Chapter 11 The endocrine system Neurotransmitter from a nerve cell Nerve cell Nerve signals Neurotransmitter molecules Nerve cell / muscle cell / gland cell Hormone from an endocrine cell Hormones are chemical messengers that enter the blood, which carries them from their site of secretion to the cells upon which they act. The endocrine system consists of all those glands, called endocrine glands, that secrete hormones. Secretory vesicles Endocrine cell Hormone molecules Blood vessel Target cell Exocrine gland vs. Endocrine gland Hormone-secreting cells Comparison between nervous system and endocrine system Types of hormones (1) (1) Peptides and proteins (2) Amines (3) Steroids Thyroid hormones Types of hormones (2) Chemical structures of the amine hormones Thyroid hormones By thyroid gland Ps. Adrenal cortex make steroid hormones By adrenal medulla Catecholamines Phenyl-N-methyl transferase (PNMT) Norepinephrine (1X) Epinephrine (4X) By hypothalamus Typical synthesis and secretion of peptide hormones Most hormones @ ribosome @ Golgi @ rER Structures of representative steroid hormones and their structure relationship to cholesterol Adrenal cortex Gonads (testes, ovaries) 1,25-dihydroxyvitamin D (from the kidneys) Steroid synthesis cytochrome P450s The major five hormones secreted from the adrenal cortex Androgens (Testosterone-like hormones) DHEA (1) Organic metabolism Glucocorticoids (2) Responses to stress (3) Regulation of the immune system (1) Na+ and H O retension Mineralocorticoid 2 (2) K+ and H+ excretion in the urine IP3 Angiotensin II Section through and adrenal gland Corticosterone Masculinization (1) Excessive body & facial hairs (2) Muscle development (3) Deepend voice Gonadal production of steroids Only the ovaries have high concentration of the enzyme estrogens Categories of hormones A hormone’s concentration in the plasma depends upon (1) its rate of secretion by the endocrine glans (2) its rate of removal from the blood Human endocrine glands and some of their hormones (1) Human endocrine glands and some of their hormones (2) Possible fates and actions of a hormone following it secretion by an endocrine cell The ability of thyroid hormone to “permit” epinephrine-induced release of fatty acids from adipose tissue cells Permissiveness: hormone A must be present for the full strength of hormone B’s effect. By causing an increased number of epinephrine receptors (-adrenergic receptors) Input that act directly on endocrine gland cells to stimulate or inhibit hormone secretion Ex: paracrine Example of how the direct control of hormone secretion by the plasma concentration of a substance Pathways by which the nervous influences hormone secretion Types of endocrine disorders (1) Too little hormone: hyposecretion (2) Too much hormone: hypersecretion (3) Reduced responsiveness of the target cells to hormone (hyporesponsiveness) (4) Increased responsiveness of the target cells to hormone (hyperresponsiveness) Hyposecretion Primary hyposecretion: an endocrine gland may be secreting too little hormone because the gland cannot function normally. (1) Partial destruction of a gland; (2) An enzyme deficiency resulting in decreased synthesis of the hormone; (3) Dietary deficiency of iodine (thyroid hormones) Secondary hyposecretion: the endocrine gland is not damaged initially but is receiving too little of its tropic hormone. If tropic hormone : primary Dwarfish: If tropic hormone : secondary hyposecretion of growth hormone Treatment: to administer the missing hormone or a synthetic analog of the hormone. Hypersecretion Acromegaly: Primary hypersecretion: hypersecretion of growth hormone the gland is secreting too much of the hormone on it own. Secondary hypersecretion: excessive stimulation of the gland by its tropic hormone. If tropic hormone & target hormone : primary If tropic hormone & target hormone : secondary Treatment: surgery Radiation Drugs that inhibit a hormone’s synthesis Drugs that block the hormone’s action on its target cells Hyporesponsiveness & Hyperresponsiveness Hyporesponsiveness: the target cells do not respond normally to the hormone. (1) Deficiency of receptors-or abnormal receptors-for the hormone. (2) The receptors for a hormone may be normal but some event that occurs after hormone binds to receptors may be defective. (ex: cAMP) (3) Require metabolic activation by some other tissue after secretion. There may be a deficiency of the enzymes that catalyze the activation. (ex: testosterone →→→ dihydrotestosterone) Hyperresponsiveness: Thyroid hormone causes an up-regulation of certain receptors for epinephrine; therefore, hypersecretion of thyroid hormone causes a hyperresponsiveness to epinephrine. (increased heart rate with elevated levels of thyroid hormones) Type 2 diabetes