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-Chapter 15: The Endocrine System-The endocrine system and nervous system are the major information centers between different cells and tissues of the body. -________________: “President” of the Endocrine System >inferior region contains the Pituitary Gland-________________: “Vice President” of the Endocrine System >has 3 lobes: Anterior, Intermediate, Posterior-________________: “citizens”, includes the Adrenal Gland, Thyroid Gland, Ovaries, Testes-Mechanisms of Hormone Secretion-Endocrine Hormones: a chemical substance which is produced and secreted by the cells of an Endocrine gland and released into _______________, which carries it to its target cells. Endocrine hormones all require specific receptors on their target cells, without receptors they cannot bind to the target cell, and the cell will not carry out the physiological action that the hormone is signaling for (stimulation or inhibition).Exocrine Hormone: a chemical substance produced in exocrine cells that is NOT secreted into the circulatory system but instead secreted into interstitial fluid, the surface of tissue, or into a cavity. This includes: -Pancreatic enzymes secreted by: -Saliva secreted by: -Sweat secreted by: -Exocrine hormones are produced in the _______ and secreted out of the gland by ducts (Pancreatic duct, Common Bile duct, Parotid duct, etc.), which open into the cavity/surface of the target organ/tissue. >___________ Hormones: stimulate/inhibit the actions of neighboring target cells. Target cells may or may not be hormone-producing. For example: Somatostatin inhibits Insulin secretion in Pancreatic β-cells. >___________ Hormones: give feedback to their own cell to stimulate/inhibit cellular activity. They bind to their own receptors on their own cell surface. >___________ Hormones: stimulate/inhibit cellular activity inside their own cell without being secreted. For example: Insulin can inhibit its own secretion from pancreatic β-cells. -Hormone Synthesis-___________ hormones: Are produced the same way as other cellular protein products. Includes GH, Prolactin, and PTH.___________ hormones: Are produced from cleaving off a portion from larger protein precursors. Includes Insulin, ACTH, and Glucagon. ___________ hormones: Are produced by “Organification”, the combination of Iodine and Tyrosine (residues of Thyroglobulin proteins), and the “Coupling” of the different molecules produced by those combinations.___________ hormones: Are produced from a cholesterol precursor molecule.-Protein Hormones vs Steroid Hormones-Binding Site: -Protein hormones bind to: -Steroid hormones bind to: Lipophobic vs Lipophilic: -Protein hormones: are -Steroid hormones: are Hydrophobic vs Hydrophilic: -Protein hormones: are -Steroid hormones: are Requires a Carrier/Transport molecule in the blood: -Protein hormones: _________ require a carrier, can ________________ in the blood -Steroid hormones: _________ require specific carriers to move through blood to reach their target cell -Thyroid hormones: _________require carriersDuration of the hormone action on their target cell: -Protein hormones: _________ because they have _______________________ -Steroid hormones: _______ because they ____________________________________ before bindingPrecursor: -Protein hormones: ________________ precursor -Steroid hormones: ________________ precursor -Thyroid hormones: ________________ precursor (an amide) -Hormone Receptors- -Cell surface receptors -are located on target cell membrane surface -are specific for _______________ and ______________ hormones -ex: Insulin, Growth Hormone, and Prolactin -Nuclear receptors (intracellular receptor) -are located inside the target cell at the nucleus -bind _______________ hormones and ______________ hormones -ex: Testosterone, Androgen, Estrogen, Progesterone, Aldosterone, Cortisol, T3, T4, and vitamin D-Hormone Effects-______________ Effects: When two or more different hormones have similar functions and effects on their target cell, and work in harmony for a specific outcome. For example: Aldosterone and Norepinephrine both increase blood pressure, and Cortisol and Insulin both regulate blood glucose.______________ Effects: When one hormone gives “permission” for the action of a second hormone. It can also enhance the responsiveness of a target cell to the second hormone, or it can increase the activity of the second hormone. ______________ Effects: When the binding of one hormone inhibits the effects of another. This effect is typically used when designing drugs like synthetic hormones, so they can recognize and bind to natural hormone receptors to block natural hormones from binding there (inhibits a process that may have become pathological). For example: Propranolol is an antagonist for β1 receptors by binding and blocking Norepinephrine from being able to bind.______________: act like natural hormones and bind to natural hormone receptors. For example: in Hormone Replacement Therapy, Growth Hormone (GH) receptors are bound by synthetic Growth Hormones to treat growth conditions like Dwarfism. -Four types of Cell Surface Receptors-1 – G-protein coupled receptor (GPCR):-G-protein is an intracellular protein connected to a receptor protein with __________________ domains >The receptor __________-terminal is exposed _________________ >The receptor __________ -terminal is exposed _________________-G-protein has 3 subunits: -when a hormone binds to the receptor, G-protein ____-subunit binds ___________________________ intracellularly for energy (using GTPase) to become activated. α-subunit binds ________________________ when inactive.