Instructions: Select the single best answer. Explanations appear immediately after each response. Your scores populate the Score Report tab in real time.
Question 1 of 5 — LO 1 · Paracrine vs Endocrine Signaling
A 58-year-old man undergoes endoscopic biopsy of the gastric antrum. Histology shows intermingled G cells that release a hormone into local capillaries reaching parietal cells, δ (D) cells whose product diffuses across short distances to inhibit neighboring G cells WITHOUT entering the general circulation, and enterochromaffin-like (ECL) cells that release histamine acting on parietal cells only inches away. Which term best describes the action of the δ-cell product on G cells in this tissue?
Which of the following best describes this signaling mode?
AEndocrine
BParacrine
CAutocrine
DNeurocrine
EJuxtacrine (contact-dependent)
B — Paracrine. The defining feature is local diffusion to adjacent cells WITHOUT entering the bloodstream. Somatostatin from δ cells inhibits neighboring G cells in this exact paracrine fashion. Endocrine (A) requires blood-borne travel to distant target — true for gastrin from G cells to parietal cells via local capillaries. Autocrine (C) would act on δ cells themselves. Neurocrine (D) requires a neuron (e.g., ADH). Juxtacrine (E) needs direct cell-cell contact via surface molecules.
Question 2 of 5 — LO 2 · Hormone Classification (incl. eicosanoids)
A researcher studies five molecules that carry intercellular signals. Hormone W is stored in vesicles, circulates free, has a half-life of 4 minutes, and binds a 7-pass transmembrane receptor on hepatocytes. Hormone X is synthesized on demand from cholesterol, circulates bound to a specific carrier, has a half-life of ~7 days when stored in colloid, and binds a nuclear receptor pre-bound to DNA. Hormone Y is derived from tyrosine, stored in granules, released by exocytosis, and binds both α- and β-adrenergic GPCRs. Hormone Z is derived from cholesterol, NOT stored, and binds a cytoplasmic receptor complexed with HSP90. Hormone V is released locally by most cell types, is derived from a 20-carbon fatty acid liberated from membrane phospholipids by phospholipase A2, acts on neighboring cells through EP/TP/LT family GPCRs, and is synthesized in seconds upon stimulation.
Which of the following identifications is most consistent with all five descriptions?
AW = cortisol, X = T4, Y = epinephrine, Z = glucagon, V = insulin
BW = glucagon, X = T4, Y = epinephrine, Z = cortisol, V = prostaglandin E₂
CW = epinephrine, X = cortisol, Y = T4, Z = insulin, V = aldosterone
DW = insulin, X = estradiol, Y = dopamine, Z = aldosterone, V = leukotriene D4
EW = oxytocin, X = vitamin D, Y = melatonin, Z = testosterone, V = thromboxane A2
B. Work each property: W (vesicle-stored, free, 4-min ½-life, GPCR) = a peptide using a GPCR — fits glucagon (insulin uses an RTK, not a GPCR, so D is wrong). X (colloid, TBG-bound, 7-day ½-life, nuclear receptor pre-bound to DNA) = T4. Y (tyrosine-derived, granule-stored, α/β GPCR) = epinephrine. Z (cholesterol-derived, NOT stored, cytoplasmic receptor/HSP90) = cortisol. V (arachidonic-acid-derived, local, EP/TP/LT GPCRs, synthesized on demand) = an eicosanoid (PGE₂). Key concept: solubility + precursor + storage + receptor location jointly classify every hormone class — including the lipid-derived eicosanoids, which act LOCALLY at membrane GPCRs rather than systemically at nuclear receptors like steroids.
Question 3 of 5 — LO 2 · Glycoprotein Hormones
A 24-year-old woman at 12 weeks of her first pregnancy presents with severe vomiting, tachycardia (118 bpm), and a fine resting tremor. She has lost 4 kg. Physical exam reveals no goiter and no eye signs. Laboratory studies: TSH <0.01 mIU/L (low), free T4 3.8 ng/dL (high), β-hCG 580,000 mIU/mL, and anti-TSH-receptor antibodies are negative. Pelvic ultrasound reveals a "snowstorm" pattern with no fetal heart tones. Which feature of glycoprotein hormone structure best explains her thyroid findings?
AhCG and TSH share an identical β-subunit
BhCG and TSH share an identical α-subunit with structurally similar β-subunits
ChCG has intrinsic protease activity that activates TSH receptors
DhCG directly competes with T3 at nuclear receptors
EhCG stimulates thyroid peroxidase via iodide uptake
B. The four glycoprotein hormones — TSH, LH, FSH, hCG — share an IDENTICAL α-subunit, with specificity from a unique β-subunit. However, hCG-β and TSH-β are structurally similar. At extremely high hCG (>100,000 mIU/mL, seen in molar pregnancy / hyperemesis gravidarum / choriocarcinoma), hCG weakly cross-activates the TSH receptor → transient hyperthyroidism. This resolves after molar evacuation. Choice A reverses the subunit pattern. Choice B correctly identifies the structural basis for cross-reactivity.
