (I-) and secrete it into the colloid. The iodine is attached to tyrosines within the thyroglobulin molecule. One iodine produces monoiodotyrosine (MIT). Two iodines produce diiodotyrosine (DIT).
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Production & Action of Thyroid Hormone
Enzymes within the colloid attach MIT and DIT together: DIT + DIT = T4 (tetraiodothyronine or thyroxine) DIT + MIT = T3 (triiodothyronine) These are still bound to thyroglobulin while in colloid. They dissociate from thyroglobulin when the thyroid gland is stimulated by TSH. Secreted into the blood
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Production & Storage of Thyroid Hormone
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood plasma Thyroid follicle I– (Iodide in plasma) Thyroid uptake of iodide Oxidized iodide Monoiodotyrosine (MIT) Peroxidase I– + H2O2 Diiodotyrosine (DIT) Thyroglobulin MIT + DIT DIT + DIT Colloid Triiodothyronine (T4) Tetraiodothyronine (T4) Bound to thyroglobulin Endocytosis stimulated by TSH Plasma carrier protein T3 T4 Thyroid hormone secretion
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*Action of Thyroid Hormone
T3 is active form Stimulates protein synthesis Promotes maturation of the nervous system Increases rates of cellular respiration Elevates basal metabolic rate
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Calcitonin Made by the parafollicular cells
Inhibits resorption of calcium from bone and stimulates secretion of calcium in the kidneys (in the DCT) to lower blood calcium levels
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Diseases of the Thyroid
Iodine deficiency leads to overstimulation of the thyroid gland (no negative feedback on pituitary gland) and growth of a goiter. It also leads to hypothyroidism: low metabolic rates, weight gain and lethargy, poor adaptation to cold stress, and myxedema (accumulation of fluids in subcutaneous connective tissues). Grave’s Disease – hyperthyroidism Cretinism results from hypothyroidism during pregnancy to about 6 months after birth
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Comparing Hyperthyroidism & Hypothyroidism
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How Iodine Deficiency Causes a Goiter
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sensor Integrating center Effector Hypothalamus – TRH – Anterior pituitary Normal thyroid TSH Thyroid If iodine adequate If iodine inadequate Negative feedback Low T3 and T4 T3 and T4 Low negative feedback Anterior pituitary Excess TSH Thyroid Growth (goiter) Hypertrophy– produces goiter
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Endemic Goiter Caused by Low Iodine
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Parathyroid Glands Generally 4 glands located in the back of the thyroid gland Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pharynx Thyroid gland Parathyroid glands Esophagus Trachea
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Parathyroid Glands Secrete parathyroid hormone (PTH) Hormone actions:
Increase absorption of Ca2+ in intestines Increase resorption of Ca2+ from bones Increase reabsorption of Ca2+ from DCT of nephron Results in rise in blood calcium level Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Decreasing blood Ca2+ – Sensor Integrating center Effector Parathyroids Parathyroid hormone Kidneys Bone Reabsorption of Ca2+ Dissolution of CaPO4 crystals Negative feedback Increased blood Ca2+ Decreased urinary excretion of Ca2+
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VI. Pancreas and Other Endocrine Glands
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Pancreas The pancreas is both an endocrine and an exocrine gland.
Endocrine cells are located in pancreatic islets (islets of Langerhans). Alpha cells: glucagon Beta cells: insulin
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Pancreas Gallbladder Pancreatic islet (of Langerhans) Beta cell Celiac
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Gallbladder Pancreatic islet (of Langerhans) Beta cell Celiac artery Alpha cell Aorta Common bile duct Tail of pancreas Pancreatic duct Duodenum Body of pancreas
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Insulin Primary hormone regulating plasma glucose concentration.
Insulin is secreted by beta cells when blood glucose levels rise after a meal. Its purpose is to lower blood glucose levels to the “normal” range.
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Action of Insulin Insulin binds to receptors on target cells.