-G-protein α-subunits can either be ______________________ or _______________________-G-proteins are coupled with other effector molecules that they pass activation signals along to for signal transduction to Second Messengers inside the cell. -Effector molecules include: -Second Messenger molecules include: -These are some molecules that bind GPCRs: >Catecholamines: Noradrenaline and Adrenaline >Prostaglandin >ACTH >Glucagon >PTH (parathyroid hormone) >TSH (Thyroid Stimulating Hormone)-For example: Norepinephrine’s effect on α1 G-Protein Coupled Receptor on the surface of smooth muscle cells of blood vessels: 1-Norepinephrine binds to its receptor and activates G-Protein α-S subunit. 2- α-S subunit then activates Phospholipase-C, which then activates IP3, which activates calcium-Calmodulin to increase calcium levels in the cell’s cytoplasm, which then binds to Troponin-C, and causes interactions between Actin and Myosin fibers resulting in a muscular contraction. 3-Muscle contraction is the reaction of the target cell to the binding of Norepinephrine. 2 - Growth factor receptor:-Is a receptor protein with its ____________-terminal exposed extracellularly as a ___________________ -has one ____________________ domain-its __________-terminal is intracellular and acts as a catalytic domain for ____________________ and the activation of its Second Messenger ____________________ when the receptor is bound by a hormone signal.-These receptors bind: -Insulin: decreases blood glucose level by facilitating glucose uptake into cell -Insulin Growth Factor (IGF)-Epidermal Growth Factor (EGF) >IGF and EGF are hormone cytokines involved in cell proliferation and cell growth3 - Cytokine receptor -A receptor protein specific for ______________________ binding -has its _________-terminal exposed ______________________ as a binding site-has _______ transmembrane domain-has its ____________-terminal exposed ________________ for effector activation of Second Messengers-When GH binds to the receptor, the association between the now activated receptor’s carboxyl-terminal and the Second Messenger protein _______ leads to conformational changes in the structure of ______ which activates its tyrosine kinase catalytic activity. This allows ______ to activate the next Second Messenger, ______________, which begins the signal transduction pathway towards a cellular reaction. 4 – Ligand-Regulated Transporter (Guanylyl cyclase receptor)-Are protein receptors that _______________ when they bind a ligand (hormones in this case) in order to open as a channel and allow specific ions to flow through.-The ions that flow through are considered ___________________________.-These receptors bind: >______________: a vasodilator, causes an increase in Nitric Oxide Synthase (NOS), which stimulates Guanylyl Cyclase (GC) activity to increase intracellular levels of cGMP (energy) to activate Protein Kinases (PKG) for vasodilation of the penile dorsal vein during erections >ANP (atrial natriuretic peptide): a vasodilator that decreases blood pressure mostly during Hypertension using a similar mechanism-Nuclear receptors--Receptors are specific for Steroid hormones, Vitamin D, Thyroid hormones, Retinoids, Fatty acids, Bile acids-The receptor’s ______-terminal has high amino-acid variation for specific control of target gene transcription-The receptor has a ______-binding domain, and a _________ -terminal that acts as a binding site as well as being able to control transcription.-These receptors control __________________, since they can bind to DNA on the promoters of target genes or to the transcription factors of target genes. -Binding of a signal stimulates an increase or decrease in target gene ______________________ into a protein product meant to be used for some function.-Steroid and Thyroid hormone mechanisms-Step 1 – Steroid or Thyroid hormones __________________ the target cell membraneStep 2 – hormone binds to the cytoplasmic site on its ___________ receptor proteinStep 3 – Nuclear receptor undergoes conformational changes to expose ______-binding site of the target geneStep 4 – The target gene is transcribed, resulting in an _________ sequence of that target geneStep 5 – The new ________ sequence is ___________ to produce a specific protein product that will satisfy the cellular physiological reaction to the binding of the initial hormone signal-ENDOCRINE SECRETIONS AND FUNTIONS--The Hypothalamus controls many things including body temperature, sleep, memory, learning, emotional and sexual behavior (associated with the Limbic System), Autonomic Nervous System, and Endocrine System.1 – CRH (Corticotropin Releasing Hormone): The blood vessel connecting the Hypothalamus and Anterior Pituitary, _____________________________________, releases Releasing Hormone (RH) from Hypothalamic nuclei into the Anterior Pituitary, which contains Trophic cells. ______ is released from Hypothalamus into the HPPS vessel and carried into the Anterior Pituitary, where there are ______________ cells. CRH binds to these cells on their membrane surface (activating ________ as a second messenger inside the cell) and the cells secrete __________________________________, which is then carried by the blood to the Adrenal Cortex (of the Adrenal Gland) in order to bind to Adrenal Cortex cell-surface ____________ receptors (with _______ second messenger) to stimulate secretion of: >Androgen: sex hormone seen in males and females (important in females to begin puberty) -sex hormone produced in the ____________________ of the Adrenal Cortex -binds to a Nuclear receptor -crucial hormone in puberty, involved in axillary and pubic hair growth, and acne >Aldosterone: increase NaCl and H2O reabsorption in Nephron, increases blood pressure & volume -is a “___________________” produced in the ____________________ of the Adrenal Cortex -binds to a Nuclear receptor in cells of the Collecting Tubule of Nephron -involved in the Renin-Angiotensin System -Increases NaCl, H2O, and