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Chapter 10: Endocrine System Principles of Chemical Communication Chemical Messengers  allow cells to communicate with each other to regulate bodily activities  Produced by glands Glands - consist of epithelial cells that specialize in secretion Classes of chemical Messengers 1 chemical messenger ...

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Chapter 10: Endocrine System Principles of Chemical Communication Chemical Messengers  allow cells to communicate with each other to regulate bodily activities  Produced by glands Glands - consist of epithelial cells that specialize in secretion Classes of chemical Messengers 1.Autocrine chemical messenger  stimulates the cell that originally secreted it / sometimes nearby cells of the same type.  EX: those secreted by white blood cells during an infection.  Several types of white blood cells can stimulate their own replication so that the total number of white blood cells increases rapidly 2. Paracrine chemical messengers  act locally on nearby cells.  These chemical messengers are secreted by one cell type into the extracellular fluid and affect surrounding cells of a different type.  EX: histamine, released by certain white blood cells during allergic reactions.  Histamine stimulates vasodilation in nearby blood vessels. 3. Neurotransmitters  are chemical messengers secreted by neurons that activate an adjacent cell, whether it is another neuron, a muscle cell, or a glandular cell.  Neurotransmitters are secreted into a synaptic cleft, rather than into the bloodstream Therefore, in the strictest sense neurotransmitters are paracrine messengers, but for our purposes it is most appropriate to consider them as a separate category. 4. Endocrine chemical messengers.  are secreted into the bloodstream by certain glands and cells, which together constitute the endocrine system.  These chemical messengers affect cells that are distant from their source. Functions of the Endocrine System 1. Metabolism 2. Control of food intake and digestion ■ Regulates level of satiety (fullness) and breakdown of food into nutrients 3. Tissue development 4. Ion regulation ■ Regulates solute concentration of the blood 5. Water balance 6. Heart rate & blood pressure regulation 7. Control of blood glucose and other nutrients 8. Control of reproductive functions 9. Uterine contractions and milk release 10. Immune system regulation Characteristics of the Endocrine System  Composed of endocrine glands and specialize endocrine cells located through out the body  Endocrine gland and cells - secrete hormones  Hormones - minute amounts of chemical messenger secreted into the bloodstream rather than into a duct.  Target Tissue (effectors) specific site where hormones produce a particular response of the target tissue.  Endocrine – Greek word o Endo – within o Krino – secrete  Endocrine glands are not to be confused with exocrine glands  Exocrine glands - have ducts that carry their secretions to the outside of the body or into a hollow organ (stomach/intestine) o i.e. saliva, sweat, breast milk, digestive enzymes Hormones  Greek word – Hormon = to set in motion  regulate almost every physiological process in our body. Chemical Nature of Hormones  Hormones fit into one of two chemical categories: lipid-soluble hormones and water-soluble hormones, a distinction based on their chemical composition, which influences their chemical behavior.  Cell Membrane - selective permeable phospholipid bilayer that excludes water soluble molecules, but

with its target, and its removal from the body—is dependent on the hormone’s chemical nature.  Within the two chemical categories, hormones can be subdivided into groups based on their chemical structures. o Steroid hormones: derived from cholesterol o Thyroid hormones: derived from the amino acid tyrosine o Other hormones: categorized as amino acid derivatives, peptides, or proteins. 1.Lipid-Soluble Hormones  Non-polar  steroid, thyroid, fatty-acid derivatives hormones such as certain eicosanoids. Transport  small molecules and are insoluble in water-based fluids (plasma of the blood)  Travel in bloodstream attached to binding proteins,  Binding proteins – transport and protect hormones.  Lipid-soluble hormones are degraded slowly and are not rapidly eliminated from the circulation. (lifespan: few days to several weeks)  Without the binding proteins, lipid-soluble hormones would quickly diffuse out of capillaries and be degraded by enzymes of the liver and lungs or be remove from the body by the kidneys.  Circulating Hydrolytic enzymes - can metabolize free lipidsoluble hormones. The breakdown products are then excreted in the urine/bile 2.Water-Soluble Hormones  Polar  protein, peptide, amino-acid derivatives Transport  Because water-soluble hormones can dissolve in blood, many circulate as free hormones, meaning that most of them dissolve directly into the blood and are delivered to their target tissue without attaching to a binding protein  Because many water-soluble hormones are quite large, they do not readily diffuse through the walls of all capillaries; therefore, they tend to diffuse from the blood into tissue spaces more slowly.  Organs regulated by some protein hormones have very porous or fenestrated capillaries – to aid in delivery of these hormones to individual cells  Other water-soluble hormones are quite small and require attachment to a larger protein to avoid being filtered out of the blood.  Short half-lives because they are rapidly degraded by enzyme called proteases.  The kidneys then filter the hormone breakdown products from the blood.  Hormone target cells also destroy water-soluble hormones. (Some take up cell through endocytosis)  Once the hormones are inside the target cell, lysosomal  enzymes degrade them.  Often, the target cell recycles the amino acids of peptide and protein hormones and uses them to synthesize new proteins.  Hormones with short half-lives normally have concentrations that change rapidly within the blood and tend to regulate activities that have a rapid onset and short duration.  However, some water-soluble hormones are more stable in the blood than others.  In many instances, protein and peptide hormones have a carbohydrate attached to them, or their terminal ends are modified - These modifications protect them from protease activity to a greater extent than water-soluble hormones lacking such modifications.  In addition, some water- soluble hormones also attach to binding proteins and therefore circulate in the plasma longer than free water-soluble hormones do. Control of Hormone Secretion  Blood level of most hormones fluctuates within homeostatic range due to negative-feedback mechanisms (positive feedback systems also regulate blood hormone levels in a few instances)

