Endocrine System: Hormones and Their Sources

The endocrine system is the body's slow-but-precise chemical messaging network. Where the nervous system fires in milliseconds and targets individual cells, the endocrine system signals through the bloodstream — reaching every tissue but acting over seconds to hours. The MCAT tests why the body needs two communication systems and how they interlock.

Priority labels: Must know = cold; Know the logic = mechanism not names; Passage-level = recognize, don't memorize; Optional = skippable.

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The Endocrine System: Function and Core Definitions

Must know

The endocrine system controls cells, tissues, and organs by releasing hormones directly into the bloodstream (or interstitial fluid) — "secreting inward," not into a duct.

The three secretion modes:

Type	Route	Example
Endocrine	Into blood; distant target	Insulin → muscle
Paracrine	Into interstitial fluid; nearby target	Prostaglandins at injury site
Autocrine	Onto the secreting cell itself	Some growth factors

An endocrine gland is ductless and secretes into the blood — the contrast with exocrine glands, which secrete through ducts onto surfaces (salivary, sweat, exocrine pancreas). A hormone is recognized by specific receptors on target cells; receptor specificity is what makes the system precise even though the hormone bathes every tissue.

Passage-level

Eicosanoids: prostaglandins, thromboxanes, and leukotrienes are lipid-derived local (paracrine/autocrine) signals made from arachidonic acid via cyclooxygenase (COX). NSAIDs (aspirin, ibuprofen) inhibit COX → less prostaglandin synthesis — this link is tested directly.

Quick check: A patient takes a high dose of aspirin. Which class of signaling molecule is most directly reduced, and through what enzyme pathway?

Answer: Prostaglandin (and thromboxane) synthesis is reduced because aspirin inhibits COX-1 and COX-2, blocking conversion of arachidonic acid to these eicosanoids.

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Major Types of Hormones

A hormone's chemistry determines how it works — how it enters cells, where its receptor lives, and how fast it acts. The MCAT tests this mechanistic chain.

Peptide (Protein) Hormones

Must know

Built from amino acids and water-soluble, so they cannot cross the membrane. Their receptors are on the cell surface (GPCRs or receptor tyrosine kinases), and they act through second-messenger cascades (cAMP/PKA or IP₃/DAG) that amplify the signal — which is why hormones work at nanomolar concentrations. Key point: peptide hormones act fast, at the cell surface, via second messengers. (Cascade details: Biosignaling guide.)

Steroid Hormones

Must know

Derived from cholesterol and lipid-soluble, so they diffuse through the membrane and bind intracellular receptors. The hormone-receptor complex acts as a transcription factor, altering gene expression. Consequences:

• Slow onset (hours) — new proteins must be made; longer duration
• No second messenger needed
• Carried in blood bound to carrier proteins (lipid-soluble → needs a carrier to stay in solution)

Steroid-producing glands: adrenal cortex, gonads (testes → testosterone; ovaries → estrogens, progesterone), placenta (pregnancy).

Know the logic

Adrenal cortex zones, "Salt, Sugar, Sex" (outer → inner): zona glomerulosa → mineralocorticoids (aldosterone, salt); zona fasciculata → glucocorticoids (cortisol, sugar); zona reticularis → androgens (DHEA, sex).

Quick check: Why does cortisol take hours to suppress inflammation, while epinephrine relieves bronchoconstriction in minutes?

Answer: Cortisol is a steroid that must enter cells, bind nuclear receptors, and alter transcription — slow. Epinephrine is a water-soluble catecholamine acting on cell-surface receptors with instant second-messenger activation — no new protein synthesis.

Amino Acid–Derived Hormones

Must know

Solubility and mechanism vary, which is why the MCAT tests these carefully.

• Catecholamines (epinephrine, norepinephrine, dopamine), from tyrosine: water-soluble, cell-surface receptors, fast. Behave like peptide hormones.
• Thyroid hormones (T₃, T₄), also from tyrosine but iodinated → lipid-soluble: cross the membrane, nuclear receptors, behave like steroids. Classic MCAT trap (see Common Confusions).
• Melatonin, from tryptophan (pineal gland): lipid-soluble.

