SF4 Exam 2 General Flashcards
(406 cards)
1
Q
PTH Related Protein (PTHrP)
A
Sequence homology with PTH on N-terminal end. Paracrine/autocrine regulatory effect.
Function: Regulates Calcium flux through placenta (mom->child) during development. No calcium homeostasis effect in healthy adults
2
Q
Fate of Mature Osteoblasts
A
- 50-70% undergo apoptosis
- Lining Cells covering new bone
- Osteocytes
3
Q
Cortisol Effects on Lipid Metabolism
A
- Induces synthesis of hormone sensitive lipase
- Enhances Epinephrine/GH stimulation of Lipolysis
- Promotes fat deposition (excess Cortisol via appetite)
4
Q
How do Glucosteroids usually effect the processes in target tissues?
A
Mostly has a permissive role in regulating function rather than initiating it
5
Q
DIT + DIT
A
T4
6
Q
Malonyl CoA
A
Blocks entrance of Fatty Acids into Mitochondria
- Increased by Insulin
- Decreased by Glucagon
7
Q
Converts Dopamine to Norepinephrine within Secretory Granule
A
DBH
8
Q
Layers of Adrenal Gland by Primary Secretion
A
Adrenal Cortex:
- Zona Glomerulosa – Aldosterone
- Zona Fasciulata – Glucocorticoids
- Zona Reticularis – Androgens
Adrenal Medulla: Catecholamines
9
Q
Transports Iodide from Blood to Thyroid Gland
A
Na/I Symporter (NIS)
Utilizes gradient created by Na/K-ATPase
10
Q
Major Source of IGF-1
A
Liver
11
Q
Thyroid-Associated Opthalmopathy
A
Sign of Thyrotoxicosis assocciated typically with Graves Disease but also other Thyrotoxicosis
Characteristics:
- Periorbital Edema
- Proptosis (Graves Specific; not from TH)
- Lid Retraction (Other forms of Thyrotoxicosis too)
12
Q
Lineage of Osteoclsts
A
Precursor cells derived from Monocyte/Macrophage lineage recruited from circulation and activated.
Mononuclear cells fuse to form Multinucleated Preosteoclasts
These then differentiate into Osteoclasts
13
Q
Physiological Roles of Iodothyronine Deiodinases
A
- Maintain circulating pool of T3
- Local regulation of T3 production (target tissue)
- Thyroid Hormone Inactivation
14
Q
Cell converting Proglucagon into Glucagon
A
Pancreatic α Cells
15
Q
Chronic Effects of ACTH Release
A
- Increased Growth/Cell Prolif. in Zona Fasciculata and Reticularis
- Increased Synthesis of Steroidogenic enzymes, LDL receptors, Other proteins
16
Q
DNA Sequence THRs bind to
A
Thyroid Hormone Response Elements (TREs)
17
Q
Stress/Vasopressin Effect on Cortisol Release
A
Stress induces AVP’s release by CRH-secreting neurons. It potentiates CRH-mediated ACTH (has no effect itself however)
18
Q
Decrease IGFBP Affinity for IGF1
A
- Binding to target cells
2. Degradation by IGFBP Proteases
19
Q
GLUT2
A
Bidirectional transporter with low affinity for glucose. Takes in glucose when levels in portal system high.
When hepatic glucose high (blood glucose < 5mM), glucose exits cell via GLUT 2
20
Q
Provide Docking Sites in IGF-1 Receptor Pathway
A
- Phosphotyrosines on Receptor
2. Insulin Receptor Substrate-1 (IRS-1)
21
Q
Products of Proinsulin Cleavage
A
- Insulin
2. C Peptide
22
Q
Promotes Fatty Acid Synthesis in Liver
A
Insulin
23
Q
ACTH Receptor in Adrenal Cortex
A
Melanocortin-2 Receptor (MC2R)
24
Q
Inhibits OPG Production
A
PTH
25
Metabolic Processes Suppressed by GH
1. Glucose Uptake & Oxidation
| 2. Protein Breakdown (Fed State)
26
Nuclear Localization Signal
Domain on Steroid Hormone receptors allowing it reside in nucleus or translocate to the nucleus when activated
27
Incretin Defect in T2DM
Incretin secretion intact; β cell response is impaired
28
Inhibits RANK-L Expression
Estradiol
29
Insulin Receptor
Receptor Tyrosin Kinase
α subunit inhibits β subunit's tyrosine kinase activity in ABSENCE of insulin.
β subunit autophosphorylates its other residues and other intracellular tyrosines
30
Increases Glucokinase expression
Insulin
31
Mechanism of Reabsorption: Distal Convoluted Tubules
Transcellular (Saturable Active Transport)
Regulated by PTH (TRPV5)
32
Enzyme necessary to export glucose after gluconeogenesis
Glucose 6-phosphatase
33
Cause of Hyperinsulinemia
GH Excess
34
Glucose Transporter in β Cells
GLUT2
35
Matrix Digestion Products from Bone Resorption
Serve as markers in serum/urine
1. CTX (C-Terminal Telopeptides of Type 1 Collagen)
2. NTX (N-Terminal Telopeptides of Type 1 Collagen)
36
Mechanism for Genes Repressed by T3 Binding
1. Transcription is stimulated in the absence of T3/THR
| 2. T3/THR bind to negative TRE to repress transcription
37
Iodothyronines
1. Thyroxine (T4)
2. Triiodothyronine (T3)
3. Reverse T3 (rT3)
38
Calcium-Sensing Receptors (CaSR)
G-protein coupled receptor on Chief Cells. Monitor changes in Serum Ca.
Gi: Inhibit Adenylyl Cyclase
Gq: Activate Phospholipase C
39
Action: Phosphorylase Kinase and Inhibitor 1
Induce conversion of Phosphorylase b to Phosphorylase a, promoting Glycogenolysis
40
Precursor of Glucagon
Preproglucagon
41
Major Organ Involved in Calcium Homeostasis
1) Skeleton
2) Small Intestine
3) Kidneys
4) Parathyroid Glands
42
Enzyme Phosphorylating Glucose in β Cells
Glucokinase
43
Indicator of Daily Cortisol Output
24-hour urinary excretion of unmetabolized cortisol (even though 99% of urinary cortisol is metabolized)
44
Principal Targets of Insulin
1. Liver
2. Skeletal Muscle
3. Adipose Tissue
45
GH Excess in Adulthood
Acromegaly
46
Serine Phosphorylation and Insulin
1. Reduce signal intensity by serine phosphorylation on Insulin Receptor
2. Phosphorylation of IRS proteins has inhibitory effect on transduction
47
Thyroid Hormone effects on Growth Hormone
1. Synergistic/Permissive effect on action of Growth Hormone and others
2. Stimulates Growth Hormone synthesis/release at Pituitary Gland
48
Rate-Limiting Step in Steroid Biogenesis
Transfer of Cholesterol to Inner Mitochondrial Membrane. See StAR protein
49
Cortisol Effects on Carbohydrate Metabolism
1. Prevents Hypoglycemia
2. Promotes Hepatic Gluconeogenesis
3. Permissive Effect on Glycogen Formation
4. Decrease GLUT-4 Translocation
50
Functions of IGF Binding Proteins (IGFBP)
1. Provide circulating reserve of IGF
2. Increase half-life of IGF
3. Modulate bioavailability
4. Potentiate/Inhibit IGF action
51
Mechanism of H+ Secretion by Osteoclasts
Membrane-Associated H+-ATPase. Dissolves Hydroxyapatite crystals in bone matrix
52
Catecholamine Transport in Blood
1. Albumin (59%)
| 2. Free Catecholamines
53
Clinical markers of Hashimoto Thyroidits
1. Anti-TPO antibodies
| 2. Anti-TG Antibodies
54
Signaling Pathway Activated by IGF-1
Ras/Map Kinase Pathway
55
PI-3 Kinase / Akt Signal Transduction Pathway
Part of Insulin effects. Activated Pi-3 kinase phosphorylates Phosphoinositides on cytoplasmic face of membrane.
