Endo: Diversity Of Endocrine Hormones Flashcards
Hormones are chemical non-nutrient, intercellular messenger that is effective at micromolar concentrations or less (high efficiency)
Broader definition
Hormones are chemical substances produced by specialized tissues and secreted into blood, in which they are carried to target organs and triggers specific biologic functions. And by whom?
Classical definition. Starling and Bayliss
Communicates to adjacent tissue by local chemical release (neurotransmitter)
Nervous system
Communicates to distant tissues through blood-carried chemicals.
Endocrine system
Acts through chemical messengers(hormones) carried in the circulation by secretion into blood and extracellular fluid.
Endocrine system
Cell must bear a _______ for the secreted hormones to respond.
Receptor
Hormones can be classified according to
Chemical composition, Solubility properties, Location of receptors & Nature of signal used to mediate hormonal action
These are lipophilic, has transport proteins, long plasma half life (hours to days), mediated intracellularly and contains receptor hormone complex
Calcitriol, Retinoids, Iodothyronines & Steroids “CRIS”
These are hydrophobic, no transport proteins, short plasma half life (minutes), mediated by plasma membrane and receptors are cAMP, cGMP, Ca2+, metabolites of complex phosphomositols & kinase cascades
Polypeptides, Proteins, Glycoproteins & Catecholamines “PaPa GC”
Hormone synthesize in thyroid
Triiodothyronine
Hormones synthesized in Adrenal
Glucocorticoids, mineralocorticoids
Hormones synthesized in the Pituitary
FSH, LH, ACTH, GH, Prolactin & TSH “FLAG PT”
Hormone produced in specialized cells of the Small Intestine
Glucagon-like peptide
Hormone produced in specialized cells of the thyroid
Calcitonin
Hormone produced in specialized cells of the kidney
Angiotensin
Synthesis of some hormones requires the ___________ of more than one organ
Parenchymal cells
These organs are required for the production of 1,25(OH)2-D3 or calcitriol
Skin, liver & kidney
Hormones usually affects only _______. Responds to a hormone because it bears receptors.
Target cells
Hormones can change its target cells by. (Transmit the information gained from binding to the hormone into a cellular response)
Activation of enzymes & Modulation of gene expression “A.M”
Hormone is distributed in blood and binds to distant target cells
Endocrine
Hormone acts locally by diffusing from its source to target cells in the neighborhood
Paracrine
Hormone acts on the same cell that produced it
Autocrine
Secreted by cells in a locl area and influences the activity of the same cell from which it was secreted. Give an example.
Autocrine. Prostaglandin.
Produced by a wide variety of tissues and secreted into tissue spaces; has a localized effect on adjacent cells. Give an example.
Paracrine. Prostaglandin & Histamine.
Secreted in the blood by specialized cells; travels by the blood to target tissues. Give an example.
Hormone. Thyroxine & Insulin.
Produced by neurons and functions like hormones. Give an example.
Neurohormone. Oxytocin & ADH.
Produced by neurons and secreted into extracellular spaces by nerve terminals; travels short distances, influences postsynaptic cells or effector cells. Give an example.
Neurotransmitter. ACH & Nor Epi
Location of receptor. Generation of second messenger which alter the activity of other molecules usually enzymes within the cell. Water soluble. Ex: proteins & peptides, catecholamines & eicosanoids
Cell surface receptors (plasma membrane)
Location of receptor. Alter transcriptional activity of responsive genes. Lipid soluble. Ex: steroid & thyroid hormones
Intracellular receptors (cytoplasm, nucleus)
Number of domains of Integral membrane proteins
Three
A domain in which residues exposed to the outside of the cell interact with and bind the hormone (ligand-binding domain)
Extracellular domain
A domain in which hydrophobic stretches of amino acids in the
Iipid bilayer that anchor the receptor in the membrane
Transmembrane domain
A domain in which tails or loops of the receptor within the cytoplasm interact with other molecules to generate second messengers and transduction of the hormonal signal
Cytoplasmic/Intercellular domain
Do not enter the cell but bind to plasma membrane receptors, generating a chemical signal (second messenger) inside the target cell
Nonsteroid hormones
Activate other intracellular chemical to produce the target cell response
Second messenger
Examples of hormones which utilize Cyclic AMP
FSH, LH, ADH, Glucagon, Parathormone, Epi, Nor Epi, TSH, Calcitonin “FLAG PENT C”
Examples of hormones which utilize Protein kinase activity
Prolactin, Oxytocin, GH, Insulin, Erythropoietin “POGI E”
Examples of hormones which utilize Calcium and/or phosphoinositides
TSH, ADH, Nor Epi, Gonadotropin-releasing hormone & Epinephrine “TANGE”
Examples of hormones which utilize Cyclic GMP
Atrial Natriuretic Peptide & Nitric Oxide “NA”
Is a nucleotide generated from ATP through the action of ___________.