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allows lipid-soluble molecules to pass through Therefore, the entire basis of a hormone’s metabolism—its transport in the blood, its interaction

Stimulation of Hormone Release 1) Control by Humoral Stimuli

● Blood-borne chemicals can directly stimulate the release of some hormones ● Humoral refers to body fluids, including blood ● Sensitive to blood levels of particular substances (glucose, calcium, and sodium) Examples: o Parathyroid hormone (PTH) → blood level of a particular chemical changes (calcium) o Antidiuretic hormone (water conservation hormone) → elevated concentration of blood solutes o Insulin (pancreas) → secreted when high level of glucose o Aldosterone (adrenal cortex) → secreted when level of potassium elevated 2)Control by Neural Stimuli ● action potentials → neurons → neurotransmitter into synapse with the cells that produce the hormone → neurotransmitter stimulates cells to increase hormone secretion ● Neuropeptides  neurons that secrete chemical messengers directly into the blood when they are stimulated  Specialized neuropeptides stimulate hormone secretion from other endocrine cells and are called releasing hormones: a term usually reserved for hormones from the hypothalamus. Example: in response to stimuli, such as stress or exercise, the sympathetic division of the autonomic nervous system stimulates the adrenal gland to secrete: epinephrine & norepinephrine → help the body respond to the stimulus. Responses include: an increased heart rate and, in turn, increased blood flow through the exercising muscles. *When the exercise stops, the neural stimulation declines and the secretion of epinephrine and norepinephrine decreases. 3)Control by Hormonal Stimuli ● Occurs when a hormone secreted stimulates the secretion of other hormones Example: o Tropic Hormones - hormones from the anterior pituitary gland / stimulates the secretion of another hormone. ■ These hormones are part of a process in which a releasing hormone from the hypothalamus stimulates release of tropic hormone from pituitary gland. ■ The anterior pituitary tropic hormone then travels to another endocrine gland and stimulates release of third hormone. o Hormones from the hypothalamus and anterior pituitary regulate the secretion of thyroid hormones from the thyroid gland. Inhibition of Hormone Release  Stimulating hormone secretion is important, but inhibiting hormone release is also important 1) Inhibition of Release by Humoral Stimuli ● Often when a hormone’s release is sensitive to presence of humoral stimulus, there exists a companion hormone whose release is inhibited by same humoral stimulus ■ Companion hormone – effects oppose those of the secreted hormone and counteract the secreted hormone’s actions EX: o Adrenal cortex → Aldosterone → raises BP o Atrial of the heart → Atria Natriuretic Peptide (ANP) → lowers BP 2) Inhibition of Release by Neural Stimuli ● Neurons inhibit targets just as they stimulate target ● If the neurotransmitter is inhibitory, the target endocrine gland does not secrete its hormone 3) Inhibition of Release by Hormonal Stimuli ● Some hormones prevent secretion of other hormones, which is a common mode of of hormone regulation. EX: o inhibiting hormones - hormones from hypothalamus that prevent secretion of tropic hormones from pituitary gland o Thyroid hormones can control their own blood levels by inhibiting their pituitary tropic hormone. Without the original stimulus, less thyroid hormone is released Regulation of Hormone Levels in Blood 1. Negative Feedback  Most hormones are regulated by negative-feedback mechanism

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and there is adequate hormone to activate target cell The hormone may inhibit the action of other, stimulatory hormones to prevent the secretion of the hormone in question. Thus, it is a self-limiting system