Question 4 of 5 — LO 6 · GPCR Signal Transduction
A 62-year-old man on chronic lithium for bipolar disorder develops polyuria (8 L/day), polydipsia, and serum Na⁺ 151 mEq/L. Urine osmolality is 125 mOsm/kg. After water deprivation it rises only to 180. Intranasal desmopressin (DDAVP) administration fails to raise urine osmolality above 210 mOsm/kg. A renal biopsy demonstrates downregulation of aquaporin-2 in collecting duct principal cells. Failure of which of the following signaling steps best explains his concentrating defect?
AADH release from the posterior pituitary
BBinding of ADH to V1 receptors on vascular smooth muscle
CV2-receptor Gs coupling → adenylyl cyclase → cAMP → PKA → aquaporin-2 insertion
DActivation of Gq → PLC → IP3/DAG pathway in principal cells
ENuclear translocation of the vitamin D receptor in the collecting duct
C — V2 receptor Gs / cAMP pathway. This is lithium-induced nephrogenic DI. The V2 receptor for ADH is Gs-coupled → cAMP → PKA → phosphorylation and trafficking of aquaporin-2 water channels to the apical membrane. Lithium disrupts this pathway intracellularly, so even exogenous desmopressin (ADH mimetic) cannot concentrate urine. A fails the desmopressin test (central DI responds). B is for V1 (vasoconstriction, NOT water). D is Gq — V1 uses Gq but V2 uses Gs. E is irrelevant. Tests LO 6 directly at the clinical level.
Question 5 of 5 — LO 6 · RTK vs GPCR Signaling
A 45-year-old man with obesity (BMI 34) has fasting glucose 178 mg/dL and HbA1c 8.9%. A research assay reveals that his hepatocyte insulin receptors bind insulin normally but fail to autophosphorylate on tyrosine residues in response to insulin exposure. Consequently, IRS-1 is NOT phosphorylated, PI3K signaling is abolished, and GLUT4 translocation to the cell membrane does not occur. A defect in which broad category of receptor best explains his insulin resistance?
AG-protein coupled receptor (seven-transmembrane)
BReceptor tyrosine kinase
CCytokine receptor signaling through JAK-STAT
DLigand-gated ion channel
ECytoplasmic nuclear receptor bound to HSP90
B — Receptor tyrosine kinase. The insulin receptor is the prototypic RTK: insulin-induced dimerization → trans-autophosphorylation on tyrosine → recruitment of IRS-1 → PI3K/Akt (metabolic) + MAPK (growth) arms. Failure at autophosphorylation halts all downstream signaling — even though insulin BINDS normally. This is the canonical exam contrast with glucagon (choice A, a GPCR). Other RTKs: IGF-1, EGF, FGF, PDGF, VEGF, FGF23. GH and prolactin (C) use JAK-STAT. Steroids use E.
Instructions: Select the single best answer. Questions emphasize biosynthesis rate-limiting steps, enzyme blockade pharmacology, and storage vs. synthesis control of hormone release.
Question 1 of 5 — LO 3 · Catecholamine Rate-Limiting Enzyme
A 40-year-old woman with episodic hypertensive crises (peak BP 230/130), diaphoresis, headache, and palpitations has a 4-cm right adrenal mass. Plasma free metanephrines are markedly elevated. Her anesthesia team plans surgery in 3 weeks and wants to control catecholamine synthesis preoperatively. They administer metyrosine (α-methyltyrosine), which inhibits the rate-limiting enzyme of catecholamine biosynthesis. Which enzyme is blocked?
ATyrosine hydroxylase (Tyr → L-DOPA)
BDOPA decarboxylase (L-DOPA → dopamine)
CDopamine β-hydroxylase (DA → NE)
DPNMT (NE → Epi)
EMonoamine oxidase (MAO)
A — Tyrosine hydroxylase. TH converts tyrosine to L-DOPA using BH4 (tetrahydrobiopterin) as a cofactor and is the RATE-LIMITING step in catecholamine synthesis. Metyrosine is a competitive substrate analog that blocks TH → decreases NE/Epi synthesis by up to 80% → safer surgery in pheochromocytoma. DOPA decarboxylase (B) is blocked peripherally by carbidopa (Parkinson's). PNMT (D) is only in adrenal medulla (cortisol-induced) and converts NE → Epi — blocking it wouldn't reduce catecholamine load meaningfully. MAO (E) degrades catecholamines; inhibiting it would RAISE them.