Cyclic AMP. Adenylate cyclase.
Elevated concentation of cAMP causes activation of a cAMP-dependent protein kinase called
Protein kinase A
Protein kinase A(inactive) becomes active when it binds ________. Upon activation, protein kinase A _________ other proteins which alter the cell’s state. Give an example.
cAMP. Phosphorylates. Glucagon.
Tyrosine kinase second messenger system example
Insulin
Composed of single polypeptide chain with three distinct domains
Steroid and thyroid hormones
A steroid & thyroid hormone receptor domain in which amino acids in this region are responsible for binding of the receptor to specific sequences of DNA
DNA binding domain
A steroid & thyroid hormone receptor domain in which it is the region that binds hormone
Carboxy-terminus/ ligand-binding domain
Composition of hormones are mostly
Polypeptides & Glycoproteins
Adrenal hormones are synthesized from
Cholesterol
Catecholamine hormones are derived from _______. Give examples
Tyrosine. Thyroid & Adrenal medullary hormones.
General steps in hormone response mechanism
Hormone receptor protein, effector enzymes, second messenger & metabolic response triggered “HES-M”
Binds to the plasma membrane at specific site. Receptor protein changes shape and activates the G protein.
cAMP: Hormone receptor
Binds to the plasma membrane at specific site. Receptor protein changes shape and activates the G protein. G protein binds with GTP “replacing” GDP.
PIP- Calcium: hormone receptor
Effector enzyme of cAMP. G protein complex activates _______ which breaks GTP to _____. Generates second messenger cAMP from ______.
Adenylate cyclase. GDP. ATP.
Effector enzyme of PIP Calcium. G protein-GTP complex actives ________ which breaks _____ to GDP. PIP2(phosphatyidyl inositol biphosphate) into ______ & ______.
Phospholipase. GDP. Diacyglycerol & IP3 (Inositol triphosphate)
Second messenger of PIP Calcium. _______ activates protein kinase. _______ releases Ca+. Third messenger: _______ activates enzymes.
Diacyglycerol. IP3. Ca+.
Can also be found in the heart, pancreas, GIT & Fat stores.
Peptides & Proteins
______ cannot cross the cell membrane. Amino acid hormones bind with a protein _______ of the cell membrane.
Amino acids. Outside.
Examples of amino acid derivatives
Tyrosine, Tryptophan & Glutamic acid
Examples of steroid hormones
Cholesterol, Cortisol, Pregnelone & Testosterone “CCPT”
Examples of fatty acid derivatives
Prostaglandin, Prostacyclin, Leukotrienes & Thromboxanes “PPLT”
Effects of hormones depend largely on their concentration in blood and ECF: feedback loops. Rapid onset of peptide hormones and catecholamine. Rapid clearance of unbound hormones.
Rate of Production, Delivery & Elimination/Degradation
Is located in the middle base of the brain, encapsulates the ventral portion of ________.
Hypothalamus. 3rd ventricle.
Controls the release of pituitary hormones in a pulsatile manner
Hypothalamus
A 44-amino acid peptide hormone in the arcuate nucleus of the hypothalamus. Carried by the hypothalamic hypophyseal portal circulation to the anterior pituitary gland. Stimulates Growth hormone secretion.
Growth Hormone Releasing Hormone
Other name for GHRH
Somatocrinin
Released from the periventricular somatostatin neurons. Opposes GH. Inhibits GH secretion by hyperpolarizing _______.
Growth hormone inhibiting hormones. Somatotropes.
Other name for GHIH
Somatostatin
Height enhancer ingredient. Is high protein, calcium plus other minerals, Vit. ADEK, vitamins in the B group, Vit. K & Vit. C
Alfalfa
Height enhancer ingredient. Is very high in protein. Contains around 28% protein and has more protein that can be found in most meat products.
Wheat germ
Height enhancer ingredient. Flavoring agent.
