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SF4 Exam 2 General Flashcards

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

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2
Q

Fate of Mature Osteoblasts

A
  1. 50-70% undergo apoptosis
  2. Lining Cells covering new bone
  3. Osteocytes
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3
Q

Cortisol Effects on Lipid Metabolism

A
  1. Induces synthesis of hormone sensitive lipase
  2. Enhances Epinephrine/GH stimulation of Lipolysis
  3. Promotes fat deposition (excess Cortisol via appetite)
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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

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5
Q

DIT + DIT

A

T4

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6
Q

Malonyl CoA

A

Blocks entrance of Fatty Acids into Mitochondria

  • Increased by Insulin
  • Decreased by Glucagon
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7
Q

Converts Dopamine to Norepinephrine within Secretory Granule

A

DBH

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8
Q

Layers of Adrenal Gland by Primary Secretion

A

Adrenal Cortex:

  1. Zona Glomerulosa – Aldosterone
  2. Zona Fasciulata – Glucocorticoids
  3. Zona Reticularis – Androgens

Adrenal Medulla: Catecholamines

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9
Q

Transports Iodide from Blood to Thyroid Gland

A

Na/I Symporter (NIS)

Utilizes gradient created by Na/K-ATPase

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10
Q

Major Source of IGF-1

A

Liver

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11
Q

Thyroid-Associated Opthalmopathy

A

Sign of Thyrotoxicosis assocciated typically with Graves Disease but also other Thyrotoxicosis

Characteristics:

  1. Periorbital Edema
  2. Proptosis (Graves Specific; not from TH)
  3. Lid Retraction (Other forms of Thyrotoxicosis too)
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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

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13
Q

Physiological Roles of Iodothyronine Deiodinases

A
  1. Maintain circulating pool of T3
  2. Local regulation of T3 production (target tissue)
  3. Thyroid Hormone Inactivation
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14
Q

Cell converting Proglucagon into Glucagon

A

Pancreatic α Cells

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15
Q

Chronic Effects of ACTH Release

A
  1. Increased Growth/Cell Prolif. in Zona Fasciculata and Reticularis
  2. Increased Synthesis of Steroidogenic enzymes, LDL receptors, Other proteins
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16
Q

DNA Sequence THRs bind to

A

Thyroid Hormone Response Elements (TREs)

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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)

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18
Q

Decrease IGFBP Affinity for IGF1

A
  1. Binding to target cells

2. Degradation by IGFBP Proteases

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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

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20
Q

Provide Docking Sites in IGF-1 Receptor Pathway

A
  1. Phosphotyrosines on Receptor

2. Insulin Receptor Substrate-1 (IRS-1)

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21
Q

Products of Proinsulin Cleavage

A
  1. Insulin

2. C Peptide

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22
Q

Promotes Fatty Acid Synthesis in Liver

A

Insulin

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23
Q

ACTH Receptor in Adrenal Cortex

A

Melanocortin-2 Receptor (MC2R)

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24
Q

Inhibits OPG Production

A

PTH

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25
Q

Metabolic Processes Suppressed by GH

A
  1. Glucose Uptake & Oxidation

2. Protein Breakdown (Fed State)

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26
Q

Nuclear Localization Signal

A

Domain on Steroid Hormone receptors allowing it reside in nucleus or translocate to the nucleus when activated

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27
Q

Incretin Defect in T2DM

A

Incretin secretion intact; β cell response is impaired

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28
Q

Inhibits RANK-L Expression

A

Estradiol

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29
Q

Insulin Receptor

A

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

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30
Q

Increases Glucokinase expression

A

Insulin

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31
Q

Mechanism of Reabsorption: Distal Convoluted Tubules

A

Transcellular (Saturable Active Transport)

Regulated by PTH (TRPV5)

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32
Q

Enzyme necessary to export glucose after gluconeogenesis

A

Glucose 6-phosphatase

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33
Q

Cause of Hyperinsulinemia

A

GH Excess

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34
Q

Glucose Transporter in β Cells

A

GLUT2

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35
Q

Matrix Digestion Products from Bone Resorption

A

Serve as markers in serum/urine

  1. CTX (C-Terminal Telopeptides of Type 1 Collagen)
  2. NTX (N-Terminal Telopeptides of Type 1 Collagen)
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36
Q

Mechanism for Genes Repressed by T3 Binding

A
  1. Transcription is stimulated in the absence of T3/THR

2. T3/THR bind to negative TRE to repress transcription

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37
Q

Iodothyronines

A
  1. Thyroxine (T4)
  2. Triiodothyronine (T3)
  3. Reverse T3 (rT3)
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38
Q

Calcium-Sensing Receptors (CaSR)

A

G-protein coupled receptor on Chief Cells. Monitor changes in Serum Ca.

Gi: Inhibit Adenylyl Cyclase
Gq: Activate Phospholipase C

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39
Q

Action: Phosphorylase Kinase and Inhibitor 1

A

Induce conversion of Phosphorylase b to Phosphorylase a, promoting Glycogenolysis

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40
Q

Precursor of Glucagon

A

Preproglucagon

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41
Q

Major Organ Involved in Calcium Homeostasis

A

1) Skeleton
2) Small Intestine
3) Kidneys
4) Parathyroid Glands

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42
Q

Enzyme Phosphorylating Glucose in β Cells

A

Glucokinase

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43
Q

Indicator of Daily Cortisol Output

A

24-hour urinary excretion of unmetabolized cortisol (even though 99% of urinary cortisol is metabolized)

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44
Q

Principal Targets of Insulin

A
  1. Liver
  2. Skeletal Muscle
  3. Adipose Tissue
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45
Q

GH Excess in Adulthood

A

Acromegaly

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46
Q

Serine Phosphorylation and Insulin

A
  1. Reduce signal intensity by serine phosphorylation on Insulin Receptor
  2. Phosphorylation of IRS proteins has inhibitory effect on transduction
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47
Q

Thyroid Hormone effects on Growth Hormone

A
  1. Synergistic/Permissive effect on action of Growth Hormone and others
  2. Stimulates Growth Hormone synthesis/release at Pituitary Gland
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48
Q

Rate-Limiting Step in Steroid Biogenesis

A

Transfer of Cholesterol to Inner Mitochondrial Membrane. See StAR protein

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49
Q

Cortisol Effects on Carbohydrate Metabolism

A
  1. Prevents Hypoglycemia
  2. Promotes Hepatic Gluconeogenesis
  3. Permissive Effect on Glycogen Formation
  4. Decrease GLUT-4 Translocation
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50
Q

Functions of IGF Binding Proteins (IGFBP)

