Endocrine System Lecture Notes PDF

Chapter 18 – Endocrine System Dr. Gee Body Temperature Homeostasis  The Body Systems & Homeostasis Nervous & endocrine systems coordinate the other organ systems. Nervous system is faster, but the effects of the endocrine system last longer. Endocrine system secretes...

Chapter 18 – Endocrine System Dr. Gee Body Temperature Homeostasis  The Body Systems & Homeostasis Nervous & endocrine systems coordinate the other organ systems. Nervous system is faster, but the effects of the endocrine system last longer. Endocrine system secretes hormones - chemical messengers that travel in blood. Mechanisms of Intercellular Communication 1) Direct communication Ions, small solutes, lipid-soluble materials shared between cells of the same type in physical contact via Gap Junctions. Examples: 1) Coordinates ciliary movement between epithelial cells. 2) Coordinates the contractions of cardiac muscle cells. Mechanisms of Intercellular Communication 2) Paracrine communication Chemical messeges released by cells and affect other cell types locally within the same tissue without being transported in blood. Example: Somatostatin released by some pancreatic cells to inhibit the release of insulin by other pancreatic cells. Mechanisms of Intercellular Communication 3) Autocrine communication Chemical messages, autocrines, released by cells that have a local effect on the same cell from which they were released. Example: Prostaglandins secreted by smooth muscle cells cause the same cells to contract.  Mechanisms of Intercellular Communication 4) Endocrine communication Chemical messengers, hormones, produced by cells of endocrine glands that enter the bloodstream and affect distant target cells that express receptors that allow for binding of a specific hormone and relays the message to the inside of the cell and causes a response. Example: Epinephrine is released from the adrenal gland, travels through the blood, binds to cells expressing the receptors, but causes different cellular responses in different cell types.  Same hormone can trigger multiple types of cellular responses Effects of Epinephrine “Fight or flight response” Differing effects are the result of different proteins associated with the signal transduction pathway in different cell types.  Hormones Hormone characteristics: Produced in small quantities. Secreted into intercellular space. Transported some distance via the blood & cardiovascular system. Acts on target tissues elsewhere in body. Regulate activities of body structures.  Chemical Nature of Hormones Water-soluble Transported as free hormones. Short half-life. Include proteins, peptides, and amino acid derivatives. Lipid-soluble Transported with binding proteins. Therefore, have long half-life. Include steroids, amino acid derivatives, and fatty acid derivatives. Effect of Binding Proteins  Hormones Hormone characteristics: 1) Stability Half-life: length of time it takes for half a dose of substance to be eliminated from the cardiovascular system. Long half-life: regulate activities that remain at a constant rate through time. Lipid soluble and travel in plasma attached to proteins. Short half-life: have a rapid onset and short duration. water-soluble hormones as proteins, epinephrine, norepinephrine. 2) Communication Interaction with target cell. 3) Distribution Hormones can be bound to plasma proteins called binding proteins (lipid soluble hormones). Hormones can be dissolved in blood plasma and transported in unbound (free hormones) form (water-soluble hormones that are polar). Hormones are distributed quickly because they circulate in the blood. Mechanisms of Intercellular Communication 5) Synaptic Communication Neurotransmitter - produced by neurons and secreted into extracellular spaces by presynaptic nerve terminals. travels short distances. influences postsynaptic cells. specialized form of paracrine signaling. Example: Acetylcholine, Norepinephrine Comparison of the Nervous & Endocrine Systems Similarities: 1. Both systems regulate and coordinate the activities of essentially all body structures to achieve/maintain homeostasis. 2. Both systems associated with the brain. Hypothalamus. 3. May use same chemical messenger as neurotransmitter and hormone. Example: epinephrine, norepinephrine. 4. Two systems act cooperatively to regulate body processes. 5. Some neurons secrete hormones. Neuropeptides. 6. Neurotransmitters and hormones can affect their targets through receptors linked to G proteins. Comparison of the Nervous & Endocrine Systems Differences: 1) Mode of transport. Axon vs. blood. 2) Speed of response. Nervous – instant/milliseconds. Endocrine – delayed/seconds. 3) Duration of response. Nervous – milliseconds/seconds. Endocrine – minutes/days.  Principles of Chemical Communication Characteristics of the endocrine system. Composed of endocrine glands that secrete chemical messengers (hormones) into the blood. NOTE: NOT exocrine glands, which have ducts that carry their secretions into a hollow organ or outside the body (saliva, sweat, breast milk, and digestive enzymes).  Glands (Review) One or more specialized epithelial cells that make and secrete a product. 2 types: exocrine & endocrine. 