Module 6: The Endocrine System

AAMC Content Category 3A: Structure and Function of the Endocrine System on the MCAT

The MCAT tests endocrine system concepts as part of AAMC Content Category 3A, which emphasizes how internal organs and systems coordinate to maintain homeostasis. This module focuses on the structure and function of the major endocrine glands, the hormones they produce, and the mechanisms of hormonal signaling. Students are expected to understand feedback regulation (especially negative feedback), the difference between peptide and steroid hormones, and the physiological roles of key axes such as the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) systems. Mastery of the endocrine system is essential for interpreting hormone-related pathways in MCAT passages, particularly those involving metabolism, reproduction, and stress response.

Introduction to the Endocrine System

The endocrine system is a major regulatory system of the human body, responsible for coordinating many long-term processes by secreting hormones into the bloodstream. Unlike the nervous system, which offers rapid and short-lived responses via electrical signals, the endocrine system communicates more slowly but produces sustained effects that regulate metabolism, growth, development, reproduction, and homeostasis.

Hormones are chemical messengers produced by endocrine glands and transported through the circulatory system to target organs. Each hormone binds specific receptors and elicits changes in cellular activity. Because hormones act at a distance and their effects are slower, they are particularly well-suited for widespread and prolonged physiological adjustments.

The system is tightly regulated through feedback mechanisms, particularly negative feedback loops, to ensure stable internal conditions. Many hormonal pathways are initiated or modulated by the brain, especially through structures such as the hypothalamus and pituitary gland. This connection between the nervous and endocrine systems forms the basis of neuroendocrine regulation.

Types of Cell Signaling

To understand endocrine communication, it’s helpful to contrast it with other types of cell-to-cell signaling:

Types of Cell Signaling (MCAT High-Yield)

Signaling Type	Definition	Example
Endocrine	Hormones are released into the bloodstream and act on distant target cells	Insulin released by pancreas affects glucose uptake in muscle
Paracrine	Secreted molecules act on neighboring cells within the same tissue	Somatostatin from δ-cells inhibits nearby α- and β-cells in the pancreas
Autocrine	Cells respond to their own secretions	Activated T cells release IL-2, stimulating their own proliferation
Juxtacrine	Requires direct cell-to-cell contact; signals are transmitted via membrane-bound molecules	Notch signaling in embryonic development

MCAT Tip: The MCAT may ask you to classify a signaling interaction based on distance, signal type, or method of delivery—memorize the distinctions

Hormone Classification & Mechanisms of Action

Hormones can be classified by their chemical structure and mechanism of receptor interaction. This classification determines how they travel in the blood, how they interact with target cells, and how quickly they act.

A. Types of Hormones (by Structure)

Hormone Type	Structure	Solubility	Transport	Receptor Location	Examples
Peptide/Protein	Chains of amino acids	Hydrophilic	Dissolved in plasma	Cell surface receptors	Insulin, Glucagon, ADH
Steroid	Derived from cholesterol	Lipophilic	Bound to carrier proteins	Intracellular receptors	Cortisol, Aldosterone, Estrogen
Amino Acid Derivatives	Modified amino acids	Mixed (depends on molecule)	Mixed	Cell surface or intracellular	Epinephrine (surface), Thyroxine (intracellular)

B. Mechanism of Action

• Peptide hormones bind to cell surface receptors and activate second messengers (e.g., cAMP, IP₃). Their effects are rapid but short-lived.
• Steroid hormones pass through the cell membrane and bind intracellular receptors, altering gene expression. Effects are slower but longer-lasting.
• Amino acid derivatives can act like either peptide (e.g., epinephrine via GPCRs) or steroid hormones (e.g., thyroxine affecting transcription).

C. Hormone Type Comparison: Speed, Duration, and MCAT Tie-In

Hormone Type	Speed of Action	Duration	MCAT Relevance
Peptide	Fast	Short-term	Know second messenger pathways (e.g., cAMP, IP₃/DAG)
Steroid	Slow	Long-term	Genomic effects; transcription and translation regulation
Amino Acid Derivatives	Variable	Variable	Distinguish fast-acting (e.g., epinephrine) from slow (e.g., thyroxine)

MCAT Endocrine System Tip: The MCAT frequently tests hormone classification, receptor type, and downstream effects. Know which hormones act via cAMP (e.g., glucagon), vs. those that act via gene transcription (e.g., cortisol).