Vesicles with GLUT4 carrier proteins bind to membrane. Glucose diffuses through GLUT4 channels by facilitated diffusion Occurs in adipose tissue, skeletal muscle, and the liver. Indirectly stimulates the enzyme glycogen synthase in liver and skeletal muscles to promote sugar storage Stimulates adipose tissue to store fat
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Action of Insulin 1 Insulin Insulin receptor GLUT4 Glucose P
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 Insulin Insulin receptor GLUT4 Glucose P 4 Translocation 3 Signaling molecules 2 4 Translocation Vesicles 3
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Glucagon Antagonistic to insulin
Secreted by alpha cells when blood glucose levels are low Purpose is to raise blood glucose levels to a “normal” range
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Action of Glucagon Stimulates liver to hydrolyze glycogen into glucose and release it into the blood Stimulates gluconeogenesis, conversion of noncarbohydrates into glucose Stimulates lipolysis in adipose tissue so fat is released and used as a fuel source instead of glucose
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Glucose Homeostasis Sensor Integrating center Effector Blood
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sensor Integrating center Effector Blood Pancreatic islets Blood Pancreatic islets α cells Glucagon Glucose in plasma α cells Glucagon β cells Insulin Glucose in plasma β cells Insulin – – Cellular uptake of glucose Glucose in plasma Cellular uptake and utilization of glucose Glycogenolysis Glucose in plasma Gluconeogenesis (a) (b)
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Pineal Gland Located on roof of third ventricle in the brain
Secretes the hormone melatonin Regulated by the suprachiasmatic nucleus of the hypothalamus through sympathetic neurons Stimulates melatonin production when it gets dark Part of the regulation of circadian rhythms Requires melanopsin found in the ganglion cells of the retina Secretion related to puberty, jet lag, and seasonal affective disorder
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Secretion of Melatonin
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Melatonin H H H O CH3O C C N C CH3 N H H H Pineal gland Day Inhibition Sympathetic neurons Suprachiasmatic nucleus (the "biological clock") Night Stimulation Retinohypothalamic tract Superior cervical ganglion
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Other Endocrine Glands
Gastrointestinal tract: Several hormones are made in the stomach and small intestine to regulate digestive processes; includes gastrin, secretin, cholecystokinin Gonads: Produce testosterone, estrogen, and progesterone to regulate production of gametes and secondary sexual characteristics Placenta: produces human chorionic gonadotropin (hCG) and samatomammotropin to regulate pregnancy
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VII. Paracrine and Autocrine Regulation
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Autocrine vs. Paracrine Signals
Both are involved in short-range signaling between neighboring cells within an organ. Autocrine signals: The sender and receiver are the same cell type. Paracrine signals: The sender and receiver are different cell types/tissues.
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Examples of Autocrine Regulation
Many regulatory molecules are called cytokines or growth factors. Cytokines regulate cells of the immune system Grow factors promote growth and cell division Given specific names depending on where they are found and what they do — for example, lymphokines, neurotrophins Most control gene expression in the target cell.
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Autocrine and Paracrine Regulators
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Prostaglandins Made from arachidonic acid released from phospholipids in the plasma membrane using the enzyme cyclooxygenase (COX); part of the eicosanoid family Alternatively, the cell may make leukotrienes using the enzyme lipoxygenase Released from almost every cell, with a wide range of function
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Formation and Action of Prostaglandins
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phospholipids of plasma membrane Arachidonic acid COOH Lipoxygenase Cyclooxygenase PGG2 PGH2 Leukotrienes PGI2 PGE2 PGF2α TXA2 Inflammation Antiplatelet aggregation Smooth muscle relaxation Smoothmuscle contraction Platelet aggregation Bronchoconstriction; vasoconstriction; capillary permeability Vasodilation Vasodilation Vasoconstriction Vasoconstriction
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Examples of Prostaglandin Action
Immune system: promote inflammation, pain, and fever Reproductive system: aid ovulation Digestive system: inhibit secretion; stimulate propulsion and absorption Respiratory system: aid bronchoconstriction and dilation Circulation: affect vasoconstriction and dilation, blood clotting Urinary system: increase blood flow to the kidneys, which increases excretion of urine
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Inhibitors of Prostaglandin Synthesis
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs inhibit prostaglandin synthesis by inhibiting the enzyme cyclooxygenase (COX). Side effects include gastric bleeding, kidney problems, and less clotting Aspirin is the most common; also indomethacin, and ibuprofen
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Inhibitors of Prostaglandin Synthesis
COX-2 Inhibitors: Celebrex and Vioxx Cyclooxygenase comes in two forms: COX-1 is found in the stomach and kidneys. COX-2 is involved in inflammation. Newer drugs that inhibit COX-2 selectively avoid gastric and kidney-related side effects. Unfortunately, these drugs increase the chance of stroke and heart attack, so they have been pulled from the market.
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Inhibitors of Prostaglandin Synthesis
Acetaminophen inhibits a newly discovered COX-3 isozyme to reduce fever and pain but not inflammation Antileukotrienes inhibit 5-lipoxygenase; used to treat asthma (Singulair)
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