A
  1. Provide circulating reserve of IGF
  2. Increase half-life of IGF
  3. Modulate bioavailability
  4. Potentiate/Inhibit IGF action
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51
Q

Mechanism of H+ Secretion by Osteoclasts

A

Membrane-Associated H+-ATPase. Dissolves Hydroxyapatite crystals in bone matrix

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52
Q

Catecholamine Transport in Blood

A
  1. Albumin (59%)

2. Free Catecholamines

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53
Q

Clinical markers of Hashimoto Thyroidits

A
  1. Anti-TPO antibodies

2. Anti-TG Antibodies

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54
Q

Signaling Pathway Activated by IGF-1

A

Ras/Map Kinase Pathway

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55
Q

PI-3 Kinase / Akt Signal Transduction Pathway

A

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

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56
Q

Causes of Hypoglycemia

A
  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
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57
Q

Effects of IGF-1 Binding

A
  1. Stimulation of DNA, RNA and Protein Synthesis
  2. Cell Proliferation
  3. Insulin-like Effects on Adipose/Muscle Cells
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58
Q

(Adrenal) Medullary Plexus

A

Former from merging of Medullary Arterioles and Cortical Sinusoids

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59
Q

Lid Retraction

A

Occurs in Thyrotoxicosis due to over-activity of Sympathetic Nervous System. Not just in Graves Disease but other Thyrotoxicosis

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60
Q

Cushing Syndrome and Causes (ordered by importance)

A

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
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61
Q

Secondary Aldosteronism

A

Caused by inappropriate activation of Renin-Angiotensin System

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62
Q

Glucose Transporter in Skeletal Muscle

A

GLUT4

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63
Q

Mechanism of Matrix Protein Digestion by Osteoclasts

A

Cathepsin K (Protease) secretion

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64
Q

Innervation of Adrenal Medulla

A

Cholinergic Preganglionic Fibers

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65
Q

24,25(OH)2D

A

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

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66
Q

Insulin Effects on Carbohydrate Metabolism in Liver

A
  1. Promotes Glycogen Storage
  2. Promote Glycolysis
  3. Inhibits Glycogenolysis
  4. Prevents Release of Glucose
  5. Inhibits Gluconeogenesis
  6. Stimulates Fatty Acid Synthesis
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67
Q

Endemic Gioter

A

Low iodide intake common in third wold countries. Decreased Thyroid Hormone production leads to increased TSH output

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68
Q

Secondary Adrenocortical Insufficiency and Causes

A

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

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69
Q

Stimulates Production of IGF-Binding Proteins in the Liver

A

Growth Hormone

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70
Q

Definition: Sensitivity

A

Ability of target cell to recognize and respond to hormone in proportion to intensity of signal

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71
Q

Affect Circulating TBG Levels

A
  1. Malnutrition
  2. Liver/Kidney Disease
  3. Synthesis Stimulated by Estrogens
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72
Q

Mechanism of Reabsorption: Ascending Limb, Loop of Henle

A

Passive Paracellular and Transcellular

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73
Q

Phosphate Uptake in Small Intestine

A

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

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74
Q

Location of Magnocellular Cells

A

Supraoptic and Paraventricular Nuclei (Hypothalamus)

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75
Q

TRPV5

A

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.

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76
Q

Anions Competing for Sites on NIS

A
  1. Perchlorate (HCLO4-)
  2. Thiocyanate (CNS-)
  3. Pertechnetate (TcO4-)
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77
Q

Lipoprotein Lipase

A

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

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78
Q

Primary Hypothyroidism and Causes

A

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
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79
Q

P450c17

A

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.

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80
Q

Adrenocorticotropic Hormone Precursor found in all three zones of the Adrenal Cortex

A

All three can synthesis pregnenolone and progesterone from cholsterol

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81
Q

Clinical indicator of Adrenal Androgen Release

A

DHEA and DHEAS in plasma

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82
Q

Thyroid Hormone Levels during Fast

A
  1. T4 levels remain constant

2. T3 drops due to decrease in T4->T3 conversion

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83
Q

Bigger Effect: Thyroid Hormone Negative Feedback on Hypothalamus or Pituitary Gland?

A

Pituitary Gland

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84
Q

Definition: Threshold

A

Minimum concentration to produce detectable response

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85
Q

Release Pattern of Thyroid-Stimulating Hormone

A

Pulsatile with Circadian Pattern. Higher late in evening

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86
Q

Principal Regulator of PTH Secretion

A

Concentration of ionic calcium in Extracellular Fluid (Chief cells are very sensitive to 2-3% deviations)

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87
Q

Intracellular Mechanism of GHRH Binding

A

G protein activation of Adenylyl Cyclase. cAMP/PKA mechanism activates voltage-gated Ca2+ channels.

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88
Q

Mechanism for Genes Activated by T3 Binding

A
  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
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89
Q

Physiological Stimuli of GH Release

A
  1. Exercise
  2. Stress
  3. Sleep
  4. Postprandial Hypoglycemia
  5. Protein Rich Meal / IV infusion (Arginine esp)
  6. Sex Steroids
  7. Ghrelin
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90
Q

Apical membrane Calcium Channels in Small Intestine

A
  1. TRPV6
  2. TRPV5

Synthesis increased by Vitamin D3

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91
Q

Anti-Inflammatory Effects of Cortisol

A
  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
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92
Q

Primary Cause of Growth Hormone Excess

A

Pituitary Adenoma

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93
Q

Rate-Limited Step in Catecholamine Synthesis

A

Conversion of Tyrosine to DOPA by Tyrosine Hydroxylase

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94
Q

Cell Type Secreting PTH

A

Chief Cells

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95
Q

Trigger of Calcitonin Secretion

A
  1. Plasma Ca rising above 9 mg/dL

2. Gastrin (supraphysiological levels)

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96
Q

Somatomammotropin Family of Hormones

A

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)
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97
Q

Dissociation Constant

A

Concentration when 1/2 of receptors occupied; Kd = [H] and also 1/Ka

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98
Q

Primary Source of Norepinephrine in Circulation

A

Nerve terminals

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99
Q

Release Structures for Anterior Pituitary Gland Secretion

A
  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
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100
Q

Principal Adrenal Androgen Released by Zona Reticularis

A

Dehydroepiandrosterone (DHEA). Primarily released as DHEA Sulfate (DHEAS)

Also small amounts of Androstenedione

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101
Q

Multiple blood samples of this hormone are taken at timed intervals and combined to test levels

A

Integrated GH Concentration

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102
Q

Mechanisms of Calcium Uptake in Small Intestines

A

Transcellular (affected by Vitamin D) and Paracellular

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103
Q

Paracrine Regulator in Pancreas Inhibiting Insulin and Glucagon Release

A

Somatostatin

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104
Q

Metabolic Processes Stimulated by GH

A
  1. Lipolysis (esp. Visceral fat)
  2. Gluconeogenesis
  3. Glycogenolysis
  4. Protein Production (Fed State)
  5. Pancreatic Cell Growth / Function
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105
Q