Citric acid
Height enhancer ingredient. Used as an alternative treatment for arthritis and osteoporosis.
Hydrolyzed collagen
Height enhancer ingredient. Is used as a preservative because it works very well at killing bacteria, yeast and fungi.
Sodium Benzoate
Height enhancer ingredient. Involved in bone health.
Vitamin D3
Height enhancer ingredient. Used to prevent and treat calcium deficiencies.
Calcium Citrate
Height enhancer ingredient. For stronger bones.
Algae Calcium
Height enhancer ingredient. Is most commonly used as an antacid and also to treat calcium deficiencies.
Calcium Lactate
Height enhancer ingredient. Help to rebuild cartilage and treat arthritis.
Glucosamine
Height enhancer ingredient. Treats osteoporosis.
Copper Gluconate
Height enhancer ingredient. Can be applied in the food and beverage product which aim to enhance mineral absorption in the consumer. It facilitates calcium solubility, suggesting that overall digestive calcium uptake is improved.
Casein Phosphopeptide “CPP”
Height enhancer ingredient. Rich in nucleic acids, which are instrumental in natural human growth and are found in mother’s milk. Supplementation of infants with this product boost growth, development and vitality.
Chorella Growth Factor
Has 2 active forms produced by alternative cleavage of a single preproprotein: one of ___ AA and other of ___ AA. Secreted by hypthalamus, delta cells of stomach, intestine and pancreas.
Somatostatin
Mimics natural somatostatin pharmacologically. More potent inhibitor of GH, glucagon and insulin than the natural hormone.
Octreotide
Imhibit the release of GH, TSH and supress the release of GI hormones
Somatostatin
Lowers the rate of gastric emptying and reduces smooth muscle contractions and blood flow within intestine. Supress the release of pancreatic hormones and exocrine secretory action of pancreas.
Somatostatin
A polypeptide hormone and neurotransmitter involved in the stress response.
Corticotropin Releasing Hormone
Other name of CRH
Corticotropin-releasing factor/corticoliberin
CRH is synthesized by the _______ and seems to determine duration of ________.
Placenta. Pregnancy.
CRH stimulates ______ to secrete _______ and other biologically active substances (B endorphin)
Corticotropes. Corticotropin (ACTH)
Tripeptide hormone that stimulates the release of TSH and prolactin anterior pituitaryl
Thyrotropin releasing hormone (TRH)
Other name of Thyrotropin releasing hormone (TRH)
Thyroliberin/protirelin
______ is produced by the hypothalamus and travels acrossthe median eminence to the pituitary via the ___________.
TRH. hypophyseal portal system
A peptide hormone responsible for the release of FSH and LH from the anterior pituitary. Previously called as LHRH
Gonadotropin Releasing Hormone 1
The gene, GNRH1, for the GNRH1 precursor is located in chromosome __
8
GNRH precursor contains __ AA and is processed by GNRH1’ a decapeptide(10 AA) in mammals.
92
Considered as a neurohormone, a hormone that produced in a specific neural cell and released at its neutral terminal
GNRH1
What part of hypothalamus contains most of the GNRH1-secreting neurons
Preoptic area
How is GNRH1 degraded? Duration?
Proteolysis. Few minutes.
GNRH1 is secreted in pulses at a _______ frequency in males.
Constant
In females, the frequency of of the pulses varies during the ___________ and there is a large surge of GNRH1 just ___________.
Menstrual cycle. Before ovulation.
When does GNRH1 activity low?
Childhood
When does GNRH1 activity activated?
Puberty
During reproductive years, _________ is critical for successful reproductive function as controlled by _________.
Pulse activity. Feedback loops.
Once pregnancy is established? Is GNRH1 activity required?
No
Function as a neurotransmitter and neurohormone. Inhibit prolactin release.
Dopamine
Chemical name of Dopamine
4-(2-aminoethyl)benzene-1,2-diol “DA”
A subclass of the pituitary acidophilic cells
Somatotropes
Synthesized by somatotropes.
Growth hormone
Genes for human GH are localized in the ______ region of chromosome _____.
q22-24. 17.
Promotes GH secretion
GHRH & Ghrelin
Causes inhibition of GHRH
Somatostatin
Other name of GH
Somatropin/Somatotropin
GH receptor is a member of the _________ superfamily. GH is bound to a __________ derived from the GH receptor.
Cytokine receptor. growth hormone binding protein.