EX: Thyroid hormones inhibit the secretion of their releasing hormone from the hypothalamus and their tropic hormone from the anterior pituitary. 2. Positive Feedback  Some hormones, when stimulated by tropic hormone, promote synthesis and secretion of tropic hormone in addition to stimulating target cell  In turn, this stimulates further secretion of the original hormone. Thus, it is a self-propagating system EX:  prolonged estrogen stimulation promotes a release of the anterior pituitary hormone responsible for stimulating ovulation. Hormone Receptors & Mechanisms of Action ● Receptors: protein molecule on cell surface or within cytoplasm that binds to a specific factor like a hormone, neurotransmitter, drug, or antigen ● A hormone can only stimulate the cells that have the receptor for that hormone ● Receptor site: The portion of each receptor molecule where a hormone bind ● Shape and chemical characteristics of receptor sites allow only a specific hormone to bind to it → ● Specificity - The tendency for each type of hormone to bind to one type of receptor, and not to others Classes of Receptors 1. Lipid-Soluble hormones: bind to Nuclear Receptors  lipid-soluble hormones tend to be relatively small and are all nonpolar (can freely cross cell membrane).  diffuse through the cell membrane and bind to nuclear receptors (found incell nucleus)  Nuclear receptors can also be in cytoplasm, but move to nucleus when activated  When hormones bind to nuclear receptors, hormonereceptor complex interacts w/ DNA in nucleus or w/ cellular enzymes to regulate transcription of genes in target tissue (takes several minutes to several hours)  Lipid-Soluble hormones have rapid effects (less than a minute) on target cells due to membrane-bound receptors instead of nuclear receptors Examples of hormones that bind to nuclear receptors: o Thyroid hormones and Steroid Hormone (Testosterone, Estrogen, Progesterone Aldosterone, Cortisol) 2. Water-Soluble hormones: bind to Membrane-Bound Receptors  water-soluble hormones are polar (they cannot pass through the cell membrane)  Instead, they interact w/ membrane-bound receptors (proteins that extends across the cell membrane w/ their hormone-binding sites exposed on the cell membrane’s outer surface)  When hormone binds to receptor on outside of cell membrane, hormone-receptor complex initiates a response inside the cell. Examples of hormones that bind to membrane-bound receptors: o Proteins, peptides, amino-acid derivatives (epinephrine, norepinephrine) Action of Nuclear Receptors ● Lipid Soluble Hormones: stimulate protein synthesis ● After lipid-soluble hormones diffuse across plasma membrane and bind to receptors, hormone-receptor complex binds to DNA to produce response ● Hormone-response elements – are receptors that bind to DNA / has finger like projections that recognize/bind to specific nucleotide sequences in DNA ● Transcription factor – formed by a combination of the hormone and its receptor forms / When the hormone-receptor complex binds to the hormone response element, it regulates transcription of specific mRNA molecules ● Newly formed mRNA moves to cytoplasm to be translated into specific proteins at the ribosomes ● New proteins produce the hormone’s effect at the target cell EX: o Testosterone - stimulates the synthesis of proteins 

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Hormone s secretion is inhibited by the hormone itself once blood levels have reached proper point