Endocrine Organs and Their Hormones

The human endocrine system consists of specialized glands that produce and secrete hormones directly into the bloodstream. Each gland serves specific physiological functions and communicates with others through hormonal feedback loops. The hypothalamus-pituitary axis acts as the master regulator, coordinating signals between the brain and peripheral glands.

A. Major Endocrine Glands and Their Hormones

Gland	Key Hormones	Function
Hypothalamus	TRH, CRH, GnRH, GHRH, somatostatin, dopamine	Regulates pituitary hormone release
Anterior Pituitary	ACTH, TSH, LH, FSH, GH, Prolactin	Stimulates peripheral glands; growth and reproduction
Posterior Pituitary	ADH (vasopressin), Oxytocin	Water retention; uterine contractions, lactation
Pineal Gland	Melatonin	Regulates circadian rhythm
Thyroid Gland	T₃ (triiodothyronine), T₄ (thyroxine), Calcitonin	Metabolism regulation; lowers blood calcium
Parathyroid Glands	PTH (parathyroid hormone)	Increases blood calcium levels
Adrenal Cortex	Cortisol, Aldosterone, Androgens	Stress response, blood pressure control, secondary sex characteristics
Adrenal Medulla	Epinephrine, Norepinephrine	Mediates sympathetic nervous system response (“fight-or-flight”)
Pancreas (Islets)	Insulin, Glucagon, Somatostatin	Blood glucose regulation
Ovaries/Testes	Estrogen, Progesterone, Testosterone	Control of sexual development and reproductive functions

B. Hypothalamic-Pituitary Axis

This axis governs the activity of several peripheral endocrine glands through tropic hormones. It’s structured in a three-tiered hierarchy:

1. Hypothalamus secretes releasing or inhibiting hormones (e.g., TRH, CRH).
2. These act on the anterior pituitary, which releases tropic hormones (e.g., TSH, ACTH).
3. These, in turn, stimulate peripheral glands (e.g., thyroid, adrenal cortex) to release their target hormones.

MCAT Endocrine System Tip: Know which hormones come from the anterior vs. posterior pituitary, and understand negative feedback loops (e.g., cortisol inhibits CRH and ACTH).

Mnemonics for the Pituitary Gland

Anterior Pituitary Hormones – “FLAT PEG”

This classic MCAT mnemonic helps you remember the seven hormones secreted by the anterior pituitary.

Anterior Pituitary Hormones (FLAT PEG)

Letter	Hormone	Type	Primary Function
F	FSH – Follicle-Stimulating Hormone	Tropic	Stimulates gamete production in ovaries (oogenesis) and testes (spermatogenesis)
L	LH – Luteinizing Hormone	Tropic	Triggers ovulation in females; stimulates testosterone production in males
A	ACTH – Adrenocorticotropic Hormone	Tropic	Stimulates cortisol (glucocorticoid) secretion from the adrenal cortex
T	TSH – Thyroid-Stimulating Hormone	Tropic	Stimulates thyroid to produce and release T₃ and T₄ hormones
P	Prolactin	Direct	Promotes milk production in mammary glands
E	Endorphins	Direct	Natural pain suppression (e.g., β-endorphin); minimally tested on MCAT
G	GH – Growth Hormone	Direct	Stimulates growth and cell reproduction via IGF-1 secretion from the liver

MCAT Endocrine System Tip:

• FLAT = Tropic hormones (regulate other endocrine glands)
• PEG = Direct hormones (act directly on target tissues)

Posterior Pituitary Hormones – “AO”

(short for Antidiuretic and Oxytocin) These hormones are synthesized in the hypothalamus and released by the posterior pituitary:

Posterior Pituitary Hormones (Mnemonic: A&O)

Letter	Hormone	Full Name	Primary Function
A	ADH	Antidiuretic Hormone (aka Vasopressin)	Increases water reabsorption in the kidneys (collecting ducts); concentrates urine; raises blood pressure via vasoconstriction
O	Oxytocin	—	Stimulates uterine contractions during labor and milk ejection during breastfeeding

MCAT Endocrine System Tip:
The posterior pituitary does not synthesize hormones — it only stores and secretes ADH and oxytocin, both made in the hypothalamus (supraoptic and paraventricular nuclei).