Resulting Pi 3-phosphates serve as docking sites for signaling proteins, including PKB/Akt
56
Causes of Hypoglycemia
1. Drugs potentiating effects of insulin or interfering with gluconeogenesis
2. Insulinomas
3. Rapid Gastric Emptying
4. Adrenal/Pituitary Insufficiency
5. Liver Disease
6. Inborn error of Carb. Metabolism
57
Effects of IGF-1 Binding
1. Stimulation of DNA, RNA and Protein Synthesis
2. Cell Proliferation
3. Insulin-like Effects on Adipose/Muscle Cells
58
(Adrenal) Medullary Plexus
Former from merging of Medullary Arterioles and Cortical Sinusoids
59
Lid Retraction
Occurs in Thyrotoxicosis due to over-activity of Sympathetic Nervous System. Not just in Graves Disease but other Thyrotoxicosis
60
Cushing Syndrome and Causes (ordered by importance)
Excessive Cortisol secretion
1. Ingestion of Pharmacological Glucocorticoids
2. Excessive Secretion of ACTH (Cushing **Disease**)
3. Ectopic Non-Endocrine ACTH-secreting Tumor
4. Adrenal Cortex Tumor
61
Secondary Aldosteronism
Caused by inappropriate activation of Renin-Angiotensin System
62
Glucose Transporter in Skeletal Muscle
GLUT4
63
Mechanism of Matrix Protein Digestion by Osteoclasts
Cathepsin K (Protease) secretion
64
Innervation of Adrenal Medulla
Cholinergic Preganglionic Fibers
65
24,25(OH)2D
Second most abundant circulating metabolite of Vitamin D.
Formed from 25(OH)D by 24-hydroxylase, expressed in the Kidney and 1,25(OH)2D target tissue
66
Insulin Effects on Carbohydrate Metabolism in Liver
1. Promotes Glycogen Storage
2. Promote Glycolysis
3. Inhibits Glycogenolysis
4. Prevents Release of Glucose
5. Inhibits Gluconeogenesis
6. Stimulates Fatty Acid Synthesis
67
Endemic Gioter
Low iodide intake common in third wold countries. Decreased Thyroid Hormone production leads to increased TSH output
68
Secondary Adrenocortical Insufficiency and Causes
Insufficient ACTH Production. Note: this wouldn't affect Aldosterone
1. Prolonged Administration of Pharmacological Glucocorticoids (negative inhibition of Axis, depression of ACTH leads to Adrenal Atrophy)
2. Pituitary Lesion (associated with Panhypopituitarism)
Usually associated with Renin and Renal Insufficiency
69
Stimulates Production of IGF-Binding Proteins in the Liver
Growth Hormone
70
Definition: Sensitivity
Ability of target cell to recognize and respond to hormone in proportion to intensity of signal
71
Affect Circulating TBG Levels
1. Malnutrition
2. Liver/Kidney Disease
3. Synthesis Stimulated by Estrogens
72
Mechanism of Reabsorption: Ascending Limb, Loop of Henle
Passive Paracellular and Transcellular
73
Phosphate Uptake in Small Intestine
Na+-Phosphate (Na+/Pi) Cotransporter (NaPi-IIb) on Apical Membrane.
Active transporter, using energy from Na/K-ATPase Na gradient.
Expression increased by:
1) Vitamin D3
2) Low Dietary Phosphate
74
Location of Magnocellular Cells
Supraoptic and Paraventricular Nuclei (Hypothalamus)
75
TRPV5
Epithelial Calcium Channel. Apical/luminal side in active Calcium Reabsorption in the Kidneys.
PTH induces its transcription and inhibits its removal from the plasma membrane.
76
Anions Competing for Sites on NIS
1. Perchlorate (HCLO4-)
2. Thiocyanate (CNS-)
3. Pertechnetate (TcO4-)
77
Lipoprotein Lipase
Synthesis induced by Insulin in fat and skeletal muscle cells.
LPL is translocated to Endothelial cells and breaks down TAGs associated with circulating Chylomicrons and VLDLs.
Converts them to Fatty Acids and Glycerol
78
Primary Hypothyroidism and Causes
Failure of the Thyroid Gland
1. Hashimoto's Thyroiditis (95% in US)
2. Inadequate Dietary Iodine
3. Surgical Removal, Radioactive Iodine Treatment, Antithyroid Drug Administration
79
P450c17
Enhances 17,20-lyase activity. Protein expressed in Zona Fasciulata and Zona Reticularis.
Zona Reticularis has cofactors enhancing P450c17/17,20-lyase activity which mean it synthesizes mainly androgens and only small amounts of glucocorticoids.
80
Adrenocorticotropic Hormone Precursor found in all three zones of the Adrenal Cortex
All three can synthesis pregnenolone and progesterone from cholsterol
81
Clinical indicator of Adrenal Androgen Release
DHEA and DHEAS in plasma
82
Thyroid Hormone Levels during Fast
1. T4 levels remain constant
| 2. T3 drops due to decrease in T4->T3 conversion
83
Bigger Effect: Thyroid Hormone Negative Feedback on Hypothalamus or Pituitary Gland?
Pituitary Gland
84
Definition: Threshold
Minimum concentration to produce detectable response
85
Release Pattern of Thyroid-Stimulating Hormone
Pulsatile with Circadian Pattern. Higher late in evening
86
Principal Regulator of PTH Secretion
Concentration of ionic calcium in Extracellular Fluid (Chief cells are very sensitive to 2-3% deviations)
87
Intracellular Mechanism of GHRH Binding
G protein activation of Adenylyl Cyclase. cAMP/PKA mechanism activates voltage-gated Ca2+ channels.