One growth hormone molecule binds to one receptor to form a ______ through which signaling occurs.
Dimer
A hormone homologous to proinsulin.
Insulin-like growth factor/Somatomedin C
Height growth in childhood is stimulated by what mechanisms
- Directly stimulates chondrocytes of cartilage
- Stimulates IGF1
Stimulators of GH
Hypoglycemia, Exercise, Estradiol & Dietary Protein “HEED”
Inhibitors of GH
Dietary Carbohydrate & Glucocorticoids “D&G”
Effects of GH: _______ liver glycogen.
Increases
Effects of GH: ______ transport of AA into muscle cells and also ______ protein synthesis.
Increase. Increases.
Effects of GH: antagonizes the effect of _______.
Insulin
Effects of GH: decreased peripheral utilization of ________.
Glucose
Effects of GH: ________ hepatic glucose production via ________.
Increases. Gluconeogenesis.
Effects of GH: promotes the release of ________ and _________ from adipose tissue.
FFA & Glycerol.
Effects of GH: promotes a positive ______, ______ & ______ balance.
Calcium, magnesium & phosphate.
Effects of GH: causes retention of ______, ______ & _______ ions.
Sodium, potassium & chloride.
Effects of GH: promotes growth of ______ bones.
Long
Effects of GH: stimulates ______.
Lactogenesis
Lack the ability to synthesize or secrete GH
GH-deficient dwarfs
Lack the IGF-1 response to GH but not its metabolic effects; thus the deficiency is post-receptor in nature.
Pygmies
Have normal or excess plasma GH, but lack liver GH receptors and have low levels of circulating IGF-1.
Laron dwarfs
Excessive amounts of GH before epiphyseal closure of the long bones leads to
Gigantism
Excessive GH after epiphyseal closure, acral bone growth leads to the characteristic features of
Acromegaly
Peptide hormone synthesized and secreted by lactotrope cells in the anterior pituitary gland
Prolactin
In prolactin, the molecule is folded due to the activity of _________.
Three disulfide bonds
Encoded by a gene on chromosome __ interacts with the prolactin molecule as a transmembrane receptor.
Prolactin receptor. 5.
The prolactin receptor, a member of the ______________ superfamily, is expressed in the immune system.
Hematopoietin/cytokine receptor
Synthesize and secrete biologically active prolactin, act as an autocrine or paracrine factor to modulate the activities of cells of the immune system.
Lymphocytes
Inhibits prolactin secretion when then causes regulation of its pituitary secretion.
Dopamine neurons
Stimulate the mammary glands to produce milk
Prolactin
High levels of this during pregnancy act directly on the breast to stop ejection of milk. When the levels of this hormone fall after childbirth, milk ejection is possible.
Progesterone
Indicator for the amount of sexual satisfaction and relaxation
Refractory period
Responsible for sexual arousal, causing the male’s refractory period.
Prolactin
Unusual high amounts of prolactin are suspected to be responsible for
Impotence & Loss of Libido
In women, Tumors of prolactin-secreting cells cause
Amenorrhea & Galactorrhea
In men, excess PRL is associated with
Gynecomastia and Impotence
A polypeptide placental hormone. Structure and function is similar to that of human GH. It is an anti-insulin. No definite function in humans.
Chorionic Somatomamatropin(CS) or Human Placental Lactogen(HPL)
An (a:B) heterodimer, with the alpha subunit being identical in all members of the family. The biological activity of the hormone determined by the B-subunit, not active in the absence of a-subunit.
Glycoprotein hormones
Glycoprotein family transduce their intracellular effects via what receptors
G-protein, Adenylate cyclase & Second-messenger system. “GAS”
Responsible for gametogenesis and steroidogenesis in the gonads
Gonadotropins
Stimulates the growth of Graffian follicles to maturation
FSH
Shuts off the FSH production. It is released as follicle grows
Inhibin
Controls FSH release
GnRH
Enhances FSH release
Activin
In men, FSH enhances the production of androgen-binding protein by the _______ cells of the testes and is critical for _______.
Sertoli. Spermatogenesis.
Act synergistically in reproduction
FSH & LH
FSH: alpha subunit is located on chromosome __. Beta subunit is on chromosome __.
- 11.
The sugar part of FSH is composed of ______, ______, ______, _____, _______ & _______, the latter being critical for its biologic half life of _____.