Cell converting Proglucagon to GLP-1, GLP-2

A

Intestinal L Cells

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106
Q

Fasting Actions of Glucagon

A
  1. Stimulates Glycogenolysis
  2. Inhibits Glycogen Synthase
  3. Inhibits Glycolysis
  4. Promote Glucogenesis
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107
Q

Location of Thyroid Gland

A

Two lobes either side of the trachea, below the Larynx

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108
Q

Summary of PTH Effects:

A
  1. Stimulates Calcium Reabsorption
  2. Stimulates Phosphate Excretion
  3. Stimulates Vitamin D Synthesis
  • Serum/Urine Calcium: Increases
  • Serum Phosphate: Decreases
  • Urine Phosphate: Increases
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109
Q

Adrenal Hormone whose main stimulator is not ACTH

A

Aldosterone (Angiotensin II and K to lesser degree)

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110
Q

Prolongs lifespan of Osteoclasts

A

RANK/RANK-L system inhibits apoptosis in Osteoclasts

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111
Q

Steroid Hormone Transport in Blood

A
  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
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112
Q

Intracellular Mechanism: β1,2,3-adrenergic receptors

A

increased cAMP

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113
Q

Hepatic Glycogenolysis

A

Mobilizes glycogen into glucose. Action mediated by cAMP

PKA Phosphorylates:

  1. Phosphorylase Kinase (activate)
  2. Inhibitor 1 (activate)
  3. Pathway inhibiting Glycogen Synthase Activity
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114
Q

Alkaline Phosphatase

A

Diffuse into blood and used as indicator of bone formation.

Levels elevated during childhood growth, following major fracture, and in certain bone destroying disease.

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115
Q

Transports Epinephrine back into Secretory Granule after conversion from NE

A

VMAT (again)

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116
Q

Mechanism to Regulate Quantity of PTH Released

A

Degradation of stored PTH in Secretory Vesicles. Increase in release of inactive C-terminal fragments when PTH not needed

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117
Q

Neuroglycopenia

A

Deficient supply of glucose to CNS

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118
Q

Precursor of Insulin

A

Proinsulin

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119
Q

P450scc

A

Side-chain cleave enzyme which converts Cholesterol to Pregnenolone.

Located in Inner Mitochondrial Membrane

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120
Q

Factors Controlling Osteoblast Growth/Differentiation

A
  1. Bone Morphogenic Proteins
  2. Growth Factors (ex: IGF-1)
  3. Cytokines (ex: Interleukins 1 and 6)
  4. Mechanical Forces
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121
Q

Propylthiouracil

A

Blocks iodination of Thyroglobulin and inhibits conversion of T4 to T3.

Antithyroid drug which could the cause of Primary Hypothyroidism

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122
Q

Humoral Hypercalcemia of Malignancy (HHM)

A

Tumors release humoral agents into circulation promoting resorption. Associated with a variety of malignant tumors.

PTHrP is the most common mediator

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123
Q

Causes of Symptoms of Hypoglycemia

A
  1. Sympathetic Activation

2. Neurogylcopenia

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124
Q

Neurons releasing Hypophysiotropic Hormones

A

Parvicellular Neurons (Hypothalamus)

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125
Q

Corticotrope (Hypothalamic and Anterior Pituitary Hormones)

A

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)
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126
Q

Diabetic Ketoacidosis

A

First indicator in children/adolescents with T1DM (not always.

  1. Uncontrolled hyperglycemia
  2. Metabolic acidosis
  3. ketosis
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127
Q

Serious Acute Complications in T1DM

A
  1. Diabetic Ketoacidosis

2. Hyperosmolar Hyperglycemic State (HHS)

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128
Q

PTH Effect on Vitamin D Metabolism

A

Induces 1α-renal hydroxylase activity in the Proximal Tubules (conversion of 25(OH)D3 to 1,25(OH)2D3)

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129
Q

Organification of Thyroglobulin

A

Binding of Oxidized Iodide to Thyroglobulin

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130
Q

Hormone Abnormality leads to Hypercholsterolemia

A

Hypothyroidism

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131
Q

Phospholipase A2

A

Catalyzes synthesis of inflammatory agents such as Prostaglandins, Thromboxanes, and Leukotrienes from Arachidonic Acid

Synthesis inhibited by Cortisol

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132
Q

Stimulates RANK-L Expression

A

PTH

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133
Q

Test Most Commonly Used when Endocrine Gland Hyperfunctional

A

Suppression Test

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134
Q

Cells Secreting Catecholamines into Blood Stream

A

Chromaffin Cells

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135
Q

Enzyme Hydroxylating 25(OH)D to 1,25(OH)2D

A

Renal 1α-hydroxylase

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136
Q

Action of Thyroid Hormone in Prolonged Fast

A

15-20% decrease in basal metabolic rate

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137
Q

Wolff-Chaikoff Effect

A

Thyroid Gland Autoregulation.

Ingestion of excessive amounts of iodine suppresses thyroid hormone synthesis. Suppresses expression of NIS and Thyroid Peroxidase.

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138
Q

Type of Neurons Posterior Pituitary Gland Axons Originate from

A

Unmyelinated axons from Magnocellular Neurons

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139
Q

Definition: Maximum Response

A

Effect produced by a saturating concentration of hormone

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140
Q

Neurophysin Domain

A

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.

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141
Q

Bone Resorption Initiation

A

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
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142
Q

Cell Secreting Calcitonin

A

Parafollicular Cells (C Cells of Thyroid)

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143
Q

Effects of Chronically-Elevated Insulin Levels (on Insulin Receptors)

A
  1. Increased rate of receptor-mediated endocytosis

2. Decreases rate of Insulin Receptor synthesis

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144
Q

Blood Transport of Glucocorticoids

A
  1. Corticosteroid Binding Globulin (CBG) (75%)
  2. Albumin (15%)
  3. Free Cortisol
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145
Q

Steroid Hormone Receptors when Unoccupied

A

Form complexes with Chaperone Proteins (Heat-Shock Proteins). When steroid binds it dissociates.