1) Exocrine glands secrete products into hollow organs or ducts. Sweat glands, mammary glands, salivary glands 2) Endocrine glands secrete products (hormones) into the (a) Goblet cells. These unicellular glands secrete bloodstream; have no ducts. mucus. (b) Sweat gland. This simple gland consists of a coiled tube. Its wall is constructed of simple cuboidal epithelium. Pituitary gland, thyroid gland (c) Parotid salivary gland. Compound glands, like the parotid, have branched ducts.  Patterns of Hormone Secretion Chronic hormone secretion Maintenance of relatively constant concentration of hormone. Thyroid hormone. Acute hormone secretion Rapid ↑ for a short time in response to a specific stimulus, whereby smaller stimulus does not activate as much hormone secretion as larger stimulus Epinephrine in response to stress. Insulin in response to meal. Episodic hormone secretion Stimulated so that ↑ and ↓ at a consistent time and amount Female reproductive hormones.  Control of Hormone Secretion Most hormones are regulated by negative-feedback. However, some are regulation by positive feedback. Most hormones are not secreted at constant rate, but hormone secretion is regulated by 3 different methods. 1) Humoral regulation 2) Neural regulation 3) Hormonal regulation 1) Humoral Regulation of Hormone Secretion Humoral control: the action of a substance other than a hormone on an endocrine gland.  2) Neural Regulation of Hormone Secretion Neural control: by the nervous system.  3) Hormonal Control of Hormone Secretion Hormonal control: control of secretory activity of one endocrine gland by hormone secreted by another endocrine gland. 1. Neurons in the hypothalamus release stimulatory hormones, called releasing hormones. Releasing hormones travel in the blood to the anterior pituitary gland. 2. Releasing hormones stimulate the release of tropic hormones - hormones that act on other endocrine glands to produce their hormones, from the anterior pituitary gland, which travel in the blood to their target endocrine cell.  3) Hormonal Control of Hormone Secretion Hormonal control: control of secretory activity of one endocrine gland by hormone or neurohormone secreted by another endocrine gland. 3. The target endocrine cell secretes its hormone into the blood, where it travels to its target and produces a response. 4. The hormone from the target endocrine cell also inhibits the hypothalamus and anterior pituitary from secreting the releasing hormone and the tropic hormone. This is negative feedback. 5. In some instances, the hypothalamus can also secrete inhibiting hormones, which prevent the secretion of anterior pituitary tropic hormones.  Negative Feedback by Hormones 1. The anterior pituitary gland secretes a Hypothalamus tropic hormone (other endocrine glands as a target), which travels in the blood to the target endocrine cell. 2. The hormone from the target endocrine cell travels to its target. 3. The hormone from the target endocrine cell also has a negative- feedback effect on the anterior pituitary and hypothalamus and decreases secretion of the tropic hormone.  Positive Feedback by Hormones 1. The anterior pituitary gland Hypothalamus secretes a tropic hormone (other endocrine glands as a target), which travels in the blood to the target endocrine cell. 2. The hormone from the target endocrine cell travels to its target. 3. The hormone from the target endocrine cell also has a positive-feedback effect on the anterior pituitary and hypothalamus and increases the secretion of the tropic hormone. Hormone Receptors & Mechanisms of Action Target Tissue Specificity & Response Portion of molecule where hormone binds is called binding site. If the molecule is a receptor (like in a cell membrane) the binding site is called a receptor site. The hormone/receptor site is specific. For example: epinephrine cannot bind to the receptor site for insulin. The purpose of binding to target tissue is to elicit a response in the target cell.  Decrease in Receptor Number Normally, receptor molecules are degraded and replaced on a regular basis. Down-regulation Rate at which receptors are synthesized decreases in some cells after the cells are exposed to a hormone. The binding of hormones with its receptors can increase the rate at which receptor molecules are degraded. This combined form is taken into the cell by phagocytosis and then broken down.  Increase in Receptor Number Up-Regulation Some stimuli can cause an increase in the synthesis of receptors for a hormone, thus increases sensitivity to that hormone. For example: FSH stimulation of the ovary causes an increase of LH receptors. Ovarian cells are now more sensitive to LH, even if the concentration of LH does not change. This causes ovulation. A) Nuclear Receptors Lipid-soluble hormones: Bind to nuclear receptors. Lipid soluble and relatively small molecules pass through the plasma membrane. React either with enzymes in the cytoplasm or with DNA to cause transcription and translation. Examples: Thyroid hormones, testosterone, estrogen, progesterone, aldosterone, and cortisol.  Nuclear Receptor Model 1. Lipid–soluble hormones diffuse through the plasma membrane. 2. Lipid-soluble hormones bind to nuclear receptors. Some lipid- soluble hormones bind receptors in the cytoplasm and then move into the nucleus. 