Class	Derived From	Solubility	Receptor	Speed
Peptide/protein	Amino acids	Water-soluble	Cell surface	Fast
Steroid	Cholesterol	Lipid-soluble	Intracellular	Slow
Catecholamines	Tyrosine	Water-soluble	Cell surface	Fast
Thyroid (T₃/T₄)	Tyrosine + iodine	Lipid-soluble	Nuclear	Slow
Melatonin	Tryptophan	Lipid-soluble	Intracellular	Slow

Quick check: A newly discovered hormone is derived from cholesterol and increases gene transcription. Where is its receptor, and would it need a carrier protein in blood?

Answer: Intracellular (nuclear/cytoplasmic), because cholesterol-derived = steroid = lipid-soluble. Being lipid-soluble, it would need a plasma carrier protein to stay in solution.

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Major Endocrine Glands: Names, Locations, and Products

Fact-dense but directly tested. Map from the top of the body downward.

Hypothalamus

Must know

Location: floor of the third ventricle, above the pituitary.

The bridge between nervous and endocrine systems and the master regulator of the pituitary. It releases hormones through the hypothalamic-pituitary portal system directly to the anterior pituitary (so tiny amounts act without systemic dilution).

Know the logic

Releasing/inhibiting hormones (all peptides). Know the pattern (each controls a specific pituitary hormone); don't drill the abbreviations cold:

Hormone	Effect on Anterior Pituitary
GnRH	Stimulates FSH and LH
TRH	Stimulates TSH (and prolactin)
CRH	Stimulates ACTH
GHRH	Stimulates GH
Somatostatin	Inhibits GH (and TSH)
Dopamine	Inhibits prolactin

The hypothalamus also synthesizes ADH (vasopressin) and oxytocin, stored/released by the posterior pituitary.

Pituitary Gland (Hypophysis)

Must know

Location: sella turcica, directly below the hypothalamus. Two distinct lobes.

Anterior Pituitary (Adenohypophysis)

Must know

A true endocrine gland — synthesizes its own hormones in response to hypothalamic signals. Products (all peptides):

Hormone	Target	Key Action
GH (somatotropin)	Liver, muscle, bone	Stimulates IGF-1; growth, lipolysis, anti-insulin
TSH	Thyroid	Stimulates T₃/T₄
ACTH	Adrenal cortex	Stimulates cortisol
FSH	Gonads	Follicle development (♀), spermatogenesis (♂)
LH	Gonads	Ovulation (♀), testosterone (♂)
Prolactin	Mammary glands	Milk production

FSH and LH are gonadotropins; TSH, ACTH, and GH are tropic (stimulate other glands). GH also acts on many tissues directly.

Posterior Pituitary (Neurohypophysis)

Must know

Not a true gland — neural tissue (hypothalamic axons) that stores and releases (does not synthesize) two peptides made in the hypothalamus:

• ADH (vasopressin): released when plasma osmolarity rises or blood volume falls. Inserts aquaporin-2 in kidney collecting ducts → water reabsorption → concentrated urine. Also vasoconstriction at high doses.
• Oxytocin: uterine contractions in labor (positive feedback) and milk let-down.

Quick check: A tumor destroys the posterior pituitary. Which two hormones are lost, and what is the main consequence of losing ADH?

Answer: ADH and oxytocin. Without ADH, collecting ducts can't reabsorb water → large volumes of dilute urine and dehydration (central diabetes insipidus — distinct from diabetes mellitus, which involves insulin).

Thyroid Gland

Must know

Location: anterior neck, wrapped around the trachea.

• T₃ / T₄: made by follicular cells by iodinating tyrosine; T₄ is the major secretory form, converted peripherally to the more active T₃. Both require iodine (deficiency → goiter). They raise basal metabolic rate and O₂ consumption and are essential for growth and brain development.
• Calcitonin (parafollicular C cells): lowers blood calcium by inhibiting osteoclasts. Minor vs. PTH but tested.

Parathyroid Glands

Must know

Location: four small glands on the posterior thyroid.

PTH is the dominant regulator of plasma calcium. Released when $\ce{Ca^{2+}}$ falls, it: (1) stimulates osteoclasts to resorb bone, (2) increases renal $\ce{Ca^{2+}}$ reabsorption, (3) stimulates renal calcitriol (active vitamin D₃) → more intestinal $\ce{Ca^{2+}}$ absorption. PTH and calcitonin are antagonists: PTH raises calcium, calcitonin lowers it.

Quick check: A patient has their thyroid surgically removed and hours later develops muscle spasms and tetany. Explain.

Answer: The parathyroids (on the posterior thyroid) were likely removed too. Without PTH → hypocalcemia → reduced threshold for motor neuron firing → tetany.