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146
Q

Conversion Products of DHEA and Androstenedione Peripherally

A
  1. Testosterone

2. Dihydrotestosterone

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147
Q

Gonadotrope (Hypothalamic and Anterior Pituitary Hormones)

A

Hypothalamic Hormone:
1. Gonadotropin-Releasing Hormone (GnRH) [++, Gq]

Anterior Pituitary Hormone:

  1. Follicle Stimulating Hormone (FSH)
  2. Lutenizing Hormone (LH)
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148
Q

Majority Source of Circulating T3 and rT3

A

Peripheral Metabolism of T4

Especially: Liver and Kidney

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149
Q

Stimulates OPG Production

A

Estradiol

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150
Q

Thyroid Hormone Effects on Metabolism

A

Potentiates Catecholamine Effects on:

  1. Lipolysis
  2. Glycogenolysis
  3. Gluconeogenesis

Likely by β-adrenergic receptor upregulation

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151
Q

Catalytic Activity of GH Receptor

A

No intrinsic activity; relies on Janus Kinases (JAK2)

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152
Q

Main IGF Binding Protein

A

IGFBP-3

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153
Q

How are the two forms of Growth Hormone produced

A

Differential splicing of mRNA

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154
Q

Thyroid Hormone Negative Feedback

A

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
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155
Q

Mediators of Glucagon Release during Hypoglycemia

A
  1. Sympathetic Stimulation

2. Rise in Circulating Catecholamines (β2 receptor)

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156
Q

Sympathetic Nervous System Effect on Insulin Release

A

Exercise and stress inhibit insulin release.

Mediated by α2-adrenergic receptors coupled to Gi protein

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157
Q

Promotes Transcription of Tyrosine Hydroxylase

A

Acetlycholine

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158
Q

Adrenal Hormones with Negative Feedback Inhibition of ACTH Release

A

Only Cortisol.

Androgens and Aldosterone do not.

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159
Q

Compact Bone

A

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.

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160
Q

Primary Target of Glucagon

A

Liver

  1. Glycogenolysis
  2. Gluconeogenesis
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161
Q

Non-Autoimmune Causes of Thyrotoxicosis

A

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
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162
Q

Paracrine Suppressors of Glucagon

A

Insulin and Somatostatin

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163
Q

Increases the half-life of Glycoprotein Hormones

A

Glycosylation of the protein after the subunits are combined.

164
Q

Principal Substrates for Hepatic Gluconeogenesis

A
  1. Amino Acids from Skeletal Muscle
  2. Lactate from Skeletal Muscle and RBCs
  3. Glycerol from Fat
165
Q

Counterregulatory Effects of Growth Hormone and Cortisol

A

Released in Anterior Pituitary after Hypothalamic Releasing Hormones released in response to Hypoglycemia.

Slow acting, not important in acute but instead prolonged Hypoglycemia

166
Q

Transcription Factors Activated by PKA upon GHRH

A
  1. GH

2. GHRH Receptor

167
Q

Enhances GH release stimulated by GHRH

168
Q

Mechanism for Ca Crossing Basolateral Membrane in Small Intestines

A

Calcium ATPase (PMCA)

169
Q

Synthetic Glucocorticoids

A

Enhanced activity due to increased affinity for receptor and delayed clearance.

  1. Dexamethasone
  2. Prednisone
170
Q

Number of Parathyroid Glands

171
Q

Vitamin D Effects on Parathyroid Gland

A

Negative feedback on PTH secretion

  1. Inhibits PTH gene
  2. Induces expression of CaSR
  3. Induces expression of Vitamin D Receptor (VDR)
172
Q

RANK

A

Receptor expressed on OsteoClast precursors. Binds RANK-L

Turns on signaling pathways in the OsteoClast precursors, promoting differentiation and fusion into multinucleated cells.

173
Q

Association Constant Formula

A

Ka = [HR] / [H][R]

174
Q

Cells in Epiphyseal Growth Plate Expressing Both GH and IGF-1 Receptors

A

Chondrocytes

175
Q

Hypophysiotropic Hormones with Gq Mechanism

A
  1. TRH
  2. GnRH
  3. AVP
176
Q

Effects of Chronic TSH Stimulation

A
  1. Growth of Thyroid Gland

2. Capillary Proliferation

177
Q

Catalyzes MIT and DIT Coupling

A

Thyroid Peroxidase

178
Q

Mechanism of Vitamin D Receptor (VDR)

A

Functions as a ligand-activated transcription factor

179
Q

Incretins

A

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
Q

Decreased Thyroid Hormone Binding Affinity to TBG

A

Salicylates

181
Q

Induces Aldosteron Synthesis by Activating Voltage-Gated Ca2+ Channels

182
Q

Steroid Hormone Receptor Antagonist

A

Binds to receptor, inducing conformation change that prevents coactivators from binding and/or favors corepressor binding to receptor

183
Q

Growth Hormone Carrier in Blood

A

GH Binding Protein (same structure as external portion of receptor)

184
Q

Thyrotoxicosis

A

Clinical syndrome characterized by Thyroid hormone excess. Symptoms result from:

  1. Increased metabolic activity
  2. Increased catecholamine sensitivity
185
Q

Sulfonylureas

A

Oral hypoglycemic drug used to treat T2DM.

Binds to SUR subunit of ATP-Gated K+ Channels in β cells, closing channel

186
Q

Glucose Transporter in Adipose Tissue

187
Q

Limits Substrate Availability for Gluconeogenesis

188
Q

Intracellular Mechanism: α1-adrenergic receptor

A

Increased IP3, Ca, DG

189
Q

Osteocytes

A

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
Q

Enzymes involved in Intraglandular Degradation of PTH

A

Secretory Vesicle Proteases. Degrade intact PTH into inactive C-terminal fragments

191
Q

Blood Transport of Mineralocortiocoids

A
  1. No specific aldosterone-binding globulin
  2. Weakly binds Corticosteroid-Binding Globulin (CBG)
  3. Albumin (most aldosterone)
  4. Free Aldosterone (40-50%)
192
Q

Release of Free Cholesterol in Steroidogenic Cells

A

LDLs enter the cell via endocytosis. They undergo hydrolysis in the lysosomal compartment to release the free cholesterol

193
Q

Axis-Driven Feedback Loops

A

Tropic hormones can inhibit their own release, so can the final product

194
Q

Action of Fetal Adrenal Gland

A

Produces large amounts of DHEA Sulfate (inner fetal zone; neocortex largely predifferentiated)

DHEAS converted to Estrogens by the Placenta

195
Q

ACTH Regulation of Adrenal Androgen secretion

A

ACTH stimulates Adrenal Gland but does not increase during Adrenarche

196
Q

Thyroid Hormone Effect on Cardiac Output

A

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
Q

Pharmacological Iodide doses treat..