3. The hormone–receptor complex binds to a hormone response element on the DNA, acting as a transcription factor.  Nuclear Receptor Model 4. The binding of the hormone– receptor complex to DNA stimulates the synthesis of messenger RNA (mRNA), which codes for specific proteins. 5. The mRNA leaves the nucleus, passes into the cytoplasm of the cell, and binds to ribosomes, where it directs the synthesis of specific proteins. 6. The newly synthesized proteins produce the cell's response to the lipid–soluble hormones—for example, the secretion of a new protein.  B) Membrane-bound Receptors Water-soluble hormones: Bind to membrane-bound receptors: Integral membrane proteins with receptor site on the extracellular surface. Interact with hormones that cannot pass through the plasma membrane. Water-soluble or large-molecular-weight hormones. Attachment of hormone causes an intracellular reaction. Examples: Large proteins, glycoproteins, polypeptides; smaller molecules like epinephrine and norepinephrine.  Action of Membrane-Bound Receptors Intracellular mediators - ions or molecules that enter cell or are produced in cell. Some intracellular mediators are called second messengers: Cyclic adenosine monophosphate (cAMP) Cyclic guanosine monophosphate (cGMP) Diacylglycerol (DAG) Inositol Trisphosphate (IP3) Ca2+ Can be produced because of G protein activation. Regulate intracellular enzyme activities. Receptors that Activate G Proteins G Proteins That Interact with Adenylate Cyclase 1. After a water-soluble hormone binds to its receptor, the G protein is activated. 2. The activated α subunit, with GTP bound to it, binds to and activates an adenylate cyclase enzyme, so that it converts ATP to cAMP. 3. The cAMP can activate protein kinase enzymes, which phosphorylate specific enzymes that are also then activated. The chemical reactions catalyzed by the activated enzymes produce the cell's response. 4. Phosphodiesterase enzymes inactivate cAMP by converting cAMP to AMP.  Hormone response via second messenger, cAMP Note: epinephrine (adrenaline) = hormone in fight/flight response  G Proteins That Cause Synthesis of DAG and IP3 1. Epinephrine binds to its receptor in the smooth muscle plasma membrane. 2. The G protein is activated. The activated  subunit with GTP bound to it separates from the  and β subunits. 3. The activated  subunit then binds with phospholipase C, which acts on phosphoinositol bisphosphate (PIP2) (a LIPID) and produces inositol triphosphate (IP3) and diacylglycerol (DAG) (Both second messengers).  G Proteins That Cause Synthesis of DAG and IP3 4. IP3 releases Ca2+ from the endoplasmic reticulum or opens Ca2+ channels in the plasma membrane. 5. Calcium ions then regulate enzyme activity. 6. DAG regulates enzymes such as protein kinases and those that synthesize prostaglandin. These responses increase smooth muscle contraction.  Signal transduction via second messengers 2) DAG and 3) IP3 Diacylglycerol (DAG) stays in membrane → activates protein kinase C (PKC) → PKC phosphorylates target proteins IP3 diffuses to ligand-gated calcium channels in ER membrane PIP2 = → Ca2+ released a membrane phospholipid Some signaling molecules trigger 4) Ca2+ movement Another Example: acetylcholine (neurotransmitter) stimulates muscle cell to release internal Ca2+ stores important for muscle contraction. Endoplasmic Reticulum (smooth) Extracellular Ca2+ Fluid Ca2+ [High Ca2+] Ca2+ [High Ca2+] Cytoplasm Ca2+ Ca2+ [Low Ca2+] Ca2+ Ca2+ [High Ca2+] When signal is no longer present, Ca2+ pumps Ca2+ remove Ca2+ from cytoplasm Mitochondria Probable mechanisms of egg activation Roles of inositol phosphate (IP3) in releasing calcium from the endoplasmic reticulum and the initiation of development G Proteins Opening Ion Channels  Membrane-Bound Receptor Directly Activating an Intracellular Mediator 1. The water-soluble hormone binds to its receptor. 2. At the inner surface of the plasma membrane, guanylate cyclase is activated to produce cGMP from GTP. 3. Cyclic GMP is an intracellular mediator that alters the activity of other intracellular enzymes to produce the response of the cell. 4. Phosphodiesterase enzymes inactivate cGMP by converting cGMP to GMP.  Viagra is a phosphodiesterase (PDE5) inhibitor Location: bloods vessels in penis (corpora cavernosa) ViagraTM inactivates phosphodiesterase 5 (PDE5) thus blocking conversion of cGMP to GMP so that relaxation of smooth muscle cells (SMCs) and blood vessels can continue longer. (↑ Blood flow)  Viagra is a phosphodiesterase (PDE5) inhibitor Location: bloods vessels in penis (corpora cavernosa) (SMC) Nitric oxide = Signaling molecule ↑ Blood flow SMC contraction ↓ Blood flow Viagra ViagraTM inactivates phosphodiesterase 5 (PDE5) thus blocking conversion of cGMP to GMP so that relaxation of smooth muscle cells (SMCs) and blood vessels can continue longer. (↑ Blood flow) Receptors That Phosphorylate Intracellular Proteins Hormones bind to membrane- bound receptors. Part of receptor protein on inside of membrane acts as an enzyme to phosphorylate proteins. For example: insulin receptors bound to insulin cause phosphorylation of proteins and cell responds to presence of insulin.  Signal Amplification A single hormone molecule can activate many second messengers, each of which activates enzymes that produce an enormous amount of final product.