Adrenal Glands

Must know

Location: atop each kidney. Two functionally distinct regions.

Adrenal Cortex (steroids from cholesterol, "Salt, Sugar, Sex"):

• Aldosterone (mineralocorticoid): reabsorbs $\ce{Na+}$ (and water), excretes $\ce{K+}$. Regulated by the renin-angiotensin-aldosterone system (RAAS) and high plasma $\ce{K+}$ — not mainly ACTH.
• Cortisol (glucocorticoid): raises blood glucose (gluconeogenesis), suppresses immune/inflammatory response. Released via ACTH and stress; inhibits CRH/ACTH (negative feedback).
• Androgens (DHEA): weak; contribute to secondary sex characteristics, especially in females.

Adrenal Medulla (neural crest origin): chromaffin cells — modified postganglionic sympathetic neurons — release epinephrine (~80%) and norepinephrine into blood on sympathetic stimulation, mediating fight-or-flight (↑heart rate, bronchodilation, glycogenolysis, lipolysis).

Pancreas

Must know

Location: retroperitoneal, behind the stomach. Both exocrine (digestive enzymes) and endocrine (islets of Langerhans):

• α cells → glucagon: raises blood glucose (hepatic glycogenolysis, gluconeogenesis)
• β cells → insulin: lowers blood glucose (glucose uptake into muscle/fat, glycogen synthesis)
• δ cells → somatostatin: inhibits both insulin and glucagon (paracrine)

Both are peptide hormones on cell-surface receptors. Insulin's receptor is a receptor tyrosine kinase (RTK) — a key MCAT exception.

Quick check: A type 1 diabetic has no functional β cells. Would plasma glucagon be elevated or depressed, and why?

Answer: Elevated. Insulin normally suppresses glucagon via paracrine signaling in the islets; without it, that inhibition is lost → glucagon rises, worsening hyperglycemia.

Gonads

Must know

• Testes (Leydig cells): testosterone (steroid) in response to LH → spermatogenesis, secondary sex characteristics, anabolic effects. Sertoli cells make inhibin (negative feedback on FSH).
• Ovaries: estrogens (estradiol) and progesterone (steroids). Estrogen drives follicle development and the mid-cycle LH surge (positive feedback — key exception). Progesterone, from the corpus luteum, maintains the uterine lining. Inhibin feeds back on FSH.

Pineal Gland

Passage-level

Location: epithalamus. Produces melatonin (from tryptophan) in a circadian rhythm, peaking at night; regulates sleep-wake cycles. Light (via the suprachiasmatic nucleus) suppresses it.

Thymus

Passage-level

Produces thymosin → T lymphocyte maturation; active in childhood. Mainly tested as an immune organ.

Kidney and Other Tissues

Know the logic

Non-classic tissues that secrete hormones:

• Kidneys: erythropoietin (EPO) with hypoxia → RBC production; calcitriol (active vitamin D); renin (initiates RAAS).
• Heart: atrial natriuretic peptide (ANP) with atrial stretch → renal Na⁺/water excretion → lowers BP (antagonizes RAAS).
• Liver: IGF-1, which mediates most of GH's anabolic effects.
• Adipose: leptin → satiety signal to the hypothalamus.

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Neuroendocrinology: The Nervous System–Endocrine Interface

How the nervous and endocrine systems talk — tested several ways.

The Hypothalamus as the Neuroendocrine Integrator

Must know

The hypothalamus converts neural input (sensory, stress, circadian) into hormonal output. Its neurosecretory cells fire action potentials but release peptide hormones into blood rather than synaptic clefts.

The H-P-target organ axes:

• HPA: Hypothalamus (CRH) → pituitary (ACTH) → adrenal cortex (cortisol) → negative feedback
• HPT: TRH → TSH → thyroid (T₃/T₄) → negative feedback
• HPG: GnRH → FSH/LH → gonads (sex steroids) → negative feedback (except mid-cycle estrogen positive feedback → LH surge)

The Adrenal Medulla: A Neural-Endocrine Hybrid

Must know

Chromaffin cells (neural crest) are modified postganglionic sympathetic neurons that release catecholamines into blood. They are innervated by preganglionic sympathetic fibers (ACh → nicotinic receptors). So fight-or-flight is simultaneously neural and endocrine.