Question 2 of 5 — LO 3 · L-DOPA / Carbidopa Pharmacology
A 66-year-old man with Parkinson disease is started on L-DOPA. Within a week he develops severe nausea, orthostatic hypotension, and minimal improvement in motor symptoms. His neurologist adds carbidopa to the regimen. Motor symptoms improve significantly, nausea resolves, and orthostasis improves. Carbidopa produces these benefits by which mechanism?
AIt is a direct dopamine D2 agonist in the CNS
BIt inhibits peripheral DOPA decarboxylase without crossing the blood-brain barrier
CIt inhibits central MAO-B to prolong dopamine activity
DIt antagonizes striatal α₂-adrenergic receptors
EIt is converted to dopamine in the CNS faster than L-DOPA is
B. The rate-limiting enzyme for catecholamines (TH) is upstream of L-DOPA; once L-DOPA is given, DOPA decarboxylase in peripheral tissues converts it to dopamine BEFORE it can cross the BBB. Peripheral dopamine causes nausea (area postrema is outside BBB) and orthostasis, while only L-DOPA that reaches the CNS helps Parkinson symptoms. Carbidopa is a DOPA decarboxylase inhibitor that CANNOT cross the BBB — it blocks peripheral conversion, allowing more intact L-DOPA to reach the brain and be decarboxylated there. This tests the clinically critical fact that L-DOPA crosses the BBB but dopamine does NOT.
Question 3 of 5 — LO 4 · 21-Hydroxylase Deficiency (CAH)
A 16-day-old 46,XX neonate presents with lethargy, poor feeding, vomiting, and dehydration. Genital exam shows clitoromegaly and partial labial fusion. Labs: Na⁺ 124 mEq/L, K⁺ 6.8 mEq/L, HCO₃⁻ 17 mEq/L, glucose 45 mg/dL, serum 17-hydroxyprogesterone 4,500 ng/dL (markedly elevated). Adrenal ultrasound shows bilateral hyperplasia. Which enzyme defect most likely explains her presentation?
A21-hydroxylase — ↓ cortisol + ↓ aldosterone + ↑ androgens
B11β-hydroxylase — ↓ cortisol + ↑ DOC + ↑ androgens
C17α-hydroxylase — ↑ mineralocorticoids + ↓ androgens
DAromatase — inability to convert androgens to estrogens
EDesmolase — complete failure of all steroidogenesis
A — 21-hydroxylase deficiency, the commonest form of CAH (~90%). The salt-wasting crisis (hyponatremia, hyperkalemia, hypotension) in the first 2 weeks of life + virilization of a 46,XX infant + elevated 17-OH-progesterone are pathognomonic. Blocked 21-hydroxylase can't make cortisol OR aldosterone, and precursors are shunted into the androgen pathway → virilization. 11β (B) = HTN + virilization (no salt-wasting). 17α (C) = HTN + NO virilization (low androgens). Desmolase (E) would abolish all steroids — incompatible with life beyond days. Directly tests LO 4 (initial step / biosynthesis).
Question 4 of 5 — LO 4 · ACTH and StAR/Desmolase
A researcher studying adrenocortical function finds that ACTH binding to the MC2 receptor on zona fasciculata cells triggers a rapid increase in cortisol output that begins within 3 minutes of stimulation. Further investigation reveals that ACTH causes phosphorylation of a specific protein in the outer mitochondrial membrane, which then transfers cholesterol to the inner mitochondrial membrane where the FIRST committed enzymatic step of steroid biosynthesis takes place. Which protein and which enzymatic step does this pathway represent?
AStAR protein; 11β-hydroxylase (11-deoxycortisol → cortisol)
BStAR protein; desmolase / CYP11A1 (cholesterol → pregnenolone)
CSREBP; HMG-CoA reductase (HMG-CoA → mevalonate)
DACAT; aromatase (testosterone → estradiol)
EStAR protein; 3β-hydroxysteroid dehydrogenase (pregnenolone → progesterone)
B. The RATE-LIMITING step of steroid biosynthesis is cholesterol → pregnenolone, catalyzed by desmolase (CYP11A1 / P450scc) on the inner mitochondrial membrane. Because cholesterol is stored in cytoplasmic lipid droplets, access to mitochondrial desmolase is limited by the transfer step. StAR (Steroidogenic Acute Regulatory protein) shuttles cholesterol from the outer to inner mitochondrial membrane — this is the TRUE rate-limiting point. ACTH → cAMP → PKA → phosphorylates StAR → acute cortisol burst (minutes). Tests LO 4 precisely.