88
Mechanism for Genes Activated by T3 Binding
1. Unoccupied receptor binds to TRE and functions as a repressor of gene transcription.
2. Histone Deacetylase (HDAC) and Corepressor Proteins (CoR) recruited
3. Binding promotes dissociation and association of separate Coactivator Protein Complex
89
Physiological Stimuli of GH Release
1. Exercise
2. Stress
3. Sleep
4. Postprandial Hypoglycemia
5. Protein Rich Meal / IV infusion (Arginine esp)
6. Sex Steroids
7. Ghrelin
90
Apical membrane Calcium Channels in Small Intestine
1. TRPV6
2. TRPV5
Synthesis increased by Vitamin D3
91
Anti-Inflammatory Effects of Cortisol
1. Blocks expression of pro-inflammatory Cytokine Genes (TNFα, Interleukin-1)
2. Inhibits Phospholipase A2
3. Inhibits NO Synthase expression
4. Inhibits release of Histamine and Serotonin from Mast Cells
5. Inhibits release of Proteolytic Enzymes from damage tissues/phagocytes
92
Primary Cause of Growth Hormone Excess
Pituitary Adenoma
93
Rate-Limited Step in Catecholamine Synthesis
Conversion of Tyrosine to DOPA by Tyrosine Hydroxylase
94
Cell Type Secreting PTH
Chief Cells
95
Trigger of Calcitonin Secretion
1. Plasma Ca rising above 9 mg/dL
| 2. Gastrin (supraphysiological levels)
96
Somatomammotropin Family of Hormones
Single chain proteins containing intrachain disulfide bridges
Pituitary Hormones:
1. Growth Hormone (GH)
2. Prolactin (PRL)
Placental Hormones:
1. Placental GH (hGH-V)
2. Chorionic Somatomammotropin (hCS) / Placental Lactogen (hPL)
97
Dissociation Constant
Concentration when 1/2 of receptors occupied; Kd = [H] and also 1/Ka
98
Primary Source of Norepinephrine in Circulation
Nerve terminals
99
Release Structures for Anterior Pituitary Gland Secretion
1. Primary Capillary Plexus of Median Eminence (Hypothalamus)
2. Carried to Anterior Pituitary via Hypothalamohypophyseal Portal Vessels
3. Terminate in Secondary Capillary Plexus in Anterior Pituitary
100
Principal Adrenal Androgen Released by Zona Reticularis
Dehydroepiandrosterone (DHEA). Primarily released as DHEA Sulfate (DHEAS)
Also small amounts of Androstenedione
101
Multiple blood samples of this hormone are taken at timed intervals and combined to test levels
Integrated GH Concentration
102
Mechanisms of Calcium Uptake in Small Intestines
Transcellular (affected by Vitamin D) and Paracellular
103
Paracrine Regulator in Pancreas Inhibiting Insulin and Glucagon Release
Somatostatin
104
Metabolic Processes Stimulated by GH
1. Lipolysis (esp. Visceral fat)
2. Gluconeogenesis
3. Glycogenolysis
4. Protein Production (Fed State)
5. Pancreatic Cell Growth / Function
105
Cell converting Proglucagon to GLP-1, GLP-2
Intestinal L Cells
106
Fasting Actions of Glucagon
1. Stimulates Glycogenolysis
2. Inhibits Glycogen Synthase
3. Inhibits Glycolysis
4. Promote Glucogenesis
107
Location of Thyroid Gland
Two lobes either side of the trachea, below the Larynx
108
Summary of PTH Effects:
1. Stimulates Calcium Reabsorption
2. Stimulates Phosphate Excretion
3. Stimulates Vitamin D Synthesis
* Serum/Urine Calcium: Increases
* Serum Phosphate: Decreases
* Urine Phosphate: Increases
109
Adrenal Hormone whose main stimulator is not ACTH
Aldosterone (Angiotensin II and K to lesser degree)
110
Prolongs lifespan of Osteoclasts
RANK/RANK-L system inhibits apoptosis in Osteoclasts
111
Steroid Hormone Transport in Blood
1. Coritcosteroid-Binding Globulin (CBG)
2. Sex Steroid-Binding Globulin (SHBG)
3. Vitamin D-Binding Globulin
4. Albumin (non-specific, low affinity)
5. Free fraction
112
Intracellular Mechanism: β1,2,3-adrenergic receptors
increased cAMP
113
Hepatic Glycogenolysis
Mobilizes glycogen into glucose. Action mediated by cAMP
PKA Phosphorylates:
1. Phosphorylase Kinase (activate)
2. Inhibitor 1 (activate)
3. Pathway inhibiting Glycogen Synthase Activity
114
Alkaline Phosphatase
Diffuse into blood and used as indicator of bone formation.
Levels elevated during childhood growth, following major fracture, and in certain bone destroying disease.
115
Transports Epinephrine back into Secretory Granule after conversion from NE
VMAT (again)
116
Mechanism to Regulate Quantity of PTH Released
Degradation of stored PTH in Secretory Vesicles. Increase in release of inactive C-terminal fragments when PTH not needed
117
Neuroglycopenia
Deficient supply of glucose to CNS
118
Precursor of Insulin
Proinsulin
119
P450scc
Side-chain cleave enzyme which converts Cholesterol to Pregnenolone.
Located in Inner Mitochondrial Membrane
120
Factors Controlling Osteoblast Growth/Differentiation
1. Bone Morphogenic Proteins
2. Growth Factors (ex: IGF-1)
3. Cytokines (ex: Interleukins 1 and 6)
4. Mechanical Forces
121
Propylthiouracil
Blocks iodination of Thyroglobulin and inhibits conversion of T4 to T3.
Antithyroid drug which could the cause of Primary Hypothyroidism
122
Humoral Hypercalcemia of Malignancy (HHM)
Tumors release humoral agents into circulation promoting resorption. Associated with a variety of malignant tumors.
PTHrP is the most common mediator
123
Causes of Symptoms of Hypoglycemia
1. Sympathetic Activation
| 2. Neurogylcopenia
124
Neurons releasing Hypophysiotropic Hormones
Parvicellular Neurons (Hypothalamus)
125
Corticotrope (Hypothalamic and Anterior Pituitary Hormones)
Hypothalamic Hormones:
1. Corticotropin-Releasing Hormone (CRH) [++, Gs]
2. Arginine Vasopressin (AVP) [++, Gq]
Anterior Pituitary Hormones:
1. Adrenocorticotropic Hormone (ACTH)
2. Beta-Lipotropin (β-LPH)
126
Diabetic Ketoacidosis
First indicator in children/adolescents with T1DM (not always.
1. Uncontrolled hyperglycemia
2. Metabolic acidosis
3. ketosis
127
Serious Acute Complications in T1DM
1. Diabetic Ketoacidosis
| 2. Hyperosmolar Hyperglycemic State (HHS)
128
PTH Effect on Vitamin D Metabolism
Induces 1α-renal hydroxylase activity in the Proximal Tubules (conversion of 25(OH)D3 to 1,25(OH)2D3)
129
Organification of Thyroglobulin
Binding of Oxidized Iodide to Thyroglobulin
130
Hormone Abnormality leads to Hypercholsterolemia
Hypothyroidism
131
Phospholipase A2
Catalyzes synthesis of inflammatory agents such as Prostaglandins, Thromboxanes, and Leukotrienes from Arachidonic Acid
Synthesis inhibited by Cortisol
132
Stimulates RANK-L Expression
PTH
133
Test Most Commonly Used when Endocrine Gland Hyperfunctional
Suppression Test
134
Cells Secreting Catecholamines into Blood Stream
Chromaffin Cells
135
Enzyme Hydroxylating 25(OH)D to 1,25(OH)2D
Renal 1α-hydroxylase
136
Action of Thyroid Hormone in Prolonged Fast
15-20% decrease in basal metabolic rate
137
Wolff-Chaikoff Effect
Thyroid Gland Autoregulation.
Ingestion of excessive amounts of iodine suppresses thyroid hormone synthesis. Suppresses expression of NIS and Thyroid Peroxidase.
138
Type of Neurons Posterior Pituitary Gland Axons Originate from
Unmyelinated axons from Magnocellular Neurons
139
Definition: Maximum Response
Effect produced by a saturating concentration of hormone
140
Neurophysin Domain
Found on the prohormone of ADH/Oxytocin.
Cleaved off and acts as a Intraneuronal Carrier, binding the hormone. Released alongside the hormones by with no physiological function.
141
Bone Resorption Initiation
Binding of hormones, cytokines, or other factors to receptors on Osteoblasts.
1. Osteoblasts degrade unmineralized osteoid
2. Increase expression of RANK-L
3. Synthesize and release M-CSF
142
Cell Secreting Calcitonin
Parafollicular Cells (C Cells of Thyroid)
143
Effects of Chronically-Elevated Insulin Levels (on Insulin Receptors)
1. Increased rate of receptor-mediated endocytosis
| 2. Decreases rate of Insulin Receptor synthesis
144
Blood Transport of Glucocorticoids
1. Corticosteroid Binding Globulin (CBG) (75%)
2. Albumin (15%)
3. Free Cortisol
145
Steroid Hormone Receptors when Unoccupied
Form complexes with Chaperone Proteins (Heat-Shock Proteins). When steroid binds it dissociates.
146
Conversion Products of DHEA and Androstenedione Peripherally
1. Testosterone
| 2. Dihydrotestosterone
147
Gonadotrope (Hypothalamic and Anterior Pituitary Hormones)
Hypothalamic Hormone:
1. Gonadotropin-Releasing Hormone (GnRH) [++, Gq]
Anterior Pituitary Hormone:
1. Follicle Stimulating Hormone (FSH)
2. Lutenizing Hormone (LH)
148
Majority Source of Circulating T3 and rT3
Peripheral Metabolism of T4
Especially: Liver and Kidney
149
Stimulates OPG Production
Estradiol
150
Thyroid Hormone Effects on Metabolism
Potentiates Catecholamine Effects on:
1. Lipolysis
2. Glycogenolysis
3. Gluconeogenesis
Likely by β-adrenergic receptor upregulation
151
Catalytic Activity of GH Receptor
No intrinsic activity; relies on Janus Kinases (JAK2)
152
Main IGF Binding Protein
IGFBP-3
153
How are the two forms of Growth Hormone produced
Differential splicing of mRNA
154
Thyroid Hormone Negative Feedback
Hypothalamus:
1. T3 inhibits prepro-TSH gene expression
Pituitary (Major):
1. Negative Response Element for Thyroid Hormone Receptor for TSH Subunit genes
2. Intracellular T3 downregulates TSH Receptor
155
Mediators of Glucagon Release during Hypoglycemia
1. Sympathetic Stimulation
| 2. Rise in Circulating Catecholamines (β2 receptor)
156
Sympathetic Nervous System Effect on Insulin Release
Exercise and stress inhibit insulin release.