HCO3- reabsorption, increases blood pressure -Increases excretion of H+ and K+ into urine -Activated when blood pressure is low >Cortisol: “stress hormone”, maintains blood glucose, metabolism and appetite -is a “________________” produced in the _____________________ of the Adrenal Cortex -binds to a Nuclear receptor -degrades proteins, suppresses immune system and inflammation -Increases Lipolysis (break down of lipids) -Stimulates gluconeogenesis2 – TRH (Thyrotropin Releasing Hormone): Released through HPPS and binds to surface receptors on ___________ cells in the Anterior Pituitary in order to stimulate the cells to secrete TSH (Thyroid Stimulating Hormone), which enters the blood to stimulate the Thyroid Gland to secrete T3 and T4 hormones. TRH can also stimulate the ____________________ to secrete Prolactin. >Prolactin: -in females: develops mammary glands for breastfeeding when pregnant, excess can cause infertility because it suppresses other sex hormones BUT during pregnancy Prolactin can inhibit menstruation and ovulation to avoid miscarriage of the fetus. -in males: helps control emotional and sexual behavior, excess can cause infertility because it suppresses other sex hormones -_______________ inhibits release of Prolactin -Uses ________ as a secondary messenger >TSH: binds to the surface of __________ cells in the Thyroid Gland (to a ________________ Receptor) and uses _______ as a secondary messenger. Helps control the development of fetal Thyroid Glands (along with the T3 and T4 it stimulates) and helps with the development of the Central Nervous System (including Brain), and bones. -T3 & T4: TSH stimulates production via _____________. Iodine (I2) and Tyrosine (from Thyroglobulin) combine and are catalyzed by ______________ to form (MIT) and (DIT) used to build T3 & T4. T3 and T4 have _________ receptors and control memory, learning, metabolism, heart rate, contractility, blood pressure and temperature. Can increase O2 consumption, glucose metabolism in the Liver, gluconeogenesis and glycogenolysis, can increase α1 & β1 receptor sensitivity to Norepinephrine 3 – GnRH (Gonadotropin Releasing Hormone): stimulates ________________ cells to secrete ___________________________ and ______________________. GnRH uses _____ as its second messenger. >FSH & LH in females: ______ level _______ during first 2 weeks of the menstrual cycle (the first phase – called the Follicular Phase) in order to mature and develop follicles in the ovaries into the Corpus Luteum around an ovum. Once they enter the mid-cycle (second phase) the ______ level _______ and the ____ level _________, because LH controls ovulation and the last step of follicle development-where it ruptures and releases an ovum. The freed ovum then migrates out of the ovary and into the fallopian tube to await possible fertilization (optimal time for fertilization is during ovulation at the mid-cycle). >FSH & LH in males: FSH has receptors on some cells in the testes, and controls maturation of sperm and Spermatogenesis from germ cells. When the rate of sperm production is too ______, Sertoli cells secrete _________ to prevent FSH from sending feedback to the Anterior Pituitary (for more FSH), in this way it inhibits further FSH secretion. LH has receptors on specific testicular cells called ___________. LH binding to these receptors stimulates secretion of Testosterone (used in reproductive regulation and puberty) >FSH uses ________surface receptors and _______ as a second messenger4 – GHRH (Growth Hormone Releasing Hormone): secreted by Hypothalamus into Anterior Pituitary to bind to cell-surface ______ receptors on _____________ cells to stimulate the secretion of GH (Growth Hormone). GH is also secreted by the Placenta in pregnant females. Uses ____ and ______ as second messengers. >Growth Hormone (GH): controls cell proliferation (increase in number of cells) & cell growth (cell size) in the ovum upon fertilization. GH binds to cell-surface _____________ Receptors and uses _______ and ____________________ as second messengers-HYPOTHALAMUS-The Hypothalamus is connected to the Pituitary Gland (also called the Hypophysis cerebri) in two ways:1-Hypothalamus & Anterior Pituitary gland:-Blood vessels of the Hypothalamic-Pituitary Portal System (HPPS) connect small sinusoid vessels in the infundibulum with the Primary Capillary Plexus in the ________________ of the Pituitary gland.-These vessels allow the Hypothalamus to control the Anterior Pituitary to secrete hormones that then influence peripheral endocrine tissues.-_____________________________ are carried from the Hypothalamus by HPPS vessels to their specific trophic cells in the Anterior lobe of the Pituitary. -the Trophic cells in the Anterior Pituitary are then stimulated to release specific ______________________ which the leave the Pituitary and enter the blood stream to bind and stimulate target cells on peripheral endocrine tissues (may stimulate them to secrete other hormones, such as T3 and T4 in thyroid, or stimulate them to perform an action).2-Hypothalamus & Posterior Pituitary gland:-The ______________ and ___________________ nuclei in the Hypothalamus have nerve fibers extending down into the Posterior lobe of the Pituitary gland.-Nuclei are stimulated and their axon terminals secrete ____________ and ________ in the Posterior Pituitary.-Hormone Secretion Feedback Systems- -When peripheral hormone levels decrease it sends __________ feedback to central hormones SH and RH to ____________ secretions. -When peripheral hormone levels increase it sends __________ feedback to central hormones SH and RH to ____________ secretions.-PITUITARY- -has 3 lobes: Anterior, Intermediate, Posterior-has many specific types of trophic cells that are stimulated by the Hypothalamus to secrete hormones.