Question 5 of 5 — LO 3/7 · Storage vs. Synthesis Control
A 28-year-old subject is enrolled in a physiology experiment. At 8:00 AM he receives an IV dose of cosyntropin (synthetic ACTH). Serum cortisol begins to rise within 3 minutes and peaks at 30 minutes. At 10:00 AM he receives an IV dose of glucose to stimulate insulin release. Serum insulin rises within SECONDS and peaks at 5 minutes. At 12:00 PM he receives an IV dose of insulin to induce hypoglycemia and stimulate the adrenal medulla; serum epinephrine rises within seconds. Which of the following best explains why the cortisol response is so much slower than the insulin and epinephrine responses?
ACortisol is stored in vesicles while insulin is synthesized on demand
BCortisol must be synthesized de novo because steroids cannot be stored, while insulin and epinephrine are preformed and stored in vesicles/granules
CCortisol uses a slow nuclear receptor while insulin and epinephrine use fast membrane receptors
DCortisol is heavily carrier-bound so the bioavailable fraction is delayed
ECortisol circulates as a prohormone that requires activation by 11β-HSD
B. LO 7 directly: hormones released from STORES (peptides in vesicles, catecholamines in chromaffin granules, thyroid hormone in colloid) respond within seconds-to-minutes because they are preformed — only exocytosis is needed. Steroid hormones cannot be stored (lipid-soluble → can't be concentrated in a membrane-bound vesicle). They must be synthesized DE NOVO from cholesterol via StAR → desmolase → downstream enzymes, a process taking minutes to peak. This is the fundamental difference between the PROCESS of release (synthesis vs storage) tested by the lecture's LO 7. Choice C conflates receptor speed with release speed (also a real phenomenon, but not what's asked). D is true but doesn't explain the 30-minute timing.
Instructions: Select the single best answer. These questions integrate carrier-protein physiology, receptor cross-talk, and classic regulation syndromes.
Question 1 of 5 — LO 5 · Free Hormone Hypothesis
A 29-year-old woman at 20 weeks' gestation is referred for abnormal thyroid tests discovered on routine screening. She feels well. Exam: pulse 84, reflexes 2+, no tremor, no goiter, no eye signs. Labs: total T4 16.2 μg/dL (high), free T4 1.1 ng/dL (normal), TSH 1.8 mIU/L (normal), thyroid peroxidase Ab negative. Which of the following is the best explanation for the discrepancy between total and free T4?
ASubclinical Graves disease with insufficient TSH suppression
BHeterophile antibody interference with the total T4 assay
CEstrogen-stimulated hepatic production of thyroxine-binding globulin (TBG)
DPeripheral conversion of T4 to reverse T3 is accelerated in pregnancy
EPregnancy-induced downregulation of deiodinase enzymes
C. Classic free hormone hypothesis (LO 5). Pregnancy → ↑estrogen → ↑hepatic TBG synthesis → more T4 binds carrier → total T4 rises. Free T4 (the only biologically active fraction) is UNCHANGED, so the patient is clinically euthyroid with a normal TSH. Same principle applies to OCP users. Always measure FREE T4 + TSH to judge thyroid status when TBG may be altered. Graves (A) would show LOW TSH + high free T4. This same mechanism also ↑CBG → ↑total cortisol in pregnancy with normal free cortisol.
Question 2 of 5 — LO 6 · Pseudohypoparathyroidism Type 1a
A 19-year-old woman with short stature (4'11"), round face, obesity, and shortened 4th and 5th metacarpals bilaterally presents with perioral tingling and carpopedal spasm. Labs: Ca²⁺ 6.4 mg/dL, Pi 6.9 mg/dL, PTH 285 pg/mL (very high), 25-OH vitamin D normal, Mg normal. An infusion of synthetic PTH produces no increase in urinary cAMP and no phosphaturia. Genetic testing reveals an inactivating mutation in GNAS, inherited from her mother. Which statement best characterizes her disorder?
AAutoimmune destruction of parathyroid glands
BInactivating mutation of the PTH-receptor gene
CEnd-organ resistance to PTH due to inactivating Gsα mutation with maternal imprinting
DConstitutively active CaSR causing hypocalcemia
EVitamin D receptor mutation causing hereditary rickets
C — Pseudohypoparathyroidism type 1a (Albright hereditary osteodystrophy). PTH receptor is Gs-coupled → adenylyl cyclase → cAMP. Inactivating GNAS (Gsα) eliminates PTH-mediated signaling → end-organ resistance → ↑PTH tries to compensate but kidney / bone can't respond → ↓Ca²⁺, ↑Pi. Ellsworth-Howard test (PTH infusion): failure to increase urinary cAMP is diagnostic. AHO phenotype: short stature, round face, short 4th/5th metacarpals, obesity. Maternally imprinted: phenotype only if inherited from MOTHER. Tests LO 6 at the receptor-signaling-defect level.