Mediated by α2-adrenergic receptors coupled to Gi protein
157
Promotes Transcription of Tyrosine Hydroxylase
Acetlycholine
158
Adrenal Hormones with Negative Feedback Inhibition of ACTH Release
Only Cortisol.
Androgens and Aldosterone do not.
159
Compact Bone
80% of total bone mass. Densely packed matrix making it firm and strong. Forms the shafts of long bones. Covers ends of long bones and surfaces of other bones.
160
Primary Target of Glucagon
Liver
1. Glycogenolysis
2. Gluconeogenesis
161
Non-Autoimmune Causes of Thyrotoxicosis
Ordered by Occurrence
1. Toxic Multinodular Goiter (incidence higher in iodine deficient areas; hyperfunctioning nodules)
2. Toxic Adenoma (single hyperfunctioning nodule; Gain-in-Function TSH Receptor Mutation)
3. Secondary Hyperthyroidism from TSH-Secreting Pituitary Adenoma
162
Paracrine Suppressors of Glucagon
Insulin and Somatostatin
163
Increases the half-life of Glycoprotein Hormones
Glycosylation of the protein after the subunits are combined.
164
Principal Substrates for Hepatic Gluconeogenesis
1. Amino Acids from Skeletal Muscle
2. Lactate from Skeletal Muscle and RBCs
3. Glycerol from Fat
165
Counterregulatory Effects of Growth Hormone and Cortisol
Released in Anterior Pituitary after Hypothalamic Releasing Hormones released in response to Hypoglycemia.
Slow acting, not important in acute but instead prolonged Hypoglycemia
166
Transcription Factors Activated by PKA upon GHRH
1. GH
| 2. GHRH Receptor
167
Enhances GH release stimulated by GHRH
Ghrelin
168
Mechanism for Ca Crossing Basolateral Membrane in Small Intestines
Calcium ATPase (PMCA)
169
Synthetic Glucocorticoids
Enhanced activity due to increased affinity for receptor and delayed clearance.
1. Dexamethasone
2. Prednisone
170
Number of Parathyroid Glands
Four
171
Vitamin D Effects on Parathyroid Gland
Negative feedback on PTH secretion
1. Inhibits PTH gene
2. Induces expression of CaSR
3. Induces expression of Vitamin D Receptor (VDR)
172
RANK
Receptor expressed on OsteoClast precursors. Binds RANK-L
Turns on signaling pathways in the OsteoClast precursors, promoting differentiation and fusion into multinucleated cells.
173
Association Constant Formula
Ka = [HR] / [H][R]
174
Cells in Epiphyseal Growth Plate Expressing Both GH and IGF-1 Receptors
Chondrocytes
175
Hypophysiotropic Hormones with Gq Mechanism
1. TRH
2. GnRH
3. AVP
176
Effects of Chronic TSH Stimulation
1. Growth of Thyroid Gland
| 2. Capillary Proliferation
177
Catalyzes MIT and DIT Coupling
Thyroid Peroxidase
178
Mechanism of Vitamin D Receptor (VDR)
Functions as a ligand-activated transcription factor
179
Incretins
Hormones released in intestinal mucosa by endocrine cells in response to presence of nutrients in lumen
1. Glucose-Dependent Insulinotropic Peptide (GIP)
2. Glucagon-like Peptide-1 (GLP-1)
180
Decreased Thyroid Hormone Binding Affinity to TBG
Salicylates
181
Induces Aldosteron Synthesis by Activating Voltage-Gated Ca2+ Channels
K+
182
Steroid Hormone Receptor Antagonist
Binds to receptor, inducing conformation change that prevents coactivators from binding and/or favors corepressor binding to receptor
183
Growth Hormone Carrier in Blood
GH Binding Protein (same structure as external portion of receptor)
184
Thyrotoxicosis
Clinical syndrome characterized by Thyroid hormone excess. Symptoms result from:
1. Increased metabolic activity
2. Increased catecholamine sensitivity
185
Sulfonylureas
Oral hypoglycemic drug used to treat T2DM.
Binds to SUR subunit of ATP-Gated K+ Channels in β cells, closing channel
186
Glucose Transporter in Adipose Tissue
GLUT4
187
Limits Substrate Availability for Gluconeogenesis
Insulin
188
Intracellular Mechanism: α1-adrenergic receptor
Increased IP3, Ca, DG
189
Osteocytes
Quiescent cells communicating with Lining and other cells by means of Canaliculi an gap junctions. Network supports bone metabolism and detects changes in mechanical strain.
Quiescence lasts until next remodeling cycle
190
Enzymes involved in Intraglandular Degradation of PTH
Secretory Vesicle Proteases. Degrade intact PTH into inactive C-terminal fragments
191
Blood Transport of Mineralocortiocoids
1. No specific aldosterone-binding globulin
2. Weakly binds Corticosteroid-Binding Globulin (CBG)
3. Albumin (most aldosterone)
4. Free Aldosterone (40-50%)
192
Release of Free Cholesterol in Steroidogenic Cells
LDLs enter the cell via endocytosis. They undergo hydrolysis in the lysosomal compartment to release the free cholesterol
193
Axis-Driven Feedback Loops
Tropic hormones can inhibit their own release, so can the final product
194
Action of Fetal Adrenal Gland
Produces large amounts of DHEA Sulfate (inner fetal zone; neocortex largely predifferentiated)
DHEAS converted to Estrogens by the Placenta
195
ACTH Regulation of Adrenal Androgen secretion
ACTH stimulates Adrenal Gland but does not increase during Adrenarche
196
Thyroid Hormone Effect on Cardiac Output
Increases both contractility and heart rate.
Promotes Transcription of:
1. β Adrenergic Receptors (T3 increases sensitivity to stimulation)
2. Gs proteins
3. Other Cardiac Muscle Related Proteins
197
Pharmacological Iodide doses treat..
Acute Thyrotoxicosis
198
Primary Source of Epinephrine in Circulation
Adrenal Medulla (only source)
199
Layers of Adrenal Cortex (Superficial to Deep)
1. Zona Glomerulosa
2. Zona Fasciulata
3. Zona Reticularis
200
Thyrotrope (Hypothalamic and Anterior Pituitary Hormones)
Hypothalamic Hormone:
1. Thyrotropin-Releasing Hormone (TRH) [++, Gq]
Anterior Pituitary Hormone:
1. Thyroid Stimulating Hormone (TSH)
201
Clinically Measured to Assess Vitamin D Status
25-hydroxyvitamin D [25(OH)D]
202
Causes of Congenital Hypothyroidism
1. Infants born with little/no thyroid tissue (80-85%)
2. Inherited defect in synthesis/metabolism
3. TSH-R blocking antibodies transferred from mother via placenta with autoimmune thyroid deficiency (transitory)
4. Endemic iodide deficiency
203
Cholesterol Esterase
Free cholesterol in the Steroidogenic Cell can either enter the Steroidogenic pathway or be Esterified into a Cholesterol Ester (storage). These coalesce into lipid droplets.
Cholesterol Esterase mobilizes the storage of Cholesterol Esters back into free cholesterol.
204
Congenital Adrenal Hyperplasia (CAH) and Causes
Genetic enzymatic deficiencies in biosynthesis of Adrenal steroids. Hyperplasia due to deficiency in Cortisol synthesis, decreasing negative feedback and leading to a rise in ACTH secretion/tropic effects on Adrenal Gland.