A

Acute Thyrotoxicosis

198
Q

Primary Source of Epinephrine in Circulation

A

Adrenal Medulla (only source)

199
Q

Layers of Adrenal Cortex (Superficial to Deep)

A
  1. Zona Glomerulosa
  2. Zona Fasciulata
  3. Zona Reticularis
200
Q

Thyrotrope (Hypothalamic and Anterior Pituitary Hormones)

A

Hypothalamic Hormone:
1. Thyrotropin-Releasing Hormone (TRH) [++, Gq]

Anterior Pituitary Hormone:
1. Thyroid Stimulating Hormone (TSH)

201
Q

Clinically Measured to Assess Vitamin D Status

A

25-hydroxyvitamin D [25(OH)D]

202
Q

Causes of Congenital Hypothyroidism

A
  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
Q

Cholesterol Esterase

A

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
Q

Congenital Adrenal Hyperplasia (CAH) and Causes

A

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
Q

Shift Right or Left – Decrease in Sensitivity (Concentration-Response Curve)

A

Shift to Right

206
Q

NADPH Oxidase

A

Generates H202 (hydrogen peroxide) in Follciular Lumen, which then acts as an electron acceptor in the Oxidation of Iodide

207
Q

Mineralocorticoids

A
  1. Aldosterone
  2. DOC
  3. Cortisol (has activity but its a Glucocorticoid)
208
Q

Release Structure for Posterior Pituitary Gland Secretion

A

Infundibulum

209
Q

Stimulation test for Prolactin

210
Q

Hormone for which you would do Arginine Infusion stimulation test

A

Growth Hormone

211
Q

Endocrine Cell Clusters in Pancreas

A

Islets of Langerhans

212
Q

Intracellular Calcium Binding Protein (Small Intestine)

A

Calbindin-D9k

Protects cell against cytotoxic effects of elevated calcium. Maintains the gradient for influx.

Synthesis increased by Vitamin D3.

213
Q

Ruffled Border

A

Elaborate membrane structures formed on Osteoclast-sealed areas of contact with bone

Secrete hydrogen ions onto bone surface

214
Q

Principal Precursor for Steroidogenesis

A

Low-Density Lipoprotein (LDL)

Remainder from other lipoproteins or de novo synthesis from Acetate

215
Q

PKB/Akt

A

Part of Insulin effects and Pi-3 Kinase / Akt Pathway.

Initiates signaling cascade promoting translocation of GLUT4 to membrane.

216
Q

Intracellular Mechanism of Somatostatin Binding (Pituitary Gland)

A
  1. Inhibition of Adenylyl Cycle

2. Activation of K+ channels (hyperpolarizing)

217
Q

11β-Hydroxysteroid Dehydrogenase 2 (11β-HSD2)

A

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
Q

Contained in Follicle Lumen

219
Q

Principal Carrier of Vitamin D in Blood

A

Vitamin D Binding Globulin (DBG)

220
Q

Thyroid Hormones in Postnatal Growth

A

Required for normal growth but will not promote growth without GH. Promotes linear growth by increasing GH secretion.

221
Q

Laron Dwarfism

A

High GH levels but IGF not produced in Response

Type 1: Deletions/mutations in GH Receptor gene

Type 2: Post-GH Receptor Defect

222
Q

Cholecalciferol / Vitamin D3

A

Formed from the reaction of 7-dehydrocholesterol with UV light in the skin

223
Q

MIT + DIT

224
Q

Ergocalciferol / Vitamin D2

A

Vitamin consumed in diet from plant sterol reaction with ultraviolet.

225
Q

Products of Oxidized Iodide Binding to Thyroglobulin

A
  1. Monoiodotyrosine (MIT)

2. Diiodotyrosine (DIT)

226
Q

Cell Secreting Calcitonin

A

Parafollicular (C Cells) of Thyroid

227
Q

Proptosis

A

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
Q

Stimulates Alveolar Maturation and Surfactant Production in Development

229
Q

Insulin Effect on Ketogenesis

A
  • Direct: Stimulates formation of Malonyl CoA, which blocks transport of fatty acids into the Mitochondria
  • Indirect: Decreases FAs in circulation by inhibiting Lipolysis
230
Q

Myxedema Coma

A

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
Q

Receptor Type: IGF-1 Receptor

A

Receptor Tyrosine Kinase

232
Q

Depolarizes β Cell during Insulin Secretion

A

ATP-Gated K+ Channel

ATP binds to channel and inhibits K+ efflux

233
Q

Osteoprotegerin (OPG)

A

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
Q

Hormones Released from Posterior Pituitary Gland

A
  1. ADH (Vasopressin)

2. Oxytocin

235
Q

Hormones Indirectly Stimulating Insulin Release Because Action Antagonizes Insulin

A
  1. GH

2. Cortisol

236
Q

Site of Cleavage of Prepro-PTH

A

Trans-Golgi Network

237
Q

Exhibits symptoms of Hypothyroidism. Patients have elevated MIT and DIT in serum and Urine.

A

Microsomal Iodotyrosine Deiodinase Deficiency

238
Q

Osteomalacia

A

Vitamin D deficiency impairing bone mineralization AFTER EPIPHYSEAL PLATE CLOSES

239
Q

Majority Source of Circulating T4

A

All from Thyroid

240
Q

25-hydroxyvitamin D [25(OH)D]

A

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
Q

Cortisol Effect on Cardiovascular System

A

Require for response to Vasoconstrictors (Catecholamines and Angiotensin II)

242
Q

Addison Disease and causes

A

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
Q

Androgen effect on Skeletal Growth

A

Increases thickness of cortical bone by stimulating Periosteal Bone Expansion

244
Q

PTH Actions on Bone

A

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
Q

Function of Calcitonin

A

Major: Suppress bone resorption by Osteoclasts

Secondary: Increase calcium clearance

246
Q

PTH Effects on Phosphate Balance

A

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
Q

Major Cause of Hypoparathyroidism

A

Autoimmune disorder and inadvertent removal of glands during surgery

248
Q

Rickets

A

Vitamin D deficiency impairing bone mineralization IN GROWING BONES

249
Q

7-dehydrocholsterol

A

Vitamin D precursor found in skin

250
Q

Principal Extrinsic Regulator of Postnatal Growth

251
Q

Deoiodinate MIT and DIT remaining in cell after Thyroid Hormone Secretion

A

Microsomal Iodotyrosine Deiodinase

252
Q

Catecholamine-Degrading Enzymes

A
  1. Monoamine Oxidase (MAO)

2. Catecholamine-o-Methyltransferase (COMT)

253
Q

Binding Site of Oxidized Iodide on Thyroglobulin

A

Tyrosyl residue

254
Q

Site of Conversion of DOC to Corticosterone in Zona Fasciculata

A

Mitochondria via 11β-hydroxylase

255
Q

Hypophysiotropic Hormones with Gs Mechanism

A
  1. CRH

2. CHRH

256
Q

Trousseau’s Sign

A

Hypoparathyroidism. Tetany in hand happens first, when serum calcium falls to 6 mg/dL

257
Q

Glycoprotein Hormone α Subunits

A

All identical (single gene)

258
Q

Absorptive State

A

Period of time during and after ingestion of meal when cell metabolism fueled primarily by nutrients absorbed from meal. Lasts about four hours

259
Q

Examples of Genes Repressed by T3/THR binding to TRE

A
  1. Thyrotropin-Releasing Hormone Receptor

2. TSH Subunits

260
Q

Fundamental Difference Between Thyroid and Steroid Hormone Receptors

A

Thyroid Hormone Receptors can bind DNA when receptor occupied or unoccupied.