Question 3 of 5 — LO 6 · McCune-Albright (Gsα Gain-of-Function)
A 6-year-old girl presents with precocious puberty (Tanner III breast development, vaginal bleeding). She has a single large, irregular, "coast of Maine"–bordered café-au-lait macule across her left flank. X-rays reveal multiple lytic bone lesions in the femur, pelvis, and ribs (polyostotic fibrous dysplasia). Labs: LH and FSH are low (gonadotropin-independent), but estradiol is elevated. A biopsy of one bone lesion reveals a somatic activating GNAS mutation present only in affected tissues. Which molecular mechanism best explains all of her findings?
AGermline loss-of-function Gsα mutation
BPost-zygotic activating Gsα mutation causing mosaic constitutive cAMP signaling in affected tissues
CGermline activating mutation of the LH receptor
DPTH-related peptide production by a neuroblastoma
ELoss-of-function mutation of the androgen receptor
B — McCune-Albright syndrome. Triad: (1) polyostotic fibrous dysplasia, (2) café-au-lait with "coast of Maine" borders, (3) endocrine hyperfunction (most commonly peripheral precocious puberty). Mechanism: somatic post-zygotic activating mutation in GNAS (Gsα) → constitutive adenylyl cyclase activity in mutation-carrying tissues → tonic cAMP drives hormone-independent stimulation. Must be mosaic — a germline GNAS-activating mutation would be embryologically lethal (pan-tissue constitutive cAMP). Mirror image of PHP1a: same gene, opposite mutation, opposite pathology. Tests LO 6 at the GPCR gain-of-function level.
Question 4 of 5 — LO 7 · Dose-Response Curve in T2DM
A 50-year-old woman with BMI 37 and acanthosis nigricans has fasting glucose 162 mg/dL, HbA1c 8.3%, fasting insulin 52 μIU/mL (very high), and C-peptide 5.8 ng/mL (high). A hyperinsulinemic-euglycemic clamp reveals that her glucose disposal rate reaches half-maximal response at an insulin concentration 4× higher than in a BMI-matched non-diabetic control; her maximum glucose disposal is also reduced by ~30%. Over 6 years she transitions from oral agents to basal insulin to a full insulin regimen; her fasting insulin and C-peptide decline progressively. Which statement best describes the change in her insulin dose-response curve?
ALeftward shift (↓ EC50) with preserved maximum — increased sensitivity
BRightward shift (↑ EC50) with reduced maximum — decreased sensitivity due to receptor down-regulation + post-receptor signaling defects
CNo shift in EC50 but decreased insulin secretion only
DLeftward shift in EC50 but lower maximum — denervation hypersensitivity pattern
ECurve becomes biphasic due to receptor isoform switching
B — Rightward shift with reduced maximum. This is the canonical LO 7 result: insulin resistance means a higher EC50 (more hormone for half-max) AND a lower plateau when post-receptor signaling is damaged. Overnutrition → chronic hyperinsulinemia → receptor INTERNALIZATION / DOWN-REGULATION + IRS-1 serine phosphorylation + SOCS proteins → shifted curve. Early T2DM compensates with HIGH insulin + HIGH C-peptide (climb-the-shifted-curve strategy); β-cell exhaustion eventually reduces endogenous insulin. Metformin / GLP-1 agonists / weight loss shift the curve LEFT. "Little hormone → Lots of receptors; Lots of hormone → Lose receptors" — the LO 7 shorthand.
Question 5 of 5 — LO 2/7 · C-Peptide & Factitious Hypoglycemia
A 38-year-old hospital pharmacy technician with no known diabetes presents to the ED after a witnessed seizure. Fingerstick glucose during the event was 32 mg/dL. Laboratory data obtained during the hypoglycemic episode: serum insulin 140 μIU/mL (very high), C-peptide 0.15 ng/mL (LOW), proinsulin undetectable, serum sulfonylurea screen negative, IGF-2 normal. She is hemodynamically stable and responds to IV dextrose. Pancreatic MRI shows no lesions. Which of the following is the most likely diagnosis?
AInsulinoma
BSulfonylurea abuse
CSurreptitious exogenous insulin administration
DNon-islet-cell tumor hypoglycemia (IGF-2 mediated)
EAdrenal insufficiency
C — Exogenous insulin administration (factitious hypoglycemia). Peptide hormone biology from LO 2/7 in action. Endogenous insulin originates from proinsulin, which is cleaved in Golgi into equimolar amounts of insulin + C-peptide. Therefore endogenous excess (insulinoma, sulfonylurea stimulation) produces HIGH insulin + HIGH C-peptide. Injected commercial insulin has NO C-peptide, so ↑insulin + ↓↓C-peptide = exogenous. Sulfonylureas (B) stimulate endogenous release (both high); a negative urine drug screen rules it out here. Insulinoma (A) would show high insulin AND high C-peptide. This high-yield clinical application is a direct consequence of the synthetic pathway taught in the lecture.