Most frequent defect: 21-hydroxylase (salt wasting)
Could also be 11β-hydroxylase (retain DOC)
205
Shift Right or Left -- Decrease in Sensitivity (Concentration-Response Curve)
Shift to Right
206
NADPH Oxidase
Generates H202 (hydrogen peroxide) in Follciular Lumen, which then acts as an electron acceptor in the Oxidation of Iodide
207
Mineralocorticoids
1. Aldosterone
2. DOC
3. Cortisol (has activity but its a Glucocorticoid)
208
Release Structure for Posterior Pituitary Gland Secretion
Infundibulum
209
Stimulation test for Prolactin
TRH
210
Hormone for which you would do Arginine Infusion stimulation test
Growth Hormone
211
Endocrine Cell Clusters in Pancreas
Islets of Langerhans
212
Intracellular Calcium Binding Protein (Small Intestine)
Calbindin-D9k
Protects cell against cytotoxic effects of elevated calcium. Maintains the gradient for influx.
Synthesis increased by Vitamin D3.
213
Ruffled Border
Elaborate membrane structures formed on Osteoclast-sealed areas of contact with bone
Secrete hydrogen ions onto bone surface
214
Principal Precursor for Steroidogenesis
Low-Density Lipoprotein (LDL)
Remainder from other lipoproteins or de novo synthesis from Acetate
215
PKB/Akt
Part of Insulin effects and Pi-3 Kinase / Akt Pathway.
Initiates signaling cascade promoting translocation of GLUT4 to membrane.
216
Intracellular Mechanism of Somatostatin Binding (Pituitary Gland)
1. Inhibition of Adenylyl Cycle
| 2. Activation of K+ channels (hyperpolarizing)
217
11β-Hydroxysteroid Dehydrogenase 2 (11β-HSD2)
Converts Cortisol to Cortisone. Expressed in target tissues, such as the kidney. Reason that cortisol is a weak mineralocorticoid (converted rapidly).
Deficiency/inhibition can cause Mineralocorticoid Hypertension
218
Contained in Follicle Lumen
Colloid
219
Principal Carrier of Vitamin D in Blood
Vitamin D Binding Globulin (DBG)
220
Thyroid Hormones in Postnatal Growth
Required for normal growth but will not promote growth without GH. Promotes linear growth by increasing GH secretion.
221
Laron Dwarfism
High GH levels but IGF not produced in Response
Type 1: Deletions/mutations in GH Receptor gene
Type 2: Post-GH Receptor Defect
222
Cholecalciferol / Vitamin D3
Formed from the reaction of 7-dehydrocholesterol with UV light in the skin
223
MIT + DIT
T3 or rT3
224
Ergocalciferol / Vitamin D2
Vitamin consumed in diet from plant sterol reaction with ultraviolet.
225
Products of Oxidized Iodide Binding to Thyroglobulin
1. Monoiodotyrosine (MIT)
| 2. Diiodotyrosine (DIT)
226
Cell Secreting Calcitonin
Parafollicular (C Cells) of Thyroid
227
Proptosis
Anterior bulging of eyeballs, seen in Graves Disease. Due to increase in Retroorbital tissue.
Mediated by Autoimmune mechanisms so ONLY in Graves Disease, not other Hyperthyroid conditions
228
Stimulates Alveolar Maturation and Surfactant Production in Development
Cortisol
229
Insulin Effect on Ketogenesis
* Direct: Stimulates formation of Malonyl CoA, which blocks transport of fatty acids into the Mitochondria
* Indirect: Decreases FAs in circulation by inhibiting Lipolysis
230
Myxedema Coma
Life threatening complication in patients with poorly controlled long-term hypothyroidism. Coma rare
Triggered by: Severe illness, stress, surgery or traumatic injury
Symptoms:
1. Deterioration of mental status
2. Extreme hypothermia
3. Areflexia
4. Bradycardia
5. Respiratory depression
231
Receptor Type: IGF-1 Receptor
Receptor Tyrosine Kinase
232
Depolarizes β Cell during Insulin Secretion
ATP-Gated K+ Channel
ATP binds to channel and inhibits K+ efflux
233
Osteoprotegerin (OPG)
Soluble protein inhibiting RANK-L induced differentiation of PreOsteoClasts. Acts like a decoy receptor than binds RANK-L, preventing it from activating RANK on OsteoClasts and PreOsteoClasts.
Released by Osteoblasts and Osteoblast Lineage Cells
234
Hormones Released from Posterior Pituitary Gland
1. ADH (Vasopressin)
| 2. Oxytocin
235
Hormones Indirectly Stimulating Insulin Release Because Action Antagonizes Insulin
1. GH
| 2. Cortisol
236
Site of Cleavage of Prepro-PTH
Trans-Golgi Network
237
Exhibits symptoms of Hypothyroidism. Patients have elevated MIT and DIT in serum and Urine.
Microsomal Iodotyrosine Deiodinase Deficiency
238
Osteomalacia
Vitamin D deficiency impairing bone mineralization AFTER EPIPHYSEAL PLATE CLOSES
239
Majority Source of Circulating T4
All from Thyroid
240
25-hydroxyvitamin D [25(OH)D]
Formed in the liver, converted from Cholecalciferol. Formation is unregulated. Has little biological activity and long circulatory half-life. Most abundant form in blood.
241
Cortisol Effect on Cardiovascular System
Require for response to Vasoconstrictors (Catecholamines and Angiotensin II)
242
Addison Disease and causes
Primary Adrenocortical Insufficiency. Defect within the adrenal gland
1. Destruction of gland by Tuberculosis, Tumor, etc.
2. Autoimmune
3. Inborn error of steroid hormone synthesis
243
Androgen effect on Skeletal Growth
Increases thickness of cortical bone by stimulating Periosteal Bone Expansion
244
PTH Actions on Bone
Promotes differentiation and activation of osteoclasts indirectly to stimulate resorption of bone by Osteoclasts.
Binds and activates PTH/PTHrP receptors on OsteoBlasts (Stimulates RANK-L expression)
245
Function of Calcitonin
Major: Suppress bone resorption by Osteoclasts
Secondary: Increase calcium clearance
246
PTH Effects on Phosphate Balance
Increases urinary excretion by inhibiting reabsorption in Proximal and Distal Convoluted Tubules. Protects against Calcium Phosphate formation in Soft Tissues.
Effect on Proximal Tubules most important.
Promotes removal of Sodium-Dependent Phosphate Co-Transporters from Luminal Membrane.
247
Major Cause of Hypoparathyroidism
Autoimmune disorder and inadvertent removal of glands during surgery
248
Rickets
Vitamin D deficiency impairing bone mineralization IN GROWING BONES
249
7-dehydrocholsterol
Vitamin D precursor found in skin
250
Principal Extrinsic Regulator of Postnatal Growth
Nutrition
251
Deoiodinate MIT and DIT remaining in cell after Thyroid Hormone Secretion
Microsomal Iodotyrosine Deiodinase
252
Catecholamine-Degrading Enzymes
1. Monoamine Oxidase (MAO)
| 2. Catecholamine-o-Methyltransferase (COMT)
253
Binding Site of Oxidized Iodide on Thyroglobulin
Tyrosyl residue
254
Site of Conversion of DOC to Corticosterone in Zona Fasciculata
Mitochondria via 11β-hydroxylase
255
Hypophysiotropic Hormones with Gs Mechanism
1. CRH
| 2. CHRH
256
Trousseau's Sign
Hypoparathyroidism. Tetany in hand happens first, when serum calcium falls to 6 mg/dL
257
Glycoprotein Hormone α Subunits
All identical (single gene)
258
Absorptive State
Period of time during and after ingestion of meal when cell metabolism fueled primarily by nutrients absorbed from meal. Lasts about four hours
259
Examples of Genes Repressed by T3/THR binding to TRE
1. Thyrotropin-Releasing Hormone Receptor
| 2. TSH Subunits
260
Fundamental Difference Between Thyroid and Steroid Hormone Receptors
Thyroid Hormone Receptors can bind DNA when receptor occupied or unoccupied.