Neurotransmitters Acting as Hormones

Know the logic

• Norepinephrine: neurotransmitter at sympathetic synapses; hormone from adrenal medulla
• Dopamine: brain neurotransmitter; hypothalamic hormone controlling prolactin
• ADH and oxytocin: released from neural terminals (posterior pituitary) into blood — the purest neurosecretion

Feedback Loops: Negative and Positive

Must know

Almost all axes use negative feedback (set-point regulation). The two tested positive feedback examples: (1) the LH surge — rising estrogen stimulates a massive LH pulse → ovulation (switches back to negative feedback once progesterone dominates); (2) oxytocin in labor — contractions → stretch → more oxytocin → stronger contractions, until delivery.

Quick check: A patient takes synthetic glucocorticoid (prednisone) for months, then abruptly stops. Why might they develop adrenal crisis (dangerously low cortisol)?

Answer: Chronic exogenous glucocorticoid → prolonged negative feedback (↓CRH, ↓ACTH) → atrophy of the zona fasciculata. On abrupt stop, the HPA axis can't recover fast enough and endogenous cortisol is insufficient — a potentially life-threatening crisis.

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Common Confusions & Tricks

1. Anterior vs. posterior pituitary — synthesis vs. storage. The anterior pituitary makes its hormones (FSH, LH, GH, TSH, ACTH, prolactin). The posterior pituitary (neural tissue) stores and releases hypothalamic hormones (ADH, oxytocin). "Destroyed posterior pituitary" → ADH/oxytocin loss, not FSH or ACTH.

2. Thyroid hormones are NOT steroids but behave like them. T₃/T₄ are tyrosine-derived, so students assume they act like epinephrine (fast, cell-surface). Wrong — iodination makes them lipophilic → nuclear receptors, slow, steroid-like. For T₃/T₄ receptor location, answer: intracellular/nuclear.

3. Cortisol vs. aldosterone. Both adrenal-cortex steroids affecting the kidney. Aldosterone → Na⁺ retention/K⁺ excretion → BP/volume (regulated by RAAS and plasma K⁺). Cortisol → glucose metabolism, immune suppression, stress (regulated by ACTH).

4. PTH raises calcium; calcitonin lowers it — but PTH dominates. Calcitonin plays a minor day-to-day role. For any hyper-/hypocalcemia question, think PTH first.

5. Epinephrine vs. norepinephrine. Both catecholamines from the adrenal medulla. Epinephrine acts on both α and β (more bronchodilation/cardiac stimulation); norepinephrine is preferentially α (more vasoconstriction).

6. "Tropic" hormones target other endocrine glands. ACTH, TSH, FSH, LH are tropic. GH and prolactin have direct tissue targets.

7. Insulin receptor is an RTK, not a GPCR. Most peptide hormones use GPCRs; insulin (and IGF-1) is the major MCAT exception — binding triggers autophosphorylation. "Hormone activates a tyrosine kinase on binding" → think insulin.

8. Negative feedback is the default; positive is the exception. The two positive-feedback cases: (1) LH surge from rising estrogen, (2) oxytocin in labor.

9. Adrenal medulla is sympathetic, but its synaptic neurotransmitter is ACh. Preganglionic fibers release ACh onto chromaffin cells (nicotinic receptors); the chromaffin cells then release epinephrine/NE into blood.

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Key Regulatory Relationships

This is a structure/function/regulation topic — no equations to memorize. The high-yield regulatory schemes:

Relationship	What to Know
$\ce{PTH \uparrow \implies [Ca^{2+}]_{plasma} \uparrow}$; $\ce{Calcitonin \uparrow \implies [Ca^{2+}]_{plasma} \downarrow}$	PTH via osteoclasts, kidney, calcitriol; calcitonin inhibits osteoclasts
$\ce{Angiotensinogen ->[\text{renin}] Ang I ->[\text{ACE}] Ang II -> Aldosterone}$	Ang II stimulates zona glomerulosa; aldosterone → renal $\ce{Na+}$ retention
$\ce{T4 ->[\text{deiodinase}] T3}$	Peripheral conversion; T₃ is the more potent form
HPA negative feedback: $\text{Cortisol} \dashv \text{CRH} \dashv \text{ACTH}$	High cortisol suppresses the upstream axis
$\uparrow\text{plasma osmolarity} \Rightarrow \uparrow\text{ADH} \Rightarrow \uparrow\text{aquaporin-2} \Rightarrow \downarrow\text{urine output}$	Rising osmolarity drives ADH; ADH concentrates urine