Source review. Every item below was pulled from your 3rd Party Biochem + Physio folders and hand-mapped to END01 Intro-to-Hormones LOs (hormone classification, catecholamine/steroid biosynthesis, carrier proteins & half-life, receptor location & signaling, cellular sensitivity). Questions are grouped by LO to complement — not duplicate — the in-house exam Blocks 1-3 above.
Legend:
BRS Biochem
BRS Physio
Waite & Sheakley
Group A · Hormone Classification & Biosynthesis (LOs 2, 3, 4)
Ext Q1 — LO 2 · Chemical Classes — Waite & Sheakley Q6
A 68-year-old woman with type 2 diabetes mellitus and hypothyroidism, who occasionally uses a hydrocortisone topical cream, asks about the potential to administer thyroxine and insulin through the skin. The physician's answer includes information about the chemical versatility of hormones. To which chemical classes of hormones do cortisol, thyroxine (T4), and insulin belong, respectively?
ASteroid hormones · Amino acid derivatives · Peptide hormones
BProtein hormones · Amino acid derivatives · Steroid hormones
CCatecholamines · Amino acid derivatives · Peptide hormones
DSteroid hormones · Peptide hormones · Catecholamines
EProtein hormones · Peptide hormones · Catecholamines
A. Cortisol is a steroid (cholesterol-derived, names end in "-ol"/"-one"; also aldosterone, testosterone, progesterone, estradiol). Thyroxine (T4) is an amino-acid-derived hormone (from tyrosine; other tyrosine-derived hormones are epinephrine, norepinephrine, dopamine). Insulin is a peptide. This maps directly onto LO 2: hormones are classified by structure, solubility, and storability — steroids are lipid-soluble and not stored, amino acid derivatives split into water-soluble catecholamines vs. lipid-soluble thyroxine, and peptides are water-soluble and vesicle-stored. Transcutaneous delivery of lipid-insoluble hormones (insulin, T4 when salt-form) is hard because they need lipid-soluble carriers.
Ext Q2 — LO 3 · Tyrosine as Hormone Precursor — Waite & Sheakley Q1
Clinical studies that examine the effectiveness of L-tyrosine as a dietary supplement to increase cognitive performance have thus far shown inconclusive results. Nevertheless, advertisements for L-tyrosine supplements are common. Physicians should discourage patients with which of the following conditions from taking tyrosine supplements without supervision?
AAddison's disease
BCongenital adrenal hyperplasia (21-hydroxylase form)
CGraves' disease
DHashimoto's disease
EType 1 diabetes
C — Graves' disease. Tyrosine is the precursor for epinephrine, dopamine, norepinephrine, AND thyroxine. In hyperthyroid Graves' patients, extra tyrosine substrate can push T4 synthesis further into the danger zone. Addison's (A) and 21-OH CAH (B) have LOW cortisol; tyrosine may actually help stress tolerance. Hashimoto's (D) is hypothyroid — the substrate-loading is not contraindicated. Diabetes (E) is not on the tyrosine axis. LO 3 note: the same tyrosine → L-DOPA → dopamine → NE → Epi pathway that makes catecholamines ALSO feeds thyroid hormone synthesis via iodination of tyrosine residues on thyroglobulin.
Ext Q3 — LO 2/3 · Hormone from Tyrosine — BRS Biochem Q14
A 20-year-old male presents with weight loss, heat intolerance, bilateral exophthalmos, lid lag, sweating, and tachycardia. These symptoms are due to an increased production and secretion of a hormone. From which of the following is this hormone derived?
ACholesterol
BDopamine
CTryptophan
DTyrosine
EGlutamate
D — Tyrosine. The patient has Graves hyperthyroidism. Thyroid hormone is derived from tyrosine (iodinated at two sites on tyrosyl residues of thyroglobulin → MIT + DIT → T3/T4). Catecholamines (dopamine, NE, Epi) are ALSO derived from tyrosine but via a separate enzymatic pathway (TH → DDC → DBH → PNMT). Cholesterol (A) gives rise to steroid hormones. Tryptophan (C) gives rise to serotonin and melatonin. Glutamate (E) gives rise to GABA via decarboxylation. LO 3 directly.
Ext Q4 — LO 4 · Steroid Biosynthesis Precursor — BRS Biochem Q11
A 35-year-old female presents with central obesity, a "buffalo hump," Type 2 diabetes, abdominal striae, and "moon facies." The hormone being overproduced in this syndrome is produced from which one of the following compounds?
AProgesterone
BTestosterone
CEstradiol
DAldosterone
EChenocholic acid
A — Progesterone. The patient has Cushing syndrome → overproducing cortisol. In the steroid biosynthesis pathway, cholesterol → pregnenolone (via desmolase / StAR — the rate-limiting step, LO 4) → progesterone → 17-OH progesterone → 11-deoxycortisol → cortisol. Progesterone is also an intermediate upstream of aldosterone and testosterone. Testosterone (B) is a precursor for estradiol (via aromatase), not cortisol. Chenocholic acid (E) is a bile salt derived directly from cholesterol, not through progesterone. LO 4 directly.