Steroid Hormone Receptor have to be occupied to bind DNA.

261
Q

Paracrine Regulator in Pancreas Stimaulating Insulin Release

262
Q

11β-Hydroxysteroid Dehydrogenase 1 (11β-HSD1)

A

Converts Cortisone to Cortisol (reversible).

Expressed in tissues with Glucocorticoid Receptors (liver, skin, adipose tissue, CNS)

263
Q

Symptoms: Hypoparathyroidism

A

Clinical features due to hypocalcemia.

  1. Neuronal membranes more permeable and excitable
  2. Tetany from spontaneous discharge of peripheral nerves
264
Q

Proopiomelanocortin Family of Hormones

A

Single gene precursor: Proopiomelanocortin (POMC)

Most Important Cleavage Product: ACTH

265
Q

ACTH/Cortisol Release Patterns

A

Secretory pulses throughout day (7-13/day).

Cortisol release in Diurnal Rhythm, highest in morning when sleep-wake/light-dark cycles synchronized

266
Q

Parathyroid Hormone Receptor 1 (PTH/PTHrP Receptor)

A

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
Q

Release Pattern of Insulin

268
Q

Degradation and Excretion of Steroid Hormones

A

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
Q

Macrophage Colony Stimulating Factor (M-CSF)

A

Promotes early differentiation of Monocyte/Macrophage lineage cells. Works with RANK-L to promote OsteoClastogenesis

Secreted by Osteoblast Lineage Cells

270
Q

Normal Plasma Range for Calcium

A

8.5 - 10.3 mg/dL

271
Q

Direct Effect of Hyperparathyroidism

A

Bone lesions (PTH-induced bone resorption)

272
Q

Promotes Substrate Availability for Gluconeogenesis

273
Q

Metabolites of Catecholamine Inactivation

A
  1. Metanephrines

2. Vanillylmandelic Acid

274
Q

Acute vs Hours/Days vs Prolonged Hypocalcemia Responses

A

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
Q

Proteins of Bone Matrix formed by Osteoblasts

A
  1. Type 1 Collagen
  2. Alkaline Phosphatase
  3. Osteopontin
  4. Osteocalcin
  5. Bone Sialoprotein
276
Q

First Step in Steroid Hormone Biogenesis

A

Conversion of Cholesterol to Pregnenolone by P450scc

277
Q

Endocrine Glands Secreting Steroid Horomones

A
  1. Adrenal Cortex
  2. Testes
  3. Ovaries
  4. Placenta
278
Q

Functions of Insulin

A
  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
Q

Brain’s Response to Hypoglycemia

A
  1. Hypothalamus activates Sympathetics
  2. Sympathetics act on Pancreatic Islets to stimulate glucagon and inhibit insulin release
  3. Rapid rise in circulating Epinephrine
280
Q

Arachidonic Acid Metabolite Promoting Intraglandular Degradation of PTH

A

Leukotrienes. Activated in Arachidonic Acid Pathway by CaSR Gq protein

281
Q

90% of filtered calcium reabsorbed in the…

A

Proximal Convoluted Tubule and Thick Ascending Limb of Loop of Henle

282
Q

TREs can form monomers, homodimers, or heterodimers with other Nuclear Receptor family members when binding DNA. Which combination has the highest binding affinity?

A

Heterodimer of:

  1. T3 / THR
  2. Retinoid X Receptor (RXR)
283
Q

Mechanism for Insulin repression of Gluconeogenesis

A
  1. Suppresses expression of Gluconeogenic enzymes

2. Inhibits protein catabolism (substrate)

284
Q

Triggers Release of Insulin via Exocytosis

A

Voltage-Gated Ca2+ channels

285
Q

Test Most Commonly Used when Endocrine Gland Hypofunctional

A

Stimulation Test

286
Q

Receptor Tyrosine Phosphatases

A

Dephosphorylate Insulin-Receptor complexes after endocytosis

287
Q

Anti-Inflammatory Proteins Induced by Cortisol

A
  1. Interleukin-10

2. Lipocortin (Annexin) (inhibits Phospholipase A2)

288
Q

Adrenarche

A

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
Q

Upregulate Renal 1α-hydroxylase

A
  1. High PTH
  2. Hypocalcemia (CaSR Pathway)
  3. Hypophosphatemia
290
Q

Major Site of Ketogenesis

291
Q

Digest Thyroglobulin after Endocytic Vesicles fuse with Lysosomes

A

Lysosomal Proteases

292
Q

Fate of Insulin Hormone-Receptor Complex

A

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
Q

RANK-L

A

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
Q

Mechanism for Insulin preventing release of glucose from Liver

A

Represses expression of Glucose 6-Phosphatase

295
Q

How do you know a target tissue has Spare Receptors/

A

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
Q

Downregulate Renal 1α-hydroxylase

A
  1. 1,25(OH)2D (negative feedback)
  2. Rise in [Ca]
  3. Decrease in PTH
297
Q

11β-hydroxylase

A

Catalyzes:

  1. DOC -> Corticosterone
  2. DOC -> Cortisol
298
Q

GH Excess in Childhood

299
Q

Stimulate Catecholamine Synthesis/Release

A
  1. Sympathetic Activation

2. Glucocorticoids

300
Q

Major Regulator of Ketogenesis

A

Increases with influx of Fatty Acids into Liver. Insulin has an indirect effect here in decreasing circulation of Fatty Acids

301
Q

Type of Receptor: Growth Hormone Receptor

A

Cytokine/GH/PRL/Erythropoietin Receptor Family

302
Q

Site for Conversion of 25(OH)D to 1,25(OH)2D

A

Proximal Tubules (Kidney)

303
Q

Terminus Determining PTH Biological Activity

A

N-Terminal

Intact PTH 84 AAs, Synthetic N Termin Fragment 1-34 can induce same effects

304
Q

Test designed to assess functional status of negative feedback system

A

Suppression test

305
Q

Physiological Trigger(s) of Glucagon Release

A
  1. Hypoglycemia

2. High-protein meal low in carbs (esp Arginine)

306
Q

Sex Steroids in Postnatal Growth

A

Most important is Estradiol.