Steroid Hormone Receptor have to be occupied to bind DNA.
261
Paracrine Regulator in Pancreas Stimaulating Insulin Release
Glucagon
262
11β-Hydroxysteroid Dehydrogenase 1 (11β-HSD1)
Converts Cortisone to Cortisol (reversible).
Expressed in tissues with Glucocorticoid Receptors (liver, skin, adipose tissue, CNS)
263
Symptoms: Hypoparathyroidism
Clinical features due to hypocalcemia.
1. Neuronal membranes more permeable and excitable
2. Tetany from spontaneous discharge of peripheral nerves
264
Proopiomelanocortin Family of Hormones
Single gene precursor: Proopiomelanocortin (POMC)
Most Important Cleavage Product: ACTH
265
ACTH/Cortisol Release Patterns
Secretory pulses throughout day (7-13/day).
Cortisol release in Diurnal Rhythm, highest in morning when sleep-wake/light-dark cycles synchronized
266
Parathyroid Hormone Receptor 1 (PTH/PTHrP Receptor)
Binds PTH and also PTH Related Protein (PTHrP).
Mechanism: Increases intracellular cAMP level via Gs protein mechanism. Actions can be mimicked by cAMP analogs.
267
Release Pattern of Insulin
Episodic
268
Degradation and Excretion of Steroid Hormones
Degraded by conversion to inactive metabolites in the Liver.
Then conjugated to Glucoronic Acid or Sulfate to increase clearance by increasing solubility and decreasing binding affinity for proteins.
269
Macrophage Colony Stimulating Factor (M-CSF)
Promotes early differentiation of Monocyte/Macrophage lineage cells. Works with RANK-L to promote OsteoClastogenesis
Secreted by Osteoblast Lineage Cells
270
Normal Plasma Range for Calcium
8.5 - 10.3 mg/dL
271
Direct Effect of Hyperparathyroidism
Bone lesions (PTH-induced bone resorption)
272
Promotes Substrate Availability for Gluconeogenesis
Cortisol
273
Metabolites of Catecholamine Inactivation
1. Metanephrines
| 2. Vanillylmandelic Acid
274
Acute vs Hours/Days vs Prolonged Hypocalcemia Responses
Acute:
1. PTH degradation reduced
Hours/Days:
1. PTH gene transcription increased
2. Increased stability of PTH mRNA
Prolonged:
1. Increased rate of Chief Cell Production
275
Proteins of Bone Matrix formed by Osteoblasts
1. Type 1 Collagen
2. Alkaline Phosphatase
3. Osteopontin
4. Osteocalcin
5. Bone Sialoprotein
276
First Step in Steroid Hormone Biogenesis
Conversion of Cholesterol to Pregnenolone by P450scc
277
Endocrine Glands Secreting Steroid Horomones
1. Adrenal Cortex
2. Testes
3. Ovaries
4. Placenta
278
Functions of Insulin
1. Stimulate uptake of nutrients
2. Modulate metabolic enzymes
3. Promote nutrient storage
4. Regulate protein transcription
5. Induce cell growth and differentiation
6. Inhibit ketogenesis
279
Brain's Response to Hypoglycemia
1. Hypothalamus activates Sympathetics
2. Sympathetics act on Pancreatic Islets to stimulate glucagon and inhibit insulin release
3. Rapid rise in circulating Epinephrine
280
Arachidonic Acid Metabolite Promoting Intraglandular Degradation of PTH
Leukotrienes. Activated in Arachidonic Acid Pathway by CaSR Gq protein
281
90% of filtered calcium reabsorbed in the...
Proximal Convoluted Tubule and Thick Ascending Limb of Loop of Henle
282
TREs can form monomers, homodimers, or heterodimers with other Nuclear Receptor family members when binding DNA. Which combination has the highest binding affinity?
Heterodimer of:
1. T3 / THR
2. Retinoid X Receptor (RXR)
283
Mechanism for Insulin repression of Gluconeogenesis
1. Suppresses expression of Gluconeogenic enzymes
| 2. Inhibits protein catabolism (substrate)
284
Triggers Release of Insulin via Exocytosis
Voltage-Gated Ca2+ channels
285
Test Most Commonly Used when Endocrine Gland Hypofunctional
Stimulation Test
286
Receptor Tyrosine Phosphatases
Dephosphorylate Insulin-Receptor complexes after endocytosis
287
Anti-Inflammatory Proteins Induced by Cortisol
1. Interleukin-10
| 2. Lipocortin (Annexin) (inhibits Phospholipase A2)
288
Adrenarche
Circulating levels of adrenal androgens begin to rise in girls at 6-7, boys 7-8. Rises progressively through adolescence
NOT INITIATOR OF PUBERTY
289
Upregulate Renal 1α-hydroxylase
1. High PTH
2. Hypocalcemia (CaSR Pathway)
3. Hypophosphatemia
290
Major Site of Ketogenesis
Liver
291
Digest Thyroglobulin after Endocytic Vesicles fuse with Lysosomes
Lysosomal Proteases
292
Fate of Insulin Hormone-Receptor Complex
Major mechanism for Hepatic Clearance of Insulin
1. Receptors bound to insulin aggregated in Coated Pits
2. Complex taken in by endocytosis; receptor dephosphorylated
3. Acidic Endosome promotes dissociation of insulin from receptor
4. Insulin degraded. Receptor degraded or recycled.
293
RANK-L
Cell surface ligand on OsteoBlast lineage cells. Since it's on the surface there must be cell-to-cell contact
A soluble form is also produced by Osteoblasts
294
Mechanism for Insulin preventing release of glucose from Liver
Represses expression of Glucose 6-Phosphatase
295
How do you know a target tissue has Spare Receptors/
Maximum response reached when only a small fraction of receptors are occupied. This greatly enhances sensitivity of the cell to the hormone
ED50 < Kd
296
Downregulate Renal 1α-hydroxylase
1. 1,25(OH)2D (negative feedback)
2. Rise in [Ca]
3. Decrease in PTH
297
11β-hydroxylase
Catalyzes:
1. DOC -> Corticosterone
2. DOC -> Cortisol
298
GH Excess in Childhood
Gigantism
299
Stimulate Catecholamine Synthesis/Release
1. Sympathetic Activation
| 2. Glucocorticoids
300
Major Regulator of Ketogenesis
Increases with influx of Fatty Acids into Liver. Insulin has an indirect effect here in decreasing circulation of Fatty Acids
301
Type of Receptor: Growth Hormone Receptor
Cytokine/GH/PRL/Erythropoietin Receptor Family
302
Site for Conversion of 25(OH)D to 1,25(OH)2D
Proximal Tubules (Kidney)
303
Terminus Determining PTH Biological Activity
N-Terminal
Intact PTH 84 AAs, Synthetic N Termin Fragment 1-34 can induce same effects
304
Test designed to assess functional status of negative feedback system
Suppression test
305
Physiological Trigger(s) of Glucagon Release
1. Hypoglycemia
| 2. High-protein meal low in carbs (esp Arginine)
306
Sex Steroids in Postnatal Growth
Most important is Estradiol.
1. Responsible for puberty growth spurt
2. Promotes linear growth
3. Promotes maturation/fusion of Epiphyseal Growth Plate
3. Increase growth hormone secretion
307
Hormones for which Osteoblasts have Receptors
1. PTH
2. 1,25(OH)2D3
3. Estrogens
4. Glucocorticoids
308
Protein Sparing Effect
Amino acid release is reduced from 3 day to 40 day fast. Use of glucose limited to fewer organs with rising ketone body and FA use.
309
Target Cells of IGF-1
1. Fibroblasts
2. Chondrocytes
3. Osteoblasts
4. Adipocytes
5. Muscles
310
Incretin Receptors in β cells
G-protein coupled receptors stimulating glucose-dependent insulin secretion. Mechanism involves cAMP signaling
311
Catalyzes Oxidation of Iodide in Follicular Lumen
Thyroid Peroxidase (TPO)
312
Greater Affinity for IGF-1: IGFBP or IGF-1 Receptor
IGFBP
313
9% of filtered calcium reabsorbed in...