Group B · Carrier Proteins & Hormone Half-Life (LO 5)
Ext Q5 — LO 5 · Half-Life & Carrier Proteins — Waite & Sheakley Q4
In a research study with healthy people, the half-lives of four hormones in serum were measured and the following average results were recorded:
Hormone 1: 1–3 minutes
Hormone 2: 4–6 minutes
Hormone 3: 8–24 hours
Hormone 4: 7 days
Which of the following are the four measured hormones (1 → 4)?
AAngiotensin II · Insulin · Total T3 · Total T4
BTotal T4 · Angiotensin II · Insulin · Total T3
CTotal T4 · Total T3 · Angiotensin II · Insulin
DInsulin · Total T3 · Total T4 · Angiotensin II
EAngiotensin II · Total T3 · Insulin · Total T4
A. Peptide hormones are water-soluble, circulate free, and have SHORT half-lives roughly proportional to size. Angiotensin II (8 aa) < insulin (51 aa). Lipid-soluble hormones (T3, T4, steroids) bind carriers (TBG, albumin, CBG, SHBG) → LONG half-life proportional to carrier affinity. T4 binds TBG tightly → ~7-day half-life. T3 is loosely bound → hours. Net LO 5: carriers extend half-life, and only the FREE fraction is biologically active. The rank order 1→4 is angiotensin II → insulin → T3 → T4.
Group C · Receptor Classification & Signaling (LO 6)
Ext Q6 — LO 6 · Nuclear Receptor Binding — BRS Physio Ch 27 Q1
Which of the following hormones initiates its actions at target tissues by binding to nuclear receptors?
AAdrenocorticotropic hormone (ACTH)
BVasopressin
CEpinephrine
DInsulin-like growth factor-1
EThyroid hormone
E — Thyroid hormone. Per LO 6: receptor classification is by subcellular location. Thyroid hormone, steroid hormones, and vitamin D are lipophilic → diffuse across the plasma membrane → bind nuclear receptors (some pre-bound to DNA, some cytoplasmic/HSP90-bound) → act as transcription factors. ACTH (A, peptide) and vasopressin (B, peptide) bind membrane GPCRs. Epinephrine (C) binds α/β-adrenergic GPCRs. IGF-1 (D) binds a membrane receptor tyrosine kinase. This is the canonical "lipid-soluble → nuclear / water-soluble → membrane" split.
Ext Q7 — LO 6 · Shared Receptor Strategy — BRS Biochem Q12
Patients with both Graves disease and Cushing syndrome are overproducing hormones that have which one of the following in common?
AReacting with receptors in the cell membrane
BUtilizing second messengers (cAMP / IP3)
CBinding to intracellular receptors
DBinding RNA to produce physiologically active proteins
EInducing rRNA to ablate target-gene expression
C — Intracellular receptors. Graves = excess thyroid hormone; Cushing = excess cortisol. Both are lipophilic → cross the plasma membrane → bind intracellular (cytoplasmic/nuclear) receptors → the hormone-receptor complex binds DNA hormone response elements to regulate transcription. Peptide hormones and catecholamines are the ones that use membrane receptors + second messengers (A, B). The HRE binds DNA, not RNA (D). rRNA does not ablate gene expression — microRNAs do (E). LO 6 at the clinical-overlap level.
Ext Q8 — LO 4/6 · Steroid Hormone Properties Table — BRS Biochem Q31
A 69-year-old man has been feeling lethargic, and at his yearly physical exam had his testosterone levels determined. The blood work came back with a value of 168 ng/dL (normal 250-800). He agrees to biweekly testosterone injections. Which row best represents the properties of testosterone in this patient?
Precursor to Receptor Estradiol is Represses GC Stimulates
active androgen? location precursor? synthesis? GnRH release?
A. No Cytoplasm Yes Yes No
B. No Nucleus No Yes Yes
C. Yes Nucleus No No Yes
D. Yes Cytoplasm Yes No Yes
E. Yes Nucleus No No No
ARow A
BRow B
CRow C
DRow D
ERow E
E. Testosterone is reduced to DHT (dihydrotestosterone), the more active androgen (→ "Yes"). As a steroid, it binds an intracellular/nuclear receptor (→ "Nucleus"); the hormone-receptor complex acts as a transcription factor. Testosterone is a PRECURSOR of estradiol (via aromatase) — NOT the other way around (→ "No"). It does not repress glucocorticoid synthesis (→ "No"). Negative feedback: testosterone INHIBITS GnRH release, so "Stimulates GnRH" is "No". LO 4 (steroid precursor relationships) + LO 6 (intracellular receptor location) jointly.