  1. Responsible for puberty growth spurt
  2. Promotes linear growth
  3. Promotes maturation/fusion of Epiphyseal Growth Plate
  4. Increase growth hormone secretion
307
Q

Hormones for which Osteoblasts have Receptors

A
  1. PTH
  2. 1,25(OH)2D3
  3. Estrogens
  4. Glucocorticoids
308
Q

Protein Sparing Effect

A

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
Q

Target Cells of IGF-1

A
  1. Fibroblasts
  2. Chondrocytes
  3. Osteoblasts
  4. Adipocytes
  5. Muscles
310
Q

Incretin Receptors in β cells

A

G-protein coupled receptors stimulating glucose-dependent insulin secretion. Mechanism involves cAMP signaling

311
Q

Catalyzes Oxidation of Iodide in Follicular Lumen

A

Thyroid Peroxidase (TPO)

312
Q

Greater Affinity for IGF-1: IGFBP or IGF-1 Receptor

313
Q

9% of filtered calcium reabsorbed in…

A

Distal Convoluted Tubules

314
Q

Classical Symptoms of Diabetes

A

1) Polyuria - excessive urination
2) Polydipsia - excessive thirst
3) Polyphagia - excessive eating

315
Q

Precursor to PTH

A

Prepro-PTH

316
Q

Overview of Thyroid Hormone Effects on Cardiovascular Function

A
  1. Controls Basal Metabolic Rate
  2. Increases Cardiac Output
  3. Potentiates Catecholamines
317
Q

Pseudohypoaldosteronism

A

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
Q

Thyroxine-Binding Globulin (TBG)

A

Highest affinity. Least abundant of Thyroid hormone binding proteins but binds most.

Affinity for T4 > T3

319
Q

Osteocalcin

A

Another bone formation marker

320
Q

Intracellular Mechanism: α2-adrenergic receptor

A

Decreased cAMP

321
Q

Psuedohypoparathyroidism

A

Genetic disorder of target tissue resistance to PTH

322
Q

Cortisol Effect on Bones/Calcium Homeostasis

A

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
Q

Transports Dopamine into Secretory Granule after conversion from DOPA

A

Vesicular Monoamine Transporter (VMAT)

[Catecholamine-H+ Exchanger]

324
Q

Counterregulatory Hormones

A

Released in response to hypoglycemia (esp. Acute)

  1. Glucagon
  2. Epinephrine
  3. Growth Hormone
  4. Cortisol
325
Q

Glucose Transporter in Liver

326
Q

Endocrine Secretions in Pancreas

A
  1. Insulin (β cells)
  2. Glucagon (α cells)
  3. Somatostatin (δ cells)
  4. Pancreatic Polypeptide
327
Q

Graves Disease

A

Most common cause of Thyrotoxicosis. Autoimmune disorder characterized by Hyperplastic Goiter.

TSH levels suppressed by high circulating levels of Thyroid Hormone

328
Q

Hormone-Sensitive Lipase

A

Breaks TAGs down into Fatty Acids and Glycerol in Adipose Tissue.

  • Stimulated by: Epinephrine
  • Inhibited by: Insulin
329
Q

Cancellous / Trabecular Bone

A

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
Q

Glycoprotein Family of Hormones

A
  1. FSH
  2. LH
  3. TSH
  4. Human Chorionic Gonadotropin (hCG)
331
Q

Treatment use of Propanolol

A

β-adrenergic blocking drug useful in treating Hyperthyroid symptoms

332
Q

Glucokinase vs Hexokinase

A

Glucokinase has lower affinity (high Km). Basically, active only when lots of glucose

333
Q

GH Secretion Pattern

A
  1. Secretory Pulses

2. Circadian Pattern

334
Q

Metabolic Conditions Inhibiting GH Secretion

A
  1. Hyperglycemia

2. Elevated Free FAs

335
Q

Catecholamine Exocytosis Complex

A

Catecholamines are released in a complex with

  1. ATP
  2. Ca2+
  3. Chromogranin
  4. Other Peptides (ex: β-endorphin)
336
Q

Principal Site of Insulin Degradation

337
Q

Steroid Hormone Receptors when Bound

A

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
Q

Receptor Type: Thyroid Hormone Receptor

A

Ligand-Activated (Nuclear) Transcription Factor

339
Q

Cortisol Effect on Glycogen Metabolism

A

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
Q

Secondary Hypothyroidism and Causes

A

Result of Hypofunctional Pituitary Gland. Isolated TSH deficiency

Causes:

  1. Infiltrative disorders
  2. Surgery
  3. Trauma
341
Q

ED50

A

Concentration of hormone that produces half-maximal response; common measurement of sensitivity

342
Q

Acute Effects of ACTH Release

A
  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
Q

Vitamin D Effects in Kidney

A
  1. negative inhibition on Renal 1α-hydroxylase

2. Stimulates 24-hydroxylase

344
Q

Mexedema

A

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
Q

Counterregulatory Effects of Epinephrine

A
  1. Inhibits glucose utilization by muscles
  2. Stimulates Glycogenolysis
  3. Stimulates Gluconeogenesis
  4. Inhibits insulin secretion
  5. Stimulates glucagon secretion
  6. Stimulates lipolysis
346
Q

Glycoprotein Hormone β Subunits

A

Unique for each protein

347
Q

Required to detach Thyroglobulin from Colloid

A

Proteolysis of Thyroglobulin

348
Q

Acyl-CoA Cholesterol Acyltransferase

A

Enzyme in the ER which converts Cholesterol to Cholesterol Esters for storage in Steroidogenic cells.

349
Q

Hypophysiotropic Hormones with Gi Mechanism

A
  1. Somatostatin

2. Dopamine

350
Q

Enzyme converting Tyrosine to DOPA

A

Tyrosine Hydroxylase

351
Q

Nervous System Effects of Thyroid Hormone

A
  1. Promotes Axon/Dendrite Growth
  2. Synapse Formation
  3. Myelination

Absence leads to mental retardation. Effects learning, memory, responsiveness, wakefulness, etc.

352
Q

Contained in Insulin Secretory Granule

A

Prohormone converting enzymes

353
Q

Factors in Prenatal Growth

A
  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
Q

Aldosterone Synthase

A

Enzyme only found in the Zona Glomerulosa.

Converts DOC to Aldosterone.

355
Q

Neurohypophysis

A

Posterior Pituitary

Composed of neural tissue, formed as downward evagination of floor of embryonic brain.