Fructose, Mannose, Glucosamine, Galactose, Galactosamine & Sialic acid. “FMGs”. 3-4 hours.
High FSH levels are typical in
Menopause
Diminished secretion of FSH can result in failure of gonadal function known as
Hypogonadism
Synthesized and secreted by gonadotropes in the anterior lobe of pituitary gland. Necessary for proper reproductive function.
Luteinizing Hormone
In females, acute rise of LH- the LH surge- triggers
Ovulation
In males, LH also called ________, stimulates ________ cell production of testosterone.
Interstitial Cell Stimulating Hormone(ICSH). Leydig.
Confers its specific biologic action and is responsible for interaction with the LH receptor
LH beta subunit
LH has a beta subunit of ___ AA. Alpha subunit is same as ____.
- FSH.
LH beta subunit contains the same AA in sequence as beta subunit of _____ and both stimulate the same receptor. However, the HCG beta subunit contain additional ___ AA, and both hormones differ in composition of their sugar moieties. The different composition of these oligosaccharides affect _____ & _________.
HCG. 24. Bioactivity & Speed of degradation.
LH: beta-subunit is localized in the LHB/CGB gene cluster on chromosome __.
19.
_____, ______ & ________ do not affect genetic activity for the beta subunit production of LH.
Activin, inhibin & sex hormones
In women, LH levels are normally low during _____ and high after ______
Childhood. Menopause.
The detection of this has become useful for people who want to know when ovulation occurs.
LH surge
Diminished secretion of LH result in failure of gonadal function known as. Manifest in males as failure in production of normal number of _____. In females, ______
Hypogonadism. Sperm. Amenorrhea.
Peptide hormone that is produced in pregnancy, that is made by the embryo soon after conception and later by _________.
Human Chorionic Gonadotropin. Syncytiotrophoblast.
Prevent the disintegration of corpus luteum & maintain progesterone production. Affects the immune tolerance of the the pregnancy. Used for early pregnancy testing.
HCG
Heterodimeric, with an A-subunit identical to that of LH, FSh and TSH and B-subunit that is unique to which.
HCG
Encoded by ___ homologous genes which are arranged in tandem an inverted pairs of chromosome __.
BhCG. 6. 19.
Extensively used as a parenteral medication in fertility therapy in lieu of LH. ____ is also secreted by cancers including teratomas, choriocarcinomas and islet cell tumors.
HCG. BhCG.
In males, hCG injections are used to stimulate _____ cells to synthesize ______.
Leydig. Testosterone.
Mimics LH and helps restore and maintain testosterone production in the testes. It is also used in combination with various __________ cycles.
hCG. Anabolic Androgen Steroid.
Synthesized and secreted by thyrotrope cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland. Also known as
Thyroid Stimulating Hormone. Thyrotropin.
TSH secrete
Thyroxine(T3) & Triiodothyronine(T4)
TSH production is controlled by ____, from the hypothalamus and transported to the pituitary gland, where it increases TSH production and release.
Thyrotropin Releasing Hormone
Decrease TSH
Somatostatin
When the levels of T3 and T4 are low, the production of TSH is ____. And in vice versa TSH production is ____. Creates a regulatory negative feedback loop.
High. Low.
TSH receptor is found where
Thyroid follicular cells
Stimulation of TSH receptor
Increases T3 & T4 production and secretion.
Stimulating antibodies against TSH receptor _____ TSh action and are found in what disease
Mimic. Graves’ disease.
TSH: alpha chain is located on chromosome __. Beta chain is located on chromosome __.
- 1.
Excess TSH levels
Hyperthyroidism
Deficient TSH levels
Hypothyroidism
Expressed in both the anterior and intermediate lobes of the pituitary gland. The primary protein product of this gene is a ___ AA precursor- undergo differential processing to yield atleast __ peptides, dependent upon the location of synthesis and the stimulus leading to their production.
Proopiomelanocortin(POMC) gene. 285. 8.
Secreted from the corticotropes in the anterior of the pituitary gland in response to the hormone Corticotropin-Releasing Hormone(CRH) by the hypothalamus.
ACTH
ACTH consists of __ AA, the first 13 if which (counting from the N-terminus) may be cleaved to form _____. Half life of ACTH in human blood is about ____.
- a-MSH. 10mins.
Stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids. Acts through stimulation of cell surface ACTH receptors located on the adrenocortical cells. Also related to circadian rhythm in many organisms
ACTH
Enumerate the corticosteroids
Glucocorticoids, mineralocorticoids, sex steroids(androgens)
Hormones that are also released together with ACTH
Lipotropin, B-endorphin, Met-enkephalin & Melanocyte Stimulating Hormone “LBMM”
Excessive ACTH production results in what disease state and its causes
Cushing syndrome. (-) N, K & P balance, Na retention, Glucose intolerance, Inc plasma fatty acids and Dec circulating eosinophils & lymphocytes.
Causes lypolysis and fatty acid mobilization, but its physiologic role is minimal.
B-Lipotropin
Binds to CNS receptors like opiates and may play a role in pain perception, appetite & immune response
Endorphins
Stimulates darkening of skin
Melanocyte-Stimulating Hormone
Posterior pituitary hormones. Synthesized as prohormones in neural cell bodies of the hypothalamus. Axons terminate in the posterior pituitary, and the hormones are secreted directly into the systemic circulation
Oxytocin & Vasopressin
Hormone that is mainly released when the body is low on water. It causes the kidneys to conserve water by concentrating the urine and reducing urine volume.
Arginine vasopressin(AVP)/ADH/Argipressin
A peptide hormone liberated from a preprohormone precursor that is synthesized in the hypothalamus. Secreted in response to reductions in plasma volume and increases in plasma osmolality. And in response to increase plasma osmotic pressure mediated by osmoreceptors in the hypothalamus.
Vasopressin
Pressure receptors that activate ADH secretion
Veins, Atria & Carotid “VAC”
Reduces vasopressin secretion
Ethanol & Caffeine
The resulting decrease in water reabsorption by the kidney leads to
Higher urine output
Stimulates secretion of ADH
Angiotensin II
Vasopressin acts on how many receptors
Three
ADH receptor: Corticotropin secretion from the pituitary gland
V1b
ADH receptor: control of free water reabsorption in the collecting ducts of the kidneys(especially the cortical and outer medullary collecting ducts)
V2
ADH receptor: vasoconstriction, gluconeogenesis in the liver, platelet aggregation and release of factor. VIII and von Willebrand factor
V1a
In ADH, activation of _________ causes increase cAMP which leads to the insertion of _______ channels (water channels) into the apical membrane of the cells lining the collecting duct.
Adenylate cyclase. AQP2.
ADH is a peptide that contain ___ AA. AA sequence of arginine vasopressin, with the cysteine residues from a ________.
- Sulfur bridge.
Has a lysine in place of arginine.
Lysine Vasopressin
Decreased ADH release or decreased renal sensitivity to vasopressin leads to a condition featuring hypernatremia, polyuria & polydipsia.
Diabetes Insipidus
High levels of ADH secretion and resultant is hyponatremia occurs in brain diseases and condition of lungs.
SIADH
is a mammalian hormone that also acts as a neurotransmitter in the brain. In women, it is released mainly after distention of the cervix and vagina during labor, and after stimulation of nipples, facilitating birth and breastfeeding.
Oxytocin
Oxytocin is released during ______ of both sexes. In the brain, oxytocin is involved in ______ & ______, and might be involved in the formation of ______ between people.
Orgasm. Social recognition & Bonding. Trust.
Oxytocin is a peptide of __ AA. The cysteine residues form a _______. It has a molecular mass of _____ daltons.
- Sulfur bridge. 1007.
Expresses oxytocin receptors, and in both the myometrium and endometrium of the uterus at the end of pregnancy.
Myoepithelial cells of mammary gland
Due to its similarity to ADH, it can reduce the excretion of urine slightly.
Oxytocin
Thyroid hormones requires this trace element for biologic activity
Iodine
Is the precursor of T4 and T3. Produced on RER, has a molecular weight of 660,000. It is glycosylated and contains more than 100 tyrosine residues, which become iodinated.
Thyroglobulin
Steps in TH synthesis: A ___________ concentrates iodide in thyroid cells, and the iodide is transported to the _________. It is oxidized by a ________ found only in thyroid tissue.
Na/K ATPase driven pump. Follicle lumen. Thyroperoxidase.
Steps in TH synthesis: the addition of oxidized iodide to tyrosine residues of thyroglobulin is catalyzed the same thyroperoxidase enzyme, leading to production of
Thyroglobulin Monoiodotyrosyl(MIT) & Diiodotyrosyl(DIT) “organification”
Steps in TH synthesis: process in which thyronines, T3 & T4, are formed by combining MIT and DIT residues on thyroglobulin.