Type 2 (non-insulin-dependent) is - caused by a reduced response to insulin. - associated with being overweight and underactive. - the cause of more than 90% of diabetes. Location of the hypothalamus and pituitary Brain Hypothalamus Posterior pituitary Anterior pituitary Bone Hormone of the posterior pituitary Hypothalamus Neurosecretory Hormone cell Posterior pituitary Anterior Blood pituitary vessel ADH: antidiuretic hormone Oxytocin ADH Vasopressin Uterine muscles Kidney Mammary glands tubules Hormone of the anterior pituitary Neurosecretory cell of hypothalamus releasing hormones inhibiting hormones Blood vessel Releasing hormones TSH: thyroid-stimulating hormone from hypothalamus ACTH: adrenocorticotropic hormone Endocrine cells of FSH: follicle-stimulating hormone the anterior pituitary LH: luteinizing hormone Pituitary hormones PRL: prolactin GH: Growth hormone TSH ACTH FSH Prolactin Growth Endorphins and (PRL) hormone Endophines LH (GH) Thyroid Adrenal Testes or Mammary Entire Pain cortex ovaries glands body receptors (in mammals) in the brain Neural and vascular connections between the hypothalamus and pituitary gland Hormone secretion by the anterior pituitary gland The effect of definitely established hypophysiotropic hormones Hypophysiotropic hormones = hypothalamic releasing or inhibiting hormones ? peptides catecholamine Targets and major functions of the six classical anterior pituitary gland hormone Growth hormone Thyroid-stimulating Adrenocorticotropic Gonadotropic hormones somatotropin hormone hormone gonadotropins thyrotropin corticotropin Follicle-stimulating Luteinizing hormones hormone T4 T3 -lipotropin →→ mobilize fats in the circulation -endrophin →→ pain-killing The hypothalamic-anterior pituitary gland system Typical sequential pattern by which a hypophysiotropic hormone controls the secretion of downstream hormones CRH-ACTH-cortisol sequence Stressful stimuli Nonstress inputs Short-loop and long-loop feedbacks Colloid in the bilobed thyroid gland Thyroxine (T4) deiodinases Protein-rich Triiodothyronine (T3) Receptors for thyroid hormones are present in the nuclei of most of the cells of the body, but have a much higher affinity for T3. Steps involved in T3 and T4 formation Iodide trapping Thyroid peroxidase DIT: diiodotyrosine MIT: monoiodotyrosine Thyroid peroxidase T3, T4 stimulate the activity of Na+/K+-ATPase (1) Stimulate carbohydrate absorption from the small intestine (2) Increase fatty acid release from adipocytes Provide energy to maintain metabolic rate at a high level (calorigenic action heat production) TRH-TSH-thyroid hormone sequence Permissive actions of thyroid hormones T3, T4 -adrenergic receptors Epinephrine & Norepinephrine mediated sympathetic nervous system activity Hypothyroidism Hypothyroidism: the plasma levels of T3 and T4 are chronically below normal. Most cases of hypothyroidism (95%) are primary defects resulting from damage to or loss of functional tissue or from inadequate iodine consumption. The signs and symptoms of hypothyroidism: (1) An increased sensitivity to cold (cold intolerance) and a tendency toward weight gain. (2) In severe, certain hydrophilic polymers called glycosaminoglycans accumulate in the interstitial space in scattered regions of the body. Myxedema Goiter at an advanced stage If a thyroid cell is exposed to higher TSH levels than normal, it will undergo hypertrophy (increase in size). An enlarged thyroid gland from any cause is called goiter. Cretinism (congenital hypothyroidism) T3 and T4 are among the most important developmental hormones for the nervous system. (1) Formation of axon terminals. (2) Production of synapses. (3) Growth of dendrites. (4) Formation of myelin. Dwarfism Cretinism I. Hypopituitarism Hypothyroidism II. GH T4, T3 III. Short stature, smart look Short stature, ugly look Proportionate body parts Disproportionately small body parts IV. Mentally normal Mentally retarded (IQ normal) (low IQ) V. Sexual infantilism Sexual infantilism small gonads Autoimmune thyroiditis Autoimmune thyroiditis is autoimmune disruption of the normal function of the thyroid gland. Hashimoto’s disease, in which cells of the immune system called T cells attack and destroy thyroid tissue. Hashimoto’s disease is more common in women and can slowly progress with age. Sex and the City's Kim Cattrall has Hashimoto's disease Dr Hakaru Hashimoto Hyperthyroidism (thyrotoxicosis) (1) Hormone-secreting tumors of the thyroid (rare) (2) An autoimmune disease called Grave’s disease (most common) Overstimulation of the growth and activity of the thyroid gland. Hyperthyroid patients tend to have heat intolerance. (1) Treated with drugs that inhibit thyroid hormone synthesis. (2) Surgical removal of the thyroid gland. (3) Destroying a portion of the