Ext Q9 — LO 6 · Thyroid Hormone Mechanism — Waite & Sheakley Q33
A patient with hypothyroidism is prescribed a synthetic thyroxine analogue, 50 µg orally each day. He reads about the multiple functions of this drug and wants to understand the mechanism of action. To which of the following does the drug bind, in order to activate its cellular mechanism of action?
ANuclear thyroid hormone receptors in order to regulate DNA transcription
BIodine in order to be transported across cell membranes
CPlasma membrane receptors in order to activate secondary messengers
DRetinoid X nuclear receptors in order to bind iodine
ERNA polymerase in order to bind to nuclear receptors
A. Thyroid hormones bind nuclear thyroid hormone receptors. The hormone-receptor complex binds thyroid hormone response elements (TREs) on DNA of target cells → regulates transcription. The TH receptor often heterodimerizes with RXR (D is close but the purpose of RXR is NOT "to bind iodine" — iodine is already on the hormone). Thyroid hormones do not use plasma-membrane receptors or 2nd messengers (C). RNA polymerase (E) is recruited BY the hormone-receptor-HRE complex, not the target of the hormone. LO 6: receptor location drives mechanism.
Ext Q10 — LO 6 · RTK Signaling & Cross-Reactivity — Waite & Sheakley Q3
A new long-acting insulin analogue is tested for potential carcinogenicity. As part of drug development, tests for abnormal cell growth must always be included, since an insulin analogue carries the risk of enhancing signaling of which of the following hormones?
AGlucagon
BInsulin-like growth factor 1 (IGF-1)
CThyroid hormone
DThyroid-stimulating hormone
EThyrotropin-releasing hormone
B — IGF-1. Insulin and IGF-1 both bind receptor tyrosine kinases (RTKs) and their receptors share ~50% sequence identity with overlapping ligand specificity at high concentrations. A pharmacologic insulin analog may unintentionally over-activate IGF-1 mitogenic pathways (MAPK/ERK arm) → cell-proliferation / carcinogenicity risk. Glucagon (A) uses a GPCR (Gs → cAMP). Thyroid hormone (C) uses a NUCLEAR receptor regulating transcription. TSH (D) uses GPCR → cAMP; TRH (E) uses GPCR → IP3/DAG — none of those intersect with RTK signaling. Tests LO 6 receptor-class distinctions used clinically in drug design.
Group D · Cellular Sensitivity & Response (LO 7)
Ext Q11 — LO 5/7 · What Regulates Hormone Action — BRS Physio Ch 27 Q2
Hormonal actions are regulated by:
AAffinity of receptors for the hormone
BThe number of receptors for the hormone
CThe degree of binding of hormone to plasma proteins
DThe concentration of hormone in the blood
EAll of the above
E — All of the above. This is the composite of LOs 5 and 7 in one stem. Cellular response is governed by: (1) receptor affinity, (2) receptor number (up/down-regulation = sensitivity regulation), (3) fraction of free hormone (carrier-bound vs free — only free is bioactive), and (4) total circulating concentration. Any single factor can shift the dose-response curve; together they determine EC50 and maximum response. The LO 7 shorthand: "Little hormone → lots of receptors; lots of hormone → lose receptors."
Ext Q12 — LO 7 · Responsiveness vs Sensitivity — Waite & Sheakley Q5
An in vitro insulin dose-response curve was created from a patient with multiple endocrine neoplasia. Glucose in the form of [14C-U] 2-deoxyglucose was added to freshly isolated adipocytes, and glucose transport was quantified at increasing insulin concentrations. The patient's curve is shifted to the right compared to controls, but maximum glucose uptake is still reached at very high insulin levels. Which best describes the patient's insulin responsiveness and insulin sensitivity?
AResponsiveness ↓ · Sensitivity unchanged
BResponsiveness ↓ · Sensitivity ↑
CResponsiveness ↓ · Sensitivity ↓
DResponsiveness unchanged · Sensitivity ↓
EResponsiveness unchanged · Sensitivity ↑
D — Responsiveness unchanged; Sensitivity decreased. Key LO 7 vocabulary: Responsiveness = maximal effect (plateau of the curve). Sensitivity = EC50 (concentration producing half-maximal effect). A rightward shift with preserved maximum = normal responsiveness but decreased sensitivity (↑ EC50). This typically reflects decreased receptor AFFINITY, fewer receptors at given dose, excess hormone degradation, or a competitive antagonist. If responsiveness were decreased, the curve would be FLATTENED (lower plateau) — which instead points to post-receptor signaling defects or a loss of target cells. Compare with the T2DM vignette in Block 3 Q4, which combines BOTH patterns.