Feedback Mechanisms in Hormonal Regulation

The endocrine system relies heavily on feedback loops to maintain homeostasis. These loops adjust hormone secretion in response to the body’s needs. The MCAT expects you to understand the direction of feedback (positive vs. negative), recognize hierarchical regulation (e.g., hypothalamus → pituitary → gland), and interpret questions involving abnormal hormone levels (e.g., primary vs. secondary disorders).

A. Negative Feedback (Most Common)

In a negative feedback loop, the final hormone or its physiological effect inhibits its own production pathway. This prevents overactivation and maintains a stable internal environment.

Example: Hypothalamic-Pituitary-Adrenal (HPA) Axis

1. Hypothalamus releases CRH
2. → Anterior Pituitary releases ACTH
3. → Adrenal Cortex releases Cortisol
4. → Cortisol inhibits both CRH and ACTH release (negative feedback)

MCAT Endocrine System Tie-In: If cortisol is high but CRH and ACTH are low, the problem lies in the adrenal cortex (primary disorder). If all are elevated, suspect a hypothalamic or pituitary tumor (secondary disorder).

HPA Axis – The Stress Response

Hormonal Cascade:
CRH (Hypothalamus) → ACTH (Anterior Pituitary) → Cortisol (Adrenal Cortex)

Negative Feedback:
Cortisol inhibits both CRH and ACTH release to maintain homeostasis.

Triggers:

• Physical or emotional stress
• Hypoglycemia (low blood glucose)

Major Physiological Effects of Cortisol:

• ↑ Gluconeogenesis (raises blood glucose)
• ↓ Immune response (anti-inflammatory)
• ↑ Blood pressure
• Promotes lipolysis and protein catabolism

MCAT Favorite: Identify dysfunction (e.g., pituitary tumor → ↑ACTH, ↑Cortisol)

B. Positive Feedback (Less Common)

Here, a hormone’s action amplifies its own production, usually in situations requiring rapid, self-reinforcing effects.

Example: Oxytocin in Labor

• Uterine contractions → release of oxytocin → more contractions → more oxytocin
• Ends only after childbirth interrupts the loop

MCATEndocrine System Tie-In: Know oxytocin and LH surge during ovulation as exceptions to negative feedback dominance.

C. Hierarchical Dysregulation (MCAT-Favorite)

The MCAT may test disorders by asking which hormone levels would increase or decrease. Here’s a quick-reference table:

Endocrine Axis Dysfunction – Levels and Hormone Patterns

Level of Dysfunction	Location of Problem	Example	Hormone Levels
Primary	Peripheral gland	Adrenal tumor	Cortisol ↑, ACTH ↓, CRH ↓
Secondary	Pituitary	ACTH-secreting adenoma	Cortisol ↑, ACTH ↑, CRH ↓
Tertiary	Hypothalamus	Excess CRH production	CRH ↑, ACTH ↑, Cortisol ↑

MCAT Endocrine System Tip: Always trace hormone levels upstream and downstream when analyzing endocrine disorders.

Hormonal Regulation of Metabolism

Metabolic processes like glucose homeostasis, lipid mobilization, and basal metabolic rate are under tight hormonal control. The MCAT frequently tests the physiological actions and interplay of key metabolic hormones, especially in the context of fed vs. fasting states and stress response.

A. Glucose Regulation: Insulin and Glucagon

The pancreas plays a central role in maintaining blood glucose homeostasis by releasing two antagonistic hormones:

Pancreatic Hormones – Glucose Regulation

Hormone	Source	Trigger	Primary Effects
Insulin	β-cells of pancreas	High blood glucose (e.g., after a meal)	↑ Glucose uptake (esp. muscle, fat), ↑ glycogenesis, ↑ lipogenesis; ↓ gluconeogenesis
Glucagon	α-cells of pancreas	Low blood glucose (e.g., fasting state)	↑ Glycogenolysis, ↑ gluconeogenesis, ↑ lipolysis

Insulin facilitates anabolic processes, while glucagon promotes catabolic pathways to restore glucose levels. Their antagonistic actions ensure glucose availability during both feeding and fasting.

MCAT Endocrine System Tip: Know which metabolic processes are insulin-dependent (e.g., GLUT4-mediated glucose uptake in muscle and adipose tissue).

B. Stress Response: Cortisol and Epinephrine

Under physical or emotional stress, the body activates the HPA axis and sympathetic nervous system to mobilize energy resources.