Distal Convoluted Tubules
314
Classical Symptoms of Diabetes
1) Polyuria - excessive urination
2) Polydipsia - excessive thirst
3) Polyphagia - excessive eating
315
Precursor to PTH
Prepro-PTH
316
Overview of Thyroid Hormone Effects on Cardiovascular Function
1. Controls Basal Metabolic Rate
2. Increases Cardiac Output
3. Potentiates Catecholamines
317
Pseudohypoaldosteronism
Tissue resistance / loss of function mutation in Mineralocorticoid Receptor
Characterized by:
1. Severe Salt Wasting (Neonates)
2. Hyperkalemia
3. Metabolic Acidosis
4. Failure to respond to Mineralocorticoid treatment
318
Thyroxine-Binding Globulin (TBG)
Highest affinity. Least abundant of Thyroid hormone binding proteins but binds most.
Affinity for T4 > T3
319
Osteocalcin
Another bone formation marker
320
Intracellular Mechanism: α2-adrenergic receptor
Decreased cAMP
321
Psuedohypoparathyroidism
Genetic disorder of target tissue resistance to PTH
322
Cortisol Effect on Bones/Calcium Homeostasis
Excess levels antagonize Vitamin D3 and increase risk for Osteoporosis
1. Calcium uptake by small intestine inhibited
2. Inhibit renal Ca reabsorption
3. Acts directly on bone to inhibit formation (lesser extent, promote resorption)
323
Transports Dopamine into Secretory Granule after conversion from DOPA
Vesicular Monoamine Transporter (VMAT)
[Catecholamine-H+ Exchanger]
324
Counterregulatory Hormones
Released in response to hypoglycemia (esp. Acute)
1. Glucagon
2. Epinephrine
3. Growth Hormone
4. Cortisol
325
Glucose Transporter in Liver
GLUT2
326
Endocrine Secretions in Pancreas
1. Insulin (β cells)
2. Glucagon (α cells)
3. Somatostatin (δ cells)
4. Pancreatic Polypeptide
327
Graves Disease
Most common cause of Thyrotoxicosis. Autoimmune disorder characterized by Hyperplastic Goiter.
TSH levels suppressed by high circulating levels of Thyroid Hormone
328
Hormone-Sensitive Lipase
Breaks TAGs down into Fatty Acids and Glycerol in Adipose Tissue.
* Stimulated by: Epinephrine
* Inhibited by: Insulin
329
Cancellous / Trabecular Bone
Arranged in meshwork of thin plates and spicules, giving it a sponge-like appearance. Orientation based on direction of forces. 20% of bone mass but 80% of surface area.
Inner portions of flat bones, vertebral bodies and epiphyses, and interior of diaphysis of long bones
330
Glycoprotein Family of Hormones
1. FSH
2. LH
3. TSH
4. Human Chorionic Gonadotropin (hCG)
331
Treatment use of Propanolol
β-adrenergic blocking drug useful in treating Hyperthyroid symptoms
332
Glucokinase vs Hexokinase
Glucokinase has lower affinity (high Km). Basically, active only when lots of glucose
333
GH Secretion Pattern
1. Secretory Pulses
| 2. Circadian Pattern
334
Metabolic Conditions Inhibiting GH Secretion
1. Hyperglycemia
| 2. Elevated Free FAs
335
Catecholamine Exocytosis Complex
Catecholamines are released in a complex with
1. ATP
2. Ca2+
3. Chromogranin
4. Other Peptides (ex: β-endorphin)
336
Principal Site of Insulin Degradation
Liver
337
Steroid Hormone Receptors when Bound
Form homodimers upon binding. Recruit Coactivator Protein complex (positive regulation) or Corepressor Protein to hormone binding site (negative regulation).
Binds Hormone Response Elements (HRE) on Promoter Region of target genes
338
Receptor Type: Thyroid Hormone Receptor
Ligand-Activated (Nuclear) Transcription Factor
339
Cortisol Effect on Glycogen Metabolism
Places permissive role. Induces the expression of Glycogen Synthase.
1. More glycogen formed in response to Insulin Stimulation (Glycogenesis)
2. Glucagon and Epinephrine have more substrate, therefore, permissive effect on Glycogenolysis too
340
Secondary Hypothyroidism and Causes
Result of Hypofunctional Pituitary Gland. Isolated TSH deficiency
Causes:
1. Infiltrative disorders
2. Surgery
3. Trauma
341
ED50
Concentration of hormone that produces half-maximal response; common measurement of sensitivity
342
Acute Effects of ACTH Release
1. Increased Hydrolysis of Stored Cholesterol Esters
2. Increased Synthesis of StAR
3. Increased Steroid Hormone Synthesis
4. Increased blood flow to Adrenal Cortex
343
Vitamin D Effects in Kidney
1. negative inhibition on Renal 1α-hydroxylase
| 2. Stimulates 24-hydroxylase
344
Mexedema
Generalized non-pitting edema in Hypothyroidism. Accumulation of Mucopolysaccharides in Connective Tissue spaces.
Symptoms:
1. Thickened skin/facial features
2. Enlarged tongue
3. Periorbital Edema
4. Hoarseness
5. Joint Stiffness
345
Counterregulatory Effects of Epinephrine
1. Inhibits glucose utilization by muscles
2. Stimulates Glycogenolysis
3. Stimulates Gluconeogenesis
4. Inhibits insulin secretion
5. Stimulates glucagon secretion
6. Stimulates lipolysis
346
Glycoprotein Hormone β Subunits
Unique for each protein
347
Required to detach Thyroglobulin from Colloid
Proteolysis of Thyroglobulin
348
Acyl-CoA Cholesterol Acyltransferase
Enzyme in the ER which converts Cholesterol to Cholesterol Esters for storage in Steroidogenic cells.
349
Hypophysiotropic Hormones with Gi Mechanism
1. Somatostatin
| 2. Dopamine
350
Enzyme converting Tyrosine to DOPA
Tyrosine Hydroxylase
351
Nervous System Effects of Thyroid Hormone
1. Promotes Axon/Dendrite Growth
2. Synapse Formation
3. Myelination
Absence leads to mental retardation. Effects learning, memory, responsiveness, wakefulness, etc.
352
Contained in Insulin Secretory Granule
Prohormone converting enzymes
353
Factors in Prenatal Growth
1. Maternal Genome (size/capacity of uterus)
2. Maternal Diet / Metabolism
3. Uterine Blood Flow
4. Maternal Environment (Behavioral)
5. Invasion of Endometrium by Trophoblasts (must be adequate)
6. Production of Hormones by Placenta
354
Aldosterone Synthase
Enzyme only found in the Zona Glomerulosa.
Converts DOC to Aldosterone.
355
Neurohypophysis
Posterior Pituitary
Composed of neural tissue, formed as downward evagination of floor of embryonic brain.
Direct hormone release into circulation
356
Components of Preprohormone Precursors of ADH and Oxytocin
1. Signal Peptide
2. Hormone Sequence
3. Neurophysin Domain
4. Glycopeptide Domain (ADH only)
357
Components of Serum IGF Complex
1. IGF
2. IGFBP-3
3. Acid-Labile Subunit (ALS)
Production of all stimulated by GH
358
Nutrients Stimulating Insulin Release
(in circulation)
1. Glucose
2. Amino Acids
359
Docking Site for Signaling Proteins in GH Receptor Pathway
Phosphotyrosine Residues on GH Receptor
360
Ketosis
Accumulation of ketone bodies in tissues and fluids due to production exceeding utilization.
High ketone levels can cause acidosis and toxic effects
Occurence:
1. Prolonged physical training
2. Starvation
3. Uncontrolled Diabetes (esp T1DM)
4. Keto diet
361
Cellular Level Influences of Thyroid Hormone
1. Tissue differentiation
2. Expression of key enzymes in metabolic pathways
3. Synthesis of several hormones
4. Responsiveness of target tissues to hormonal stimulatory effects
362
Insulin Receptor Substrates (IRS)
Major targets of insulin receptor tyrosine kinase activity. Multiple residues of IRS phosphorylated.