-once trophic cells secrete specific hormones, they enter the blood to find target tissueHormones of the anterior lobe of the pituitary: Growth hormone (GH) Adrenocorticotropic hormone (ACTH), Follicle- Stimulating hormone (FSH), Luteinizing hormone (LH), Thyroid- Stimulating hormone (TSH), Prolactin (PL)Hormones of the posterior lobe of the pituitary:-Antidiuretic hormone (ADH, also called “Vasopressin”)-Oxytocin-Inhibitory releasing hormones:-Hypothalamic neurotransmitters may also act as neurohormones such as: >_______________: inhibits Prolactin secretion from the Anterior lobe of the Pituitary >_______________: inhibits Growth Hormone secretion from the Anterior lobe of the Pituitary-Anterior Pituitary Hormones- 1 - TRH (Thyrotropin Releasing Hormone): secreted by Hypothalamus through HPPS vessels into the Anterior Pituitary where TRH binds to _____________ cell _______ receptor (using ____ as a Second Messenger) to stimulate the cell to secrete: -Thyroid stimulating hormone (TSH): Stimulates Thyroid gland for secretion of T3 and T4. -Prolactin (PL): >in females: during pregnancy Prolactin prepares the mammary gland for breast feeding and suppresses sex hormones such as FSH and LH to inhibit menstruation and ovulation. Non-pregnant females and males have small amounts of prolactin. >in males: Prolactin controls emotional behavior and sexual behavior. -Excess Prolactin suppresses sex hormones and causes infertility in both sexes -Hyperprolactinemia is treated with synthetic Dopamine (_______________)2 - CRH (Corticotropic Releasing Hormone) stimulates ______________ cells to secrete ACTH from the Anterior Pituitary lobe. -ACTH enters the blood to stimulate the Adrenal Cortex of the Adrenal Gland, which leads to secretion of: 3 - GHRH (Growth Hormone Releasing Hormone): uses _______ surface receptors and ______ and ______ second messengers to stimulate Somatotropic cells to secrete Growth Hormone (GH) from the Anterior lobe of the Pituitary gland. GH is also secreted by the Placenta in pregnant females. -Effect of GH (growth hormone): Binds to __________ cell-surface receptor and uses ______ and ________________ as second messengers. GH stimulates cell ______________ and cell ________ in child and in fetus (active during embryogenesis, and development of brain, heart, blood vessels, soft tissue). -GH levels increase in pregnancy & in childhood -GH levels decrease after puberty -GH excess during childhood may cause ___________, where the child grows extremely tall, and have an enlarged heart. This is usually treated preventatively with synthetic _________________. -excess GH secretion after puberty or in adults causes Acromegaly (enlarged face, hands, and feet) -GH deficiency can lead to ___________, which is treated with ____________________. 4 - GnRH (Gonadotropin Releasing Hormone): stimulates _____________________ to secrete Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) -Effect of FSH & LH in female: Receptors in the ________. Controls development of follicle and ovum during first two weeks of menstrual cycle, when FSH level increases which controls maturation or development of follicle. By the Midcycle (day 13, 14, or 15) FSH level decreases & LH level increases for the beginning of Ovulation. LH takes over last steps of maturation of follicle after FSH. LH causes the rupture of follicle cell, elimination of ovum from follicle, and the migration of ovum toward fallopian tube. After ovulation, if there is no sperm there is no pregnancy. -Effect of FSH & LH in male: FSH has receptors in the ___________, and controls development of sperm from germ cells. LH has receptors in the testicle on _________ cells, where it stimulates Testosterone secretion. Testosterone is important for the development of testicles in male fetus, development of external genitalia in fetus and child, and in the descent of testes from the abdominal cavity to the scrotum in the fetus. >Testosterone controls secondary sex characteristics: muscles, voice, libido >Testosterone: Controls body temp, increases red blood cell production, controls mood, sleep, appetite, body metabolism >Testosterone deficiency in the fetus leads a failure of testicular descent-Posterior Pituitary Hormones--Two nuclei (Supraoptic and Paraventricular) in the Hypothalamus contain the cell bodies of neurons, and their axons project into the Posterior Pituitary lobe. When stimulated, they produce and secrete 2 hormones from their axon terminals: >ADH (Antidiuretic Hormone): (also called Vasopressin) osmoreceptors in large blood vessels are sensitive to blood osmolarity and are stimulated when blood becomes too concentrated (possible dehydration). These osmoreceptors are under the control of two cranial nerves: ________________ and ________________________and they carry information about blood osmolarity to two Hypothalamic nuclei: Supraoptic nuclei and Paraventricular nuclei, which stimulates them to secrete ADH into the Posterior Pituitary when the blood volume is low (dehydrated). ADH is released into the blood and carried to the Renal System, where it binds to the ____________________ surface receptor on the Collecting Tubule of the Nephrons. This stimulates reabsorption of H2O into the Peritubular capillaries to decrease osmotic pressure in the tubules and increase blood volume by diluting the blood. This decreases urination and relieves dehydration. >Oxytocin: -in females: is important for lactation in mammary glands, and in the uterus it has receptors on the myometrial cells of the uterus smooth muscle layer (_______________) to control contractions during labor and childbirth. -in males: is important in the control of ejaculation and vasoconstriction-Adrenal gland--Adrenal glands (Suprarenal glands) are located on the upper pole of each ___________. -Each gland is 90% outer layer (________________) and 10% inner layer (__________________). -The Adrenal Cortex has 3 layers: >Zona glomerulosa: secretes >Zona fasciculata: secretes >Zona reticulata: secretes -Adrenal Cortex secretion is regulated by ACTH from the Anterior Pituitary-ACTH: (Adrenocorticotropin Hormone) CRH stimulates Corticotropin cells in Anterior Pituitary to secrete ACTH->released into blood->goes to Adrenal Cortex, binds to GPCR cell surface receptors (with cAMP second messenger) to stimulate secretion in Adrenal Cortex.