Direct hormone release into circulation

356
Q

Components of Preprohormone Precursors of ADH and Oxytocin

A
  1. Signal Peptide
  2. Hormone Sequence
  3. Neurophysin Domain
  4. Glycopeptide Domain (ADH only)
357
Q

Components of Serum IGF Complex

A
  1. IGF
  2. IGFBP-3
  3. Acid-Labile Subunit (ALS)

Production of all stimulated by GH

358
Q

Nutrients Stimulating Insulin Release

A

(in circulation)

  1. Glucose
  2. Amino Acids
359
Q

Docking Site for Signaling Proteins in GH Receptor Pathway

A

Phosphotyrosine Residues on GH Receptor

360
Q

Ketosis

A

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
Q

Cellular Level Influences of Thyroid Hormone

A
  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
Q

Insulin Receptor Substrates (IRS)

A

Major targets of insulin receptor tyrosine kinase activity. Multiple residues of IRS phosphorylated.

They serve as docking sites for other intracellular signaling proteins.

363
Q

Lactotrope (Hypothalamic and Anterior Pituitary Hormones)

A

Hypothalamic Hormones:

  1. Thyrotropin-Releasing Hormone (TRH) [++, Gq]
  2. Dopamine [–, Gi]

Anterior Pituitary Hormone:
1. Prolactin (PRL)

364
Q

Thyroid Hormone Binding Proteins

A
  1. Thyroxine-Binding Globulin (TBH)
  2. Transthyretin
  3. Albumin
365
Q

Transports Iodide from Follicle Cell to Lumen

A

Pendrin (Iodide-Chloride Exchanger)

366
Q

Enzymes Require for Synthesis of Cortisol and Androgens

A
  1. 17α-hydroxylase
  2. 17,20-lyase

NOT FOUND IN ZONA GLOMERULOSA

367
Q

Stimulates Erythropoetin Synthesis

368
Q

C-Terminal Telopeptides of Type 1 Collagen (CTX)

A

Product of bone collagen degradation used as a marker of bone turnover

369
Q

Insulin Effect on Muscle Protein

A

Skeletal Muscle

  1. Stimulates AA uptake and protein synthesis
  2. Inhibits proteolysis
370
Q

Cortisol Effect on CNS

A

Mood, behavior, wakefulness, perception of stimuli affected by excess/deficiency

371
Q

DOC as a Mineralocorticoid

A

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
Q

Human Chorionic Gonadotropin (hCG)

A

Placental Glycoprotein hormone.

  • α subunit identical to FSH, LH, and TSH
  • β subunit is same as LH plus an additional 32 AAs
373
Q

Insulin Effects on Adipose Tissue

A
  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
Q

Enzyme Phosphorylating Glucose in Liver

A

Glucokinase

375
Q

Conn Syndrome and Cause

A

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
Q

STAT Proteins

A

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
Q

Goiter

A

Enlarged Thyroid gland

378
Q

Steroidogenic Acute Regulatory Protein (StAR)

A

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
Q

Cortisol Effects on Catecholamine Release

A

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
Q

Most Common Thyroid Hormone in Circulation

A

T4 (60-70x greater than T3)

381
Q

Dipeptidyl Peptidase 4 (DPP4)

A

Rapidly inactivates GIP and GLP-1

382
Q

Mechanism of Reabsorption: Proximal Tubule

A

Passive Paracellular

383
Q

Mechanism of Sympathetic Activation on Catecholamine Release

A

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
Q

Hashimoto Thyroiditis

A

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
Q

Unique Feature of Lactotropes/Prolactin Release

A

Under tonic inhibition by Dopamine

386
Q

Stimulate Transcription of StAR

A
  1. Angiotensin II via Ca/Calmodulin mechanism (Zona Glomerulosa)
  2. ACTH via cAMP mechanism (Zona Fasciculata/Reticularis)
387
Q

Hormonal Regulators of Prenatal Growth

A
  1. IGF-1/IGF-2 (independent of GH stimulation)
  2. Insulin
  3. Glucocorticoids

GH NOT major regulator

388
Q

Principle component of a Colloid

A

Thyroglobulin (TG) – a glycoprotein

389
Q

Pheochromocytomas

A

Catecholamine-producing tumors of Chromaffin Cells of Adrenal Medulla (90%) or Extra-Adrenal Ganglia

Most Common Clinical Feature: Hypertension

390
Q

Hormonal Regulators of Postnatal Growth

A
  1. Growth Hormone (most important)
  2. Thyroid Hormone
  3. Sex Steroids
  4. Insulin
  5. Glucocorticoids
391
Q

Phenylethanolamine-N-Methyltransferase (PNMT)

A

Converts Norepinephrine to Epinephrine in the cell cytoplasm after NE exists granule.

392
Q

Thyroid-Stimulating Immunoglobulin (TSI)

A

Found in the serum during Graves Disease.

TSI binds to TSH receptor and induces similar effects

393
Q

Hyperosmolar Hyperglycemia State (HHS)

A
  1. Sever hyperglycemia
  2. Hyperosmolality
  3. Dehydration
394
Q

Principal Counter-Regulatory Hormone

A

Glucagon (under normal conditions)

395
Q

Somatotrope (Hypothalamic and Anterior Pituitary Hormones)

A

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
Q

Functions of Mineralocorticoids

A
  1. Maintain Extracellular Fluid by regulating Na Reabsorption (Main)
  2. Promote K+ Excretion
  3. Promote H+ Excretion
397
Q

Tertiary Hypothyroidism

A

Rare. Diminished TRH release. Damage to Hypothalamus

398
Q

Adenohypophysis

A

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
Q

Mechanisms of Glucagon Promoted Gluconeogenesis

A
  1. Increases Activity of Gluconeogenic Enzymes (via PKA)
  2. Inhibits Glycolytic enzymes
  3. Stimulates uptake of Amino Acids (esp Alanine)
400
Q

Receptor Type: Steroid Hormone

A

Ligand-Activated Transcription Factors

401
Q

Overview of Vitamin D Actions

A
  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
Q

Parasympathetic Nervous System Effect on Insulin Release

A

Vagal stimulation in presence of glucose promotes insulin release

403
Q

Intracellular Mediator of Calcitonin Actions

404
Q

Proteins involved in Transcellular Reabsorption of Ca2+ (Ascending Limb of Loop)

A
  1. TRPV5 Important One
  2. Calbindin-D28k
  3. PMCA
  4. NCX
405
Q

Principle Organic Molecule in Bone

A

Type 1 Collagen

406
Q

GH and IGF-1 Levels: Starvation/Protein-Calorie Malnutrition

A
  1. GH elevated

2. IGF-1 decreased (insulin necessary for max IGF-1 production by liver)

SF4 (5 decks)

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