They serve as docking sites for other intracellular signaling proteins.
363
Lactotrope (Hypothalamic and Anterior Pituitary Hormones)
Hypothalamic Hormones:
1. Thyrotropin-Releasing Hormone (TRH) [++, Gq]
2. Dopamine [--, Gi]
Anterior Pituitary Hormone:
1. Prolactin (PRL)
364
Thyroid Hormone Binding Proteins
1. Thyroxine-Binding Globulin (TBH)
2. Transthyretin
3. Albumin
365
Transports Iodide from Follicle Cell to Lumen
Pendrin (Iodide-Chloride Exchanger)
366
Enzymes Require for Synthesis of Cortisol and Androgens
1. 17α-hydroxylase
2. 17,20-lyase
NOT FOUND IN ZONA GLOMERULOSA
367
Stimulates Erythropoetin Synthesis
Cortisol
368
C-Terminal Telopeptides of Type 1 Collagen (CTX)
Product of bone collagen degradation used as a marker of bone turnover
369
Insulin Effect on Muscle Protein
Skeletal Muscle
1. Stimulates AA uptake and protein synthesis
2. Inhibits proteolysis
370
Cortisol Effect on CNS
Mood, behavior, wakefulness, perception of stimuli affected by excess/deficiency
371
DOC as a Mineralocorticoid
Same affinity for receptor as Aldosterone. Also secreted at similar rate.
DOC has a high affinity for CBG, so it has a way smaller free fraction than aldosterone, therefore less effective
372
Human Chorionic Gonadotropin (hCG)
Placental Glycoprotein hormone.
* α subunit identical to FSH, LH, and TSH
* β subunit is same as LH plus an additional 32 AAs
373
Insulin Effects on Adipose Tissue
1. Stimulates glucose uptake
2. Stimulates Glycolysis
3. Induces synthesis of Lipoprotein Lipase (LPL)
4. Fatty Acid Uptake / Lipogenesis
5. Inhibitory effect on basal/hormonal Lipolysis
374
Enzyme Phosphorylating Glucose in Liver
Glucokinase
375
Conn Syndrome and Cause
Primary Aldosteronism (excessive secretion).
Cause is autonomous secretion of Aldosterone, usually by Adenoma in Zona Glomerulosa.
1. Mild Hypertension (Na, water retention)
2. Hypokaelmia
3. Metabolic Alkalosis (H+ secretion)
4. Plasma Renin depressed
376
STAT Proteins
Signaling protein in GH Receptor Mechanism. Have SH2 domain to recognize phosphotyrosine docking site on GH Receptor
Phosphorylated STAT proteins dimerize and activate gene transcription in the nucleus.
377
Goiter
Enlarged Thyroid gland
378
Steroidogenic Acute Regulatory Protein (StAR)
Facilitates movement of cholesterol from outer to inner mitochondrial membrane. Rate limiter in steroid hormone biogenesis. Very short half-life
Synthesis induced by cAMP-dependent mechanism.
379
Cortisol Effects on Catecholamine Release
Reaches medulla by way of Adrenal Cortex-Medulla portal system.
1. Induces PNMT
2. Prevents Chromaffin Cells from developing into Postganglionic Neurons
3. (also remember it has permissive effects elsewhere)
380
Most Common Thyroid Hormone in Circulation
T4 (60-70x greater than T3)
381
Dipeptidyl Peptidase 4 (DPP4)
Rapidly inactivates GIP and GLP-1
382
Mechanism of Reabsorption: Proximal Tubule
Passive Paracellular
383
Mechanism of Sympathetic Activation on Catecholamine Release
Preganglionic acetylcholine promotes release of stored granules. ACh binds to Nicotonic receptors promoting Na influx (depolarize). Voltage-gated Ca channels open.
Acetylcholine also promotes transcription of Tyrosine Hydroxylase
384
Hashimoto Thyroiditis
Autoimmune disease, antibodies react with Thyroid Peroxidase, Thyroglobulin, TSH Receptor. Gradually destroys Thyroid follicles.
Most common cause of Hypothyroidism in the US. More common with women and older age
385
Unique Feature of Lactotropes/Prolactin Release
Under tonic inhibition by Dopamine
386
Stimulate Transcription of StAR
1. Angiotensin II via Ca/Calmodulin mechanism (Zona Glomerulosa)
2. ACTH via cAMP mechanism (Zona Fasciculata/Reticularis)
387
Hormonal Regulators of Prenatal Growth
1. IGF-1/IGF-2 (independent of GH stimulation)
2. Insulin
3. Glucocorticoids
GH NOT major regulator
388
Principle component of a Colloid
Thyroglobulin (TG) -- a glycoprotein
389
Pheochromocytomas
Catecholamine-producing tumors of Chromaffin Cells of Adrenal Medulla (90%) or Extra-Adrenal Ganglia
Most Common Clinical Feature: Hypertension
390
Hormonal Regulators of Postnatal Growth
1. Growth Hormone (most important)
2. Thyroid Hormone
3. Sex Steroids
4. Insulin
5. Glucocorticoids
391
Phenylethanolamine-N-Methyltransferase (PNMT)
Converts Norepinephrine to Epinephrine in the cell cytoplasm after NE exists granule.
392
Thyroid-Stimulating Immunoglobulin (TSI)
Found in the serum during Graves Disease.
TSI binds to TSH receptor and induces similar effects
393
Hyperosmolar Hyperglycemia State (HHS)
1. Sever hyperglycemia
2. Hyperosmolality
3. Dehydration
394
Principal Counter-Regulatory Hormone
Glucagon (under normal conditions)
395
Somatotrope (Hypothalamic and Anterior Pituitary Hormones)
Most abundant cell type in Anterior Pituitary
Hypothalamic Hormones:
1. Growth Hormone-Releasing Hormone (GHRH) [++, Gs]
2. Somatostatin (SS) [--, Gi]
Anterior Pituitary Hormone:
1. Growth Hormone (GH)
396
Functions of Mineralocorticoids
1. Maintain Extracellular Fluid by regulating Na Reabsorption (Main)
2. Promote K+ Excretion
3. Promote H+ Excretion
397
Tertiary Hypothyroidism
Rare. Diminished TRH release. Damage to Hypothalamus
398
Adenohypophysis
Anterior Pituitary
Composed of epithelial tissue, formed as up-growth of Ectodermal Cells from roof of Embryonic Pharnyx.
Indirect hormone release via releasing-hormones
399
Mechanisms of Glucagon Promoted Gluconeogenesis
1. Increases Activity of Gluconeogenic Enzymes (via PKA)
2. Inhibits Glycolytic enzymes
3. Stimulates uptake of Amino Acids (esp Alanine)
400
Receptor Type: Steroid Hormone
Ligand-Activated Transcription Factors
401
Overview of Vitamin D Actions
1. Promotes Calcium Uptake by Small Intestine (Transcellular)
2. Promotes Pi Uptake by Small Intestines
3. Stimulates Bone Mineralization (indirect via Ca/Pi increase)
4. Negative feedback inhibition on Parathyroid land
5. Inhibits Renal 1α-hydroxylase activity
6. Stimulates 24-hydroxylase activity
402
Parasympathetic Nervous System Effect on Insulin Release
Vagal stimulation in presence of glucose promotes insulin release
403
Intracellular Mediator of Calcitonin Actions
cAMP
404
Proteins involved in Transcellular Reabsorption of Ca2+ (Ascending Limb of Loop)
1. TRPV5 **Important One**
2. Calbindin-D28k
3. PMCA
4. NCX
405
Principle Organic Molecule in Bone
Type 1 Collagen
406
GH and IGF-1 Levels: Starvation/Protein-Calorie Malnutrition
1. GH elevated
| 2. IGF-1 decreased (insulin necessary for max IGF-1 production by liver)