-Aldosterone (mineralocorticoid): Binds to Nuclear receptors in cells of the Collecting Tubule portion of Nephrons. A “mineralocorticoid, produced in Zona Glomerulosa of Adrenal Cortex. Is controlled by ACTH but is also regulated by K+ in the Renin-Angiotensin System. >Renin-Angiotensin-Aldosterone System: activates when blood pressure, blood volume or Na+ level is low → stimulates _________ secretion → Renin converts Angiotensin (Ag) into ___________________ → Then _____________________________ secreted from the lungs converts Ag1 into Ag2 (Angiotensin 2) → Ag2 acts as a vasoconstrictor and stimulates the production of Aldosterone from __________________ in the _________________ of the Adrenal Cortex → Aldosterone is carried by the blood to the Nephron and binds to its receptor on the _________________ and _________________ → stimulates Peritubular capillaries to reabsorb _______ and ______, absorb HCO3-, and excrete ____ and ____ into the urine. In this way Aldosterone increases _________________ and Na+ blood concentration.-Excessive amounts of K+ in the blood (Hyperkalemia) increase Aldosterone secretion, and Aldosterone then increases K+ secretion into the urine to regulate its level in the blood. -Cortisol (glucocorticoids): The “stress” hormone produced in the Zona Fasciculata of the Adrenal Cortex. Maintains blood glucose, decreases glucose uptake, metabolism, suppresses inflammation, breaks down proteins (Proteolysis) and increases protein catabolism, increases Lipolysis (lipid break down), suppresses immune system, stimulates appetite, stimulates gluconeogenesis. Binds to Nuclear receptors of target cells. -Androgen: produced in the Zona Reticulata of the Adrenal Cortex. Binds to Nuclear receptors on target cells. Is a “male” sex hormone, though it is present in females to kickstart puberty. In puberty it causes _________&_________ hair growth and ______.-Adrenal medulla--Secretes Catecholamines: __________________________ and ______________________________ -Adrenal Medulla is NOT under the control of the Pituitary gland or Hypothalamus. (Neither are Pancreas or Parathyroid) -The Adrenal Medulla is derived from embryonic _____________ tissue (which is neural and gives rise to the CNS and PNS as well)-Noradrenaline & Adrenaline have receptors in the _______ for controlling Gluconeogenesis and Glycogenesis.-Norepinephrine: is produced by _____________ cells in the Adrenal Medulla, CNS, and in Peripheral Sympathetic nerves. These hormones also act as neurotransmitters. It controls smooth muscles (including the smooth muscles layer around blood vessels and the viscera lining of organs) in the GI, Respiratory System, Sweat glands, and Heart. Heart activity, heart rate, conduction velocity, and contractility are all influenced by Norepineprine as well. -Effects of Norepinephrine depend on the type of receptor it binds to: >___: vasoconstriction, contraction of smooth muscles (including sphincters), blood pressure increases >___: relaxation of smooth muscle, dilation of sphincter, vasodilation >___: increased heart rate, myocardial contractions, and conduction velocity. Propranolol and Atenolol are ______________ (β-blockers). >___: Relaxes bronchi. Albuterol is an __________ for Norepinephrine at this receptor-Epinephrine: is produced by ____________ cells in the Adrenal Medulla. Controls blood pressure, Controls glucose formation and absorption in liver-Adrenaline and Noradrenaline Synthesis:-Precursor amino acid ___________ is catalyzed by the enzyme ____________________ to become ____________________________, which is catalyzed by the enzyme _____________________ to become _______________, which is catalyzed by enzyme _______________________ to become Norepinephrine, which can be catalyzed by enzyme ________________________________________ to become Epinephrine-Thyroid gland--The located alongside the Hyoid bone and the 1st ring of the Trachea in the throat. -Has 2 lobes (Left & Right). -The blood supply to the Thyroid gland is important and brings Iodide (I-), a precursor for hormones (T3 & T4). -Blood from the ___________________ (a branch of the Thyrocervical trunk, which comes from the Subclavian artery) supplies the Inferior lobe of the Thyroid gland. -Blood from the ____________________ (a branch of the External Carotid artery, which comes from the Common Carotid artery) supplies the Superior lobe of the Thyroid gland. -Venous blood drains from the Thyroid gland into the ___________________________ → to the Internal Jugular vein in the neck → to the Brachiocephalic vein → then into the Superior Vena Cava. -Thyroid nerve supply is controlled by the ______________ Nervous System (Parasympathetic & Sympathetic).-The Thyroid gland derives from embryonic _________________ tissue. -Internal Structure: The Thyroid gland has a single layer of ___________, which have receptors for TSH on the basolateral surface of the cells, which faces the bloodstream. Inside the follicular lumen is “colloid” fluid which contains ___________________ (containing ____________ amino acids) which act as a precursor for T3 and T4 production.-Thyroid Hormones--The thyroid gland produces two hormones: ________________ (T4) and ____________________ (T3)-In the circulatory system, ~99.9% of all T4 and ~99.5% of all T3 in the blood are bound to plasma carrier proteins, most commonly _____________________________, to inhibit Renal excretion into the urine.