Coupling
The only tissue that can oxidize to a higher valence state, an obligatory step in organification and thyroid hormone biosynthesis.
Thyroid
Steps in TH synthesis: mature, iodinated thyroglobulin is taken up in vesicle by ______ and fuses with ______.
Thyrocytes. Lysosomes.
Steps in TH synthesis: degrade thyroglobulin releasing AA and T3 & T4, which are secreted into the circulation.
Lysosomal protease
T3 & T4 are very ______ and require a carrier protein for delivery to target tissues. In the plasma, T3 & T4 are bound to a carrier glycoprotein known as _________ and are disseminated throughout the body in this form.
Hydrophobic. Thyroxin-binding globulin.
Thyroid hormone circulating in the blood is bound to transport proteins
Thyroxine-binding globulin(70%), Thyroxine-binding prealbumin(10-15%) and Albumin(15-20%)
Protein that is responsible for the transport of retinol-transthyretin
Thyroxine-binding prealbumin
Responsible for the biologic activity.
Unbound thyroid hormones
Binds to the thyroid receptor in target cells 10x more than T4, so more metabolically active. However T4 has 5x half life than this.
T3
Selectively removes iodidefrom the 5’ position of T4 to make it T3. Found in target tissues such as pituitary, kidney and liver.
Peripheral deiodinase
Inhibits the conversion of T4 to T3
Propylthiouracil & Propanolol.
Increases BMR, protein synthesis, body’s sensitivity to catecholamines and regulate protein, fat and carbohydrate metabolism.
Thyroid hormones
In the embryo, this is necessary for normal development
Thyroid hormones
Hypothyroidism in embryo is responsible for this which is characterized by multiple congenital defects and mental retardation
Cretinism
Increase cardiac output, heart rate, ventilation rate & BMR. And for development of brain and thickens endometrium.m
Thyroxine
Activate the human thyroid TSH receptor, leading to the hyperthyroidism of Grave’s diseases. Bind to TSH receptor and mimic the TSH stimulation of the gland by increasing intracellular cAMP.
Thyroid Stimulating Autoantibodies
Enlargement of thyroid
Goiter
Insufficient T3 or T4 results to this causing slow heart rate, diastolic HPN,sluggishness,constipation,cold intolerance and dry skin.
Hypothyroidism
Excess thyroid hormone results to this which has opposite symptoms to hypothyroidism
Thyrotoxicosis
Leads to the ff manifestations: inc metabolic rate,weight loss,negative nitrogen balance,excessive sweating,palpitations,dyspnea,tremor,weakness,exophthalmos and goiter.
Hyperthyroidism
Leads to the ff manifestations: dec metabolic rate,weight gain,positive nitrogen balance,cold sensitivity,dec cardiac output,hypoventilation,lethargy,mental slowness,drooping eyelids,growth & mental retardation and goiter
Hypothyroidism
There is approximately 1kg of Ca in the body, 99% of which is in bone where it forms
Hydroxyapatite crystals with phosphates
Not complexed with organic acids or bound to proteins, is the biologically active fraction of calcium
Ionized calcium
Low ionized calcium levels causes
Tetanic convulsions
Elevated calcium causes
Muscle paralysis & Coma
Binds calcium and may alter circulating calcium levels
Albumin
Synthesized and secreted by chief cells of the parathyroid in response to systemic Ca2+ levels. MW is 9500 and is secreted as an __ AA peptide.
Parathyroid Hormone. 84.
Immediate precursor of PTH which differs from the native 85-amino acid hormone by having a highly basic hexapeptide amino termianl extension
ProPTH
The primary gene product and the immediate precursor of proPTH is the _______. This differs from proPTH by having an additional __ AA terminal extension that is ______.
115-AA preproPTH. 25. Hydrophobic.
PTH 1-34 has a full biologic activity, and the region _____ is primarili responsible for receptor binding.
25-34
An acute decrease of calcium results in marked
Increase of PTH mRNA
Regulates Ca2+ concentration in extracellular fluids. Acts by binding to cAMP-coupled plasma membrane receptors. Increases Ca2+ levels in extracellular fluids.