that are responsible for male secondary sex

characteristics, (formation of muscle mass and the typical male body structure). o Steroid hormone aldosterone - affects its target cells in the kidneys by stimulating the synthesis of proteins that increase the rate of Na+ and K+ transport. The result is a reduction in the amount of Na+ and an increase in the amount of K+ lost in the urine. o Other hormones that produce responses through nuclear receptor mechanisms include thyroid hormones and vitamin D. ● Target cells that synthesize new protein molecules in response to hormonal stimuli normally have a latent period of several hours between time the hormones bind to receptors and the time responses are observed ● During this latent period, mRNA and new proteins are synthesized. ● Hormone-receptor complexes are eventually degraded within the cell, limiting length of time hormones influence the cell's activities and the cells slowly return to their previous functional states. Membrane-Bound Receptors & Signal Amplification ● Cell membrane: contains proteins embedded in the phospholipid bilayer ● Membrane-bound receptors are ex. of membrane protein Membrane-bound receptors can activate responses in 2 ways: 1. Some receptors alter activity of G proteins at inner surface of cell membrane 2. Other receptors directly alter activity of intracellular enzymes ● Activation of G proteins / intracellular enzyme, elicits specific response in cells, including the production of molecules called second messengers (produced inside a cell once a ligand binds to its membrane-bound receptors; activates specific cellular process inside the cell in response to the hormone) ● Second messenger systems - coordinated set of events EX: Cyclic adenosine monophosphate AMP (cAMP) 1. Membrane-Bound Receptors That Activate G Proteins 2. G Proteins That Interact WIth Adenylate Cyclase Signal Amplification ● Hormones that stimulate synthesis of second messengers (watersoluble hormones) can produce an instantaneous response since the response proteins are already present! ● Each receptor produces a large number of second messengers, leading to a cascade effect and amplification of the hormonal signal! Endocrine Glands and Their Hormones Pituitary and Hypothalamus ■ Pituitary (hypophysis)→ small gland about a size of a pea/ rests in depression of sphenoid bone inferior to hypothalamus; “master gland” Anterior Pituitary- made up of epithelial cells from embryonic oral cavity; indirectly connected to hypothalamus via blood vessels Posterior Pituitary– an extension of the brain, composed of nerve cells ■ Hypothalamus → an important autonomic nervous system and endocrine control center of brain, located below thalamus ● Connected to pituitary gland via infundibulum ● Controls pituitary gland via hormonal control & direct innervation ● Controls joy, anger, chronic stress and more! Hormonal Control of the Anterior Pituitary ○ Neurons of hypothalamus produce/secrete neuropeptides that act on anterior pituitary gland ■ Act as either releasing hormones or inhibiting hormones by traveling through hypothalamic-pituitary portal system Direct Innervation of the Posterior Pituitary ○ Stimulation of neurons within hypothalamus controls secretion of hormones from posterior pituitary ■ Cell bodies of these neurons are in hypothalamus, axons extend through infundibulum to the posterior pituitary ○ Hormones are produced in nerve cell bodies and transported through the axons to the posterior pituitary where they are stored in the axon endings Thyroid Gland ○ Highly vascular ○ Secrete thyroid hormones which bind to nuclear receptors and regulate rate of metabolism ■ Synthesized and stored within gland in thyroid follicles where the hormones attach to thyroglobulin (protein) ■ Between follicles is network of loose connective tissue that contains “C Cells” which secrete Calcitonin

○ Thyroid hormones have a negative-feedback effect on hypothalamus and pituitary ■ Increasing levels of thyroid hormones inhibit secretion of TSH releasing hormone from hypothalamus and inhibit TSH secretion from anterior pituitary gland ● A loss of negative-feedback would result in excess TSH, causing them to enlarge (goiter) Hypothyroidism: lack of thyroid hormone secretion ■ Cretinism: appears in children; results in mental retardation, short stature, and abnormally formed skeletal structure ■ In adults, lack of thyroid hormone results in lower metabolic rate, sluggishness, and myxedema (accumulation of fluid) Hyperthyroidism: elevated rate of thyroid hormone secretion ■ Causes increased metabolic rate, extreme nervousness, chronic fatigue Graves Disease: abnormal proteins produced by immune system similar in structure/function to TSH ● Causes bulging of the eyes → exophthalmia ○ Thyroid gland requires iodine to synthesize thyroid hormones ■ Iodine is taken up by thyroid hormones ● If lacking iodine, production/secretion of thyroid hormones decrease! ■ Number near T indicates how many iodine atoms there are ● Lack of iodine results in reduced T3 and T4 synthesis ○ Parafollicular cells of thyroid gland release calcitonin in addition to thyroid hormones Parathyroid Glands (4) ○ Located in posterior wall of thyroid gland ○ Secrete parathyroid hormone (PTH) ■ Essential for helping to regulate blood calcium levels (more important than calcitonin) ■ Has many effects: 1. PTH binds to membrane-bound receptors of renal tubule cells, which increases active vitamin D formation. Vitamin D causes epithelial cells of intestine to increase calcium absorption a. (Vitamin D: skin → liver → kidneys) 2. PTH binds to receptors on osteoblasts. Substances released by osteoblasts increase osteoclast activity and cause resorption of bone tissue to release calcium into the circulatory system 3. PTH binds to receptors on cells of the renal tubules and decreases the rate at which calcium is lost in urine 4. PTH acts on its target tissues to raise blood calcium levels to normal ○ Hyperparathyroidism: high rate of PTH secretion ○ Soft bones, less excitable muscle/nerve cells (fatigue), kidney stones ○ Hypoparathyroidism: low rate of PTH secretion ○ Results from injury to or surgical removal of thyroid and parathyroid glands ○ Highly excitable muscle/nerve cells → spontaneous action potentials (cramps, tetanus) → respiratory muscles → breathing stops → death Adrenal Glands (2) ○ Located superior to each kidney ○ Has an adrenal medulla (inner) & adrenal cortex (outer) ■ Inner and outer parts function as separate endocrine glands Adrenal Medulla ■ ...