-When TSH binds to _______ receptors on the basolateral-surface of follicular cells it activates _____________________, then _______ Second Messenger, causing the apical surface of the cell to reabsorb Thyroglobulin to begin synthesis of Thyroid Hormones T3 and T4.-T3 and T4 bind to ____________ receptors in their target cells and are critical in cell differentiation during development, and help in maintaining thermoregulation and metabolic homeostasis in the body. -Synthesis of Thyroid Hormones-1 – Na+/I- symport pump transports iodide into follicle cells:-After TSH binds to its receptor on the follicle cell membrane, it activates the cells to uptake ___________ and iodide, which symports into the cell along with sodium. 2 – Iodide Oxidation: Iodide (I-) is catalyzed by Peroxidase enzyme to oxidize into _________, which is now reactive and ready to form the inactive forms of T3 and T4 by the process of “________________”.3 – Organification combines Iodine molecules with Tyrosine residues from Thyroglobulin:-when __ molecule of Iodine (I2) and __ molecule of Tyrosine combine, they form Monoiodotyrosine (MIT). -when __ molecules of Iodine (I2) and __ molecule of Tyrosine combine, they form Diiodotyrosine (DIT).4 – Coupling makes combinations of MIT and DIT to form T3 and T4:-While MIT and DIT are attached to the Tyrosine residues of Thyroglobulin, two coupling reactions occur:> >-These reactions are catalyzed by Peroxidase enzyme, and result in the active forms of thyroid hormones.-More T4 than T3 is synthesized in this process, although T3 is more potent and active in bodily mechanisms.-T4 can be modified into T3 at the site of target tissue.-Thyroid Hormone Physiological function: -T3 and T4 are both active independent of each other but can collaborate in function.-T4 can pass through Placenta membrane and converts to T3 to control the development of the _____, _____, and ____________ in the fetus. >More specifically, T3 is synergistic with ____ and ______________ hormones for fetal bone formation-In adults, Thyroid hormones control memory, learning, body metabolism and temperature, increases O2 consumption in different cells (except in the Brain, Spleen, and gonads), increases glucose absorption from the GI, controls glucose metabolism, gluconeogenesis & glycogenolysis in the Liver, increases Lipolysis and Proteolysis, increases sensitivity to ____ and ____ sympathetic receptors, increase ventilation rate, control heart rate, contractility of myocardium, and blood pressure.-Parathyroid glands--Glands consist of 4 pea-sized lobes located posterior to the Thyroid Gland-Uses a cell-surface ______ and ______ as a Second Messenger-They are sensitive to Phosphorus and Ca2+ levels in the blood (____ mg/dL is the normal Ca2+ value)-_________ secrete Parathyroid Hormone (PTH), which regulates blood levels of Ca2+ and Phosphorus >If PTH increases one the other will decrease-PTH secretion is controlled by a __________ feedback loop, high levels of Ca2+ will __________ PTH secretion-PTH binds to receptors on bone (________________) to remove Phosphate and Ca2+ from the bone and release it into the Extracellular fluid. This does not directly translate to increased serum levels of Ca2+ because the Phosphate will associate with Ca2+. By inhibiting Phosphate reabsorption in the _________________ of the Nephrons in the Renal System, Phosphates can be excreted into the urine in larger amounts (Phosphaturia), causing Phosphate to dissociate from Ca2+ to replace what was lost, then Ca2+ can enter blood serum to increase Ca2+ levels. -PTH receptors on the __________________ of Nephrons results in Ca2+ reabsorption directly to the blood.-PTH also has receptors on the Epithelial cells of the small intestine and binds to increase Ca2+ absorption from Chyme in the small intestine.-Slight decreases in Mg2+ increase PTH secretion, but deficiencies in Mg2+ inhibit PTH secretion, which can lead to _____________________ and _____________________.-PTH has receptors in the _______________ of Nephron and binds to convert the inactive form of __________ (_____________________) into its active form (1,25-dihydroxycholecalciferol), which is then absorbed into the Peritubular capillaries. This process can generate ________ for intracellular energy, which is then expelled as waste into the urine.-The vitamin D then travels to the GI to assist with Ca2+ absorption from epithelial cells in the small intestine.-Deficiency of PTH causes a deficiency of vitamin D, which causes a deficiency of Ca2+ and ________________.-_________________________ also causes Osteoporosis since excess PTH removes too much Ca2+ from the bones, weakening them. -The Importance of Calcium in the Body--Calcium is important for muscular contractions and is seen in large amounts in the mechanism of the ______________________________.-Calcium is used in large amounts in ________________ to regulate contractility of myocardium, and in contractions of the smooth muscle layer of blood vessels, __________________ of the GI tract, and smooth muscle layers of internal organs.-Calcium regulates action potentials of _____________ and ________________ node in the right atrium of the Heart, and we see in ____________, that excess Ca2+ ________ heart rate by stimulating the SA and AV nodes-Calcium (and vitamin D) are important for maintaining bone density and development.-Pancreas--The Pancreas is located between the second part of the Duodenum and the Spleen. It has both Exocrine and Endocrine function.