• Cortisol (from adrenal cortex):
  • Increases gluconeogenesis
  • Mobilizes amino acids and lipids for energy
  • Suppresses immune and inflammatory responses
• Epinephrine (from adrenal medulla):
  • Increases heart rate and blood pressure
  • Stimulates glycogen breakdown and lipolysis
  • Dilates airways to increase oxygen delivery

These hormones prepare the body for “fight or flight” by increasing blood glucose and energy substrate availability.

MCAT Endocrine System Tip: Cortisol works over a longer duration, while epinephrine acts rapidly. Both contribute to elevated glucose levels during acute stress.

C. Basal Metabolic Rate: Thyroid Hormones

Thyroid hormones play a crucial role in regulating overall metabolic rate:

• Thyroxine (T₄) and Triiodothyronine (T₃) (from thyroid gland):
  • Increase oxygen consumption and heat production (thermogenesis)
  • Stimulate mitochondrial activity and protein synthesis
  • Enhance effects of catecholamines (epinephrine/norepinephrine)

Thyroid hormones are essential for normal growth, brain development, and metabolic balance.

MCAT Endocrine System Tip: T₃ is the more biologically active form; T₄ is a prohormone converted to T₃ in peripheral tissues.

HPT Axis – Thyroid Regulation

Hormonal Cascade:
TRH (Hypothalamus) → TSH (Anterior Pituitary) → T₃/T₄ (Thyroid Gland)

Negative Feedback:
T₃ and T₄ inhibit TRH and TSH to regulate hormone levels.

Hypothyroidism:

• ↓ T₃/T₄ → ↑ TRH, ↑ TSH (due to loss of negative feedback)
• Common causes: iodine deficiency, Hashimoto’s thyroiditis

Hyperthyroidism (e.g., Graves Disease):

• Autoantibodies stimulate TSH receptors
• ↑ T₃/T₄, ↓ TSH (due to suppressed pituitary signaling)

Summary Table: Hormonal Control of Metabolism

Hormone	Origin	Effect on Glucose	Effect on Lipids	Metabolic Role
Insulin	Pancreatic β-cells	↓ Glucose (↑ uptake, ↑ storage)	↑ Lipid synthesis (lipogenesis)	Anabolic – Promotes energy storage
Glucagon	Pancreatic α-cells	↑ Glucose (via glycogenolysis & gluconeogenesis)	↑ Lipolysis	Catabolic – Fasting fuel mobilization
Cortisol	Adrenal cortex	↑ Glucose (↑ gluconeogenesis)	↑ Fat & protein breakdown	Long-term stress adaptation
Epinephrine	Adrenal medulla	↑ Glucose (↑ glycogenolysis, ↑ gluconeogenesis)	↑ Lipolysis	Short-term stress (fight-or-flight)
T₃ / T₄	Thyroid gland	Mild ↑ (↑ metabolism, ↑ glucose turnover)	↑ Lipid turnover	Regulates BMR, growth, and development

Hormonal Control of Calcium, Fluid, and Electrolyte Balance

Maintaining appropriate levels of calcium, fluids, and electrolytes is vital for nerve transmission, muscle contraction, enzyme activity, and overall homeostasis. Several hormones work in concert to regulate these components across organs like bone, kidney, and intestine.

A. Calcium Homeostasis: PTH, Calcitonin, and Vitamin D

Hormone	Source	Trigger	Primary Effects
Parathyroid Hormone (PTH)	Parathyroid glands	Low serum calcium	Increases bone resorption, enhances Ca²⁺ reabsorption in kidney, activates vitamin D
Calcitonin	Thyroid (C cells)	High serum calcium	Inhibits bone resorption, promotes calcium deposition in bone
Calcitriol (Active Vitamin D)	Kidney (via activation of dietary vitamin D)	PTH stimulation or low Ca²⁺	Increases intestinal absorption of calcium and phosphate

• PTH is the primary hormone regulating serum calcium levels. It raises blood calcium by stimulating bone breakdown, reducing urinary loss, and enhancing vitamin D activation.
• Calcitonin opposes PTH, promoting bone formation and reducing serum calcium.
• Vitamin D increases calcium absorption from the gut and is essential for proper mineralization of bone.

MCAT Tip: Know that PTH increases blood calcium, while calcitonin decreases it. Vitamin D enhances calcium absorption but also depends on PTH for activation.