PTH
Induces the dissolution of bone by stimulating osteoclast activity, which leads to elevated plasma Ca2+ and phosphate
PTH
In the kidney, PTH _____ renal Ca2+ clearance by stimulating its reabsorption. At the same time PTH reduces the reabsorption of phosphate and thereby ______ its excretion in the kidneys.
Reduces. Increases.
Acts on the skin, liver and kidney to stimulate production of calcitriol or Vit. D which is responsible for Calcium absorption in the intestine
PTH
Results in muscle cramps and tetany. It usually due to accidental removal of the parathyroid gland during neck surgery.
Hypoparathyroidism
PTH is produced but there is end-organ resistance to its effects
Pseudohypoparathyroidism
Is usually due to cancer causing high ionized calcium and low serum phosphate levels
Hyperparathyroidism
May be seen in patients with progressive renal failure due to inefficient calcium reabsorption caused by decreased activity of Vitamin D which is not activated by the kidney.
Secondary hyperparathyroidism
The only hormone that can promote the translocation of calcium against concentration gradient which exists across the intestinal cell membrane.
Vitamin D
Deficient bone mineralization. Deficiency of Vit. D in children causes
Rickets
Deficient bone mineralization. Deficiency of Vit. D in adult causes
Osteomalacia
Is normally found in persons sufficient with sunlight
Vit. D
Most potent naturally occurring metabolite of Vit. D
Calcitriol
In the skin, Vit. D is produced from ________ during photolysis reaction
7-Dehydrocholesterol
In the liver, Vit. D binding protein binds Vit. ___ from the skin or intestine where it undergoes _____ in the ER ( by 25 hydoxylase). This reaction requires __, ______ and _____.
Vit. D3. Hydroxylation. Mg, NADPH & Oxygen.
In the mitochondria of the renal proximal convoluted tubule, 25 mono hydroxy D3 from the liver is converted to its active form by hydroxylation at position C1 by
1a-hydroxylase
Three enzymes that are needed for the activation of Vit. D in the kidney
- Flavoprotein, renal ferredoxin reductase
- Iron sulfur protein
- Cytochrome P450
32-AA peptide secreted by parafollicular C cells of the thyroid gland. Employed therapeutically to relieve the symptoms of osteoporosis. Formed by proteolytic cleavage of a larger prepropeptide which is the product of the CALC1 gene.
Calcitonin
A protein made by osteoclasts adn responsible for attaching osteoclasts to bone
Osteoporin
Shown to reduce the synthesis of osteoporin. Has counter effects of parathyroid hormone.
Calcitonin
PTH has primary control for these electrolytes
Calcium and Phosphate
Calcitonin reduces blood calcium levels in 3 ways: dec Ca _____ by the intestines, dec ________ in bones and dec _____ & _____ reabsorption by the kidney tubules.
Absorption. Osteoclast activity. Calcium & Phosphate.
Calcitonin prevents __________ resulting from absorption of Ca from foods during a meal.
Postprandial hypercalcemia
Calcitonin ______ mineralization of skeletal bone. And regulates ______.
Promotes. Vit. D
Calcitonin promotes against Ca loss from skeleton during periods of Ca stress such ah
Pregnancy and Lactation
Is a satiety hormone. It inhibits food intake in rats and monkeys. It may have CNS action involving the regulation of feeding and appetite.
Calcitonin
Receptor of Calcitonin with seven membrane spanning regions which is coupled by Gs to adenylyl cyclase and thereby to the generation of cAMP in target cells.
Serpentine G protein-coupled receptor
Secrete glucagon at outer rim of islet
Alpha cells
Secrete insulin at central islet
Beta cells
Secrete somatostatin and gastrin
Delata cells
Factors that increase glucagon secretion
Dec blood glucose, inc AA, Nor/Epi and Acetylcholine
Factors that decrease glucagon secretion
Inc blood glucose, insulin, somatostatin, fatty acids and ketoacids
Factors that increase insulin secretion
Inc blood glucose, AA, fatty acid, glucagon, ACh, GIP, growth hormone and cortisol
Factors that decrease insulin secretion
Dec blood glucose, somatostatin and Nor/Epi
Pathophysiology of DM
Hyperglycemia, hypotension, metabolic acidosis and hyperkalemia
Pathophysiology of DM: insulin deficiency
Hyperglycemia
Pathophysiology of DM: ECF volume contraction
Hypotension
Pathophysiology of DM: overproduction of ketoacids
Metabolic acidosis
Pathophysiology of DM: lack of insulin
Hyperkalemia