-The Exocrine portion of the Pancreas has acini (acinar cells) which secrete digestive enzymes: >___________________, __________________, ___________________-The Endocrine portion of the Pancreas, called the _______________________ contains 4 major cell types:α-cells: located in the outer rim of islet, secrete _________________β-cells: located in the central part of the islet, secrete ______________ δ-cells: are found throughout the Pancreas and secrete __________________ and GastrinPP cells: produce less than 1% of Pancreatic polypeptide, which can act as Paracrine hormones (that act like Somatostatin)-________________________ link β-cells to β-cells, α-cells to α-cells, and β-cells to α-cells to facilitate more rapid cell to cell communication. -Pancreatic Endocrine Hormones--Glucagon (α-cells):-Glucagon secretion depends on blood level of glucose; low levels increase Glucagon secretion which increases blood glucose in response. Glucagon has cell-surface GPCR receptors in the Liver and in Adipose tissue that use Second Messenger _________ to stimulate the production of Glucose from stored Glycogen.-Glucagon is very efficient in small amounts, 1 g/kg of Glucagon elevates blood levels of Glucose by 20 mg/dl within 20 minutes.-Glucagon elevates blood glucose levels by increasing the rate of ___________________ (Glycogen → Glucose) and inhibiting __________________ (Glucose → Glycogen) in the Liver.-Glucagon also increases blood glucose by increasing ____________________ along with Cortisol. This process utilizes lactic acids, fatty acids, amino acids and glycerol to produce new glucose molecules. ______________ generates glycerol, fatty acids and ketoacids. ____________ generates amino acids from protein degradation, and any unused amino groups are dumped into urea (increasing urea production) for excretion in the urine.-Somatostatin (δ-cells): Down-regulates _____________ and ____________ by inhibiting their secretion, indirectly decreases peristalsis, indirectly decreases secretion and absorption in the GI tract by inhibiting Histamine and Gastrin action on G-cells, therefore inhibiting secretion in Parietal cells. Prolongs digestive window for nutrient assimilation from the small intestine into blood.-Insulin (β-cells):-Is increased when blood glucose levels are ________ to facilitate cellular uptake of glucose and decrease blood levels to normal (___________ mg/dl)-Insulin has receptors in most types of tissue but most importantly in the: ______, ________, & ____________-target cell uptake of glucose from blood facilitates the production of ATP-Hyperglycemia increases _________ secretion, while Hypoglycemia increases __________ secretion.-Hyperglycemia occurs when blood glucose exceeds 120 mg/dl - Insulin increases and Glucagon decreases-Hypoglycemia occurs when blood glucose drops below 50-60 mg/dl – Insulin decreases an Glucagon increases-When blood glucose is too high: >Insulin stimulates __________________ (Glucose → Glycogen) in the Liver >Insulin inhibits _____________________ (Glycogen → Glucose) and >Insulin decreases ______________________ by increasing levels of ________________________ by promoting _________________________ enzyme activity. >Insulin decreases Lipolysis and increases _____________, which decreases ______________ formation by decreasing the acetyl CoA by-product formed by Lipolysis. >Decreases blood levels of K+ by closing cell membrane K+ channels during Glucose uptake-Insulin Secretion Mechanism--Increased blood glucose above the normal range stimulates β-cells in the Pancreas to secrete Insulin by the following process: Glucose from the blood enters the β-cell through ________ channels in the membrane, causing some uptake of K+ from the blood followed by the closure of K+ channels. Increased K+ remains inside the cell and depolarizes it to open calcium channels for Ca2+ to enter the cell. As Ca2+ levels increase in the cytoplasm it causes the exocytosis of Insulin secretory vesicles out of the β-cell and into the blood. -Target Cell uptake of Insulin--Insulin binds to cell-surface receptors and activates the ________ molecule to insert itself into the cell membrane and act as a channel for Glucose transport. This allows Glucose to enter the target cell. Once inside the cell, Glucose is converted into ________________ during _____________ inside the cell, which can then enter the ______________ for ATP production. Energy generation from glucose and O2 is ________________________________. -Glycogenesis: creation of glycogen from glucose. Glucose->Liver->___________________________-> glucose-1-phosphate->Glycogen. _____________________ enzymes catalyze this process. Glucagon is secreted by Pancreatic alpha-cells and stimulates the Liver to inhibit this process.-Glycogenolysis: The reverse process, when the body needs more glucose, the Liver breaks down stored Glycogen back into Glucose. Glycogen->_____________________->glucose-6-phosphate->Glucose. Glucagon from Pancreatic alpha-cells stimulates Liver to begin this process.-Gluconeogenesis: Stimulated by Glucagon and _____________. The formation of glucose from fatty acid, lactic acid, glycerol, and amino acid in the Liver, which is carried to the muscle for use.-Pineal gland--Is located in posterior region of the 3rd ventricle of the brain and secretes _______________ to control sleep. -The absence of light stimulates melatonin secretion to induce sleep. -As you age, Pineal glands may atrophy or calcify, causing ___________________. >This can be treated with synthetic melatonin.-Melatonin Synthesis: ________________ precursor is a neurotransmitter that is derived from its precursor, _________________, an amino acid. Pineal cells install _________ functional groups (________________) and -CH3 groups (________________) onto Serotonin to convert it into Melatonin. This process is dependent on the amount of light exposure to the eyes, as abnormal light exposure inhibits this process and may result in sleep issues.