B. Fluid and Electrolyte Balance: ADH and Aldosterone

Hormone	Source	Trigger	Effect on Fluid/Electrolytes
ADH (Vasopressin)	Posterior pituitary	High plasma osmolality or low blood volume	Increases water reabsorption in kidney collecting ducts (via aquaporins), concentrating urine
Aldosterone	Adrenal cortex (zona glomerulosa)	Low blood pressure (via RAAS), high K⁺	Increases Na⁺ reabsorption and K⁺ excretion in distal tubules and collecting ducts

• ADH helps retain water to combat dehydration and blood volume loss, acting on collecting ducts to insert aquaporins.
• Aldosterone conserves sodium (and thus water) while promoting potassium excretion, essential for blood pressure regulation.

MCAT Endocrine System Tip: ADH controls water only, while aldosterone affects salt and water. This distinction is often tested in fluid balance scenarios.

Reproductive Hormones and Sexual Development

The endocrine system plays a critical role in regulating human sexual development, puberty, gametogenesis, and reproductive function. These processes are orchestrated by interactions between the hypothalamus, pituitary gland, and gonads, collectively forming the hypothalamic-pituitary-gonadal (HPG) axis.

A. The Hypothalamic-Pituitary-Gonadal (HPG) Axis

• The hypothalamus releases Gonadotropin-Releasing Hormone (GnRH) in a pulsatile manner.
• GnRH stimulates the anterior pituitary to release two gonadotropins:
  • Luteinizing Hormone (LH)
  • Follicle-Stimulating Hormone (FSH)
• LH and FSH then act on the gonads (testes or ovaries) to promote gamete production and sex hormone secretion.

MCAT Tip: The pulsatile nature of GnRH is critical. Continuous GnRH suppresses LH/FSH secretion (basis for certain hormone therapies).

HPG Axis Summary

GnRH → stimulates FSH & LH → act on gonads

Gonadotropins: FSH and LH Actions in Males vs. Females

Target	FSH Action	LH Action	Hormone Product(s)
Testes (Males)	Stimulates Sertoli cells → spermatogenesis	Stimulates Leydig cells → testosterone synthesis	Testosterone
Ovaries (Females)	Stimulates follicular growth → estrogen production	Triggers ovulation, supports corpus luteum	Estrogen (follicular phase), Progesterone (luteal phase)

Inhibin: Feedback inhibition on FSH

MCAT Tie-in: Predict hormone levels in infertility or endocrine tumors

B. Male Reproductive Hormones

Hormone	Source	Target	Function
GnRH	Hypothalamus	Anterior pituitary	Stimulates LH and FSH release
FSH	Anterior pituitary	Sertoli cells (testes)	Supports spermatogenesis, stimulates inhibin secretion
LH	Anterior pituitary	Leydig cells (testes)	Stimulates testosterone production
Testosterone	Leydig cells (testes)	Various tissues	Promotes male secondary sex characteristics, libido, and muscle mass

• Inhibin, secreted by Sertoli cells, provides negative feedback on FSH.
• Testosterone also inhibits both hypothalamus (GnRH) and anterior pituitary (LH/FSH), closing the loop.

MCAT Endocrine System Tip: FSH = spermatogenesis (Sertoli); LH = testosterone (Leydig). Know the cell-type targets.

C. Female Reproductive Hormones and the Menstrual Cycle

The menstrual cycle is a tightly regulated, recurring ~28-day sequence of hormonal events that prepares the female body for the possibility of fertilization and pregnancy. It is governed by hormonal interactions between the hypothalamus, anterior pituitary gland, and ovaries, involving several feedback mechanisms that regulate the maturation of ovarian follicles, ovulation, endometrial thickening, and menstrual shedding.

The cycle is divided into three major phases:

1. Follicular Phase (Days 1–13)
2. Ovulation (Day 14)
3. Luteal Phase (Days 15–28)
   (Day counts are averages; actual cycle lengths may vary.)

Hormonal Regulation – Female Reproductive Axis

Hormone	Source	Target	Main Role
GnRH	Hypothalamus	Anterior Pituitary	Stimulates FSH and LH release
FSH	Anterior Pituitary	Ovarian follicles	Stimulates follicular development
Estrogen	Developing follicles (ovaries)	Uterus, Hypothalamus	Builds endometrium; triggers LH surge via positive feedback
LH	Anterior Pituitary	Mature follicle	Triggers ovulation
Progesterone	Corpus luteum	Uterus, Hypothalamus	Maintains endometrium; inhibits GnRH, FSH, and LH
hCG	Placenta (if fertilization occurs)	Corpus luteum	Maintains corpus luteum → continued progesterone secretion during early pregnancy

Phases of the Menstrual Cycle:

1. Follicular Phase

• Begins on the first day of menstruation and continues until ovulation.
• The hypothalamus secretes GnRH, which stimulates the anterior pituitary to release FSH and LH.
• FSH promotes the maturation of several ovarian follicles; usually only one becomes dominant.
• The growing follicle secretes estrogen, which leads to proliferation of the endometrial lining and initially exerts negative feedback on FSH/LH to prevent overstimulation.