-The effects of Light-Dark exposure: When the retina of the eye is exposed to _____________ amounts of light (like when the sun is setting) it stimulates a signal to activate the _________________ nucleus found in the __________________, which is an organ that regulates many biological processes including sleep and our natural Circadian rhythm. Nerve fibers extend down the spinal cord to transmit the activation signal to the ______________________________, which sends the signal back up the spinal cord along its post-ganglionic nerve fibers to innervate the Pineal Gland to begin hormone synthesis and secretion. -Prostaglandin--Prostaglandins bind to cell-surface ________ of target cells and use Second Messenger _________-Every cell has prostaglandin secretion, which can stimulate a wide variety of functions, including: >blood vessel >smooth muscle > > -Prostaglandin secretion increases: >During erections, where it vasodilates the dorsal vein in the penis. -Synthetic prostaglandin is used to treat Erectile Dysfunction. >During labor it dilates the cervix of the uterus >During menstruation it can irritate the pelvic cavity and cause pain-Prostaglandin-E2 can irritate the temperature center in the Hypothalamus and cause fever -Forms from the precursor _____________________ which is converted by _____________________ enzyme -Common types of Prostaglandins (PG):-_______: active in Antiplatelet aggregation (inhibits blood clotting) and vasodilation-_______: active in smooth muscle relaxation, vasodilation, and is the causative agent in fevers -_______: active in smooth muscle contractions and vasoconstriction >PGE2 and PGF2α both involved in uterine contractions during childbirth-__________________________: active in platelet aggregation (blood clotting) and vasoconstriction-Prostaglandin precursor Arachidonic acid can also be oxidized by _____________________ enzyme to form ____________________ inside specialized leukocytes. Leukotrienes are mostly active in __________ reactions to induce bronchial inflammation, bronchoconstriction and vasoconstriction in the Respiratory System. -Leukotrienes and specialized Prostaglandins are usually synthesized at the same time as they act ______________________ in Asthmatic ______________________ reactions.-Prostaglandin Inhibitors:-Certain drugs can inhibit Cyclooxygenase enzyme from being able to catalyze Prostaglandin synthesis, including _________________________________________ like Aspirin, Ibuprofen, Naproxen, and Indomethacin (preferred for babies with heart conditions)-Hormones of the Gonads and Placenta--Prolactin: prepares mammary gland for breast feeding-Precursors: for TSH, ACTH & GH secreted by Placenta-Growth factors: secreted by the Placenta, which are important for embryonic cell proliferation and growth-Relaxin: relaxes the Pelvic joints and prepares the pelvic cavity for pregnancy, relaxes cervix for delivery-Testosterone, Progesterone, and small amounts of Estrogen are also secreted by the Placenta-Estrogen- -Is secreted by the gonads once puberty begins, and from ________________ during pregnancy-Estrogen in excess can suppress __________________ and cause infertility in males-Estrogen is important in the development of genitalia in female fetus, for the development of the ovaries and the descent of ovaries from the abdominal cavity and into the pelvic cavity-Estrogen levels increase after menstruation for the regeneration of the Endometrium layer in the uterus.-Estrogen is important for the development of _________________________ including breast development, changes in body shape, and the accumulation of fat for the rounding of the hips and legs. -Estrogen deficiency can cause depression, anxiety, nervousness, and infertility. -Before and during menstruation Estrogen levels decrease and commonly causing feelings of depression. -Depression caused by Estrogen deficiency can occur in menopausal and post-menopausal people due to Estrogen levels decreasing significantly and permanently.-Progesterone--Important for preparing and maintaining the _______________ of the uterus for implanting a fertilized ovum. -Secretion is controlled by ______________ that develop into the Corpus Luteum in the ovary, during the ______ trimester of Pregnancy. -In the ________ & _______ trimester, the control of Progesterone secretion is taken over by the placenta. -Progesterone deficiency can cause ________________________________________. -Testosterone--LH stimulation of the _____________ in testicles induces Testosterone secretion-High levels of Testosterone can __________ LH secretion via ___________ feedback-A male sex hormone important in the development of testicles in the male fetus, and the descent of testicles from the abdominal cavity and into the scrotum during intrauterine life. -Controls the development and growth of genitalia after birth as well. -Dihydrotestosterone is another sex hormone complementary to Testosterone-Testosterone is important in the development and maintenance of Secondary Sex Characteristics during and after puberty, including muscle development, voice changes and increased libido -Controls production of sperm after puberty. -Testosterone deficiency can cause infertility and depression, since it controls mood to an extent (though emotions are also under the control of serotonin and dopamine neurotransmitters and the Limbic System) -Important for fluid absorption into the blood, in this way it has a hand in regulating blood volume -Testosterone can stimulate an increase in red blood cell production-Ovaries secrete small amounts of Testosterone since it is molecularly similar to Estrogen and can be converted into Estrogen via Aromatase enzyme. Adipose tissue can increase Aromatase levels, so obese males with Testosterone deficiencies may be infertile due to Aromatase catalyzed conversion into Estrogen. ................
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