2. Ovulation

• Around day 14, estrogen levels peak. This triggers a positive feedback loop on the hypothalamus and pituitary.
• The result is a surge in LH (and to a lesser extent FSH), which causes:
  • Rupture of the dominant follicle
  • Release of the oocyte (egg) into the fallopian tube
• This is the most fertile window in the cycle.

3. Luteal Phase

• After ovulation, the remnants of the follicle transform into the corpus luteum.
• The corpus luteum secretes progesterone (and some estrogen), which:
  • Maintains and stabilizes the endometrium
  • Exerts negative feedback on GnRH, FSH, and LH to prevent further ovulation
• If fertilization does not occur, the corpus luteum degenerates, leading to:
  • Decreased progesterone and estrogen
  • Shedding of the endometrium → menstruation (start of a new cycle)

4. If Fertilization Occurs

• The developing embryo secretes hCG, which maintains the corpus luteum.
• Progesterone remains elevated, preventing menstruation and allowing pregnancy to continue.

Feedback Loops on the MCAT

• Negative Feedback:
  • Estrogen and progesterone inhibit GnRH, FSH, and LH during most of the cycle.
• Positive Feedback:
  • High estrogen late in follicular phase triggers LH surge.
• Disruption:
  • Tumors, drugs, or lesions affecting GnRH, pituitary function, or ovarian hormone levels can halt or dysregulate the cycle.

MCAT Endocrine System Tip: Know the timing of the LH surge, the role of hCG in pregnancy, and how estrogen’s feedback switches depending on its concentration and timing.

MCAT Mnemonic – “FELOP” for Menstrual Cycle Hormones (in rough sequence):

• FSH
• Estrogen
• LH
• Ovulation
• Progesterone

D. Sexual Differentiation

• All embryos begin with bipotential gonads.
• In XY individuals:
  • SRY gene on Y chromosome triggers testis development.
  • Testes produce:
    • Testosterone → development of male internal/external genitalia.
    • Müllerian Inhibiting Factor (MIF) → regression of female structures.
• In XX individuals:
  • Absence of SRY/testosterone → ovary development and female structures form by default.

MCAT Endocrine System Tip: Know that testosterone and MIF are required for male development. Without them, default development is female.

Neuroendocrine Integration: The Hypothalamus-Pituitary Axis

The endocrine system is deeply intertwined with the nervous system, particularly through the hypothalamic-pituitary axis. This neuroendocrine interface allows the brain to directly regulate hormone production in response to stress, circadian rhythms, temperature, and other internal variables.

The endocrine and nervous systems do not operate independently—they are deeply integrated. This connection is most evident in the hypothalamic-pituitary axis, where the brain directly regulates hormone release via neural and hormonal pathways. The MCAT frequently tests this axis due to its central role in regulating other endocrine glands and coordinating responses to internal and external stimuli.

A. Hypothalamus: The Neuroendocrine Hub

The hypothalamus, located in the diencephalon of the brain, plays a central role in maintaining homeostasis. It continuously monitors key physiological variables such as body temperature, blood osmolarity, stress levels, and circadian rhythms. Based on this input, the hypothalamus regulates both the autonomic nervous system and endocrine function.

To control endocrine outputs, it releases releasing and inhibiting hormones that travel through the hypophyseal portal system to act on the anterior pituitary. In contrast, the posterior pituitary is regulated through direct neural projections from the hypothalamus. Together, these pathways ensure precise hormonal control in response to the body’s internal environment.

Hypothalamic Hormones – MCAT Summary

Hormone	Target	Effect
TRH (Thyrotropin-RH)	Anterior pituitary	Stimulates TSH release
CRH (Corticotropin-RH)	Anterior pituitary	Stimulates ACTH release
GnRH (Gonadotropin-RH)	Anterior pituitary	Stimulates LH and FSH release
GHRH (Growth Hormone-RH)	Anterior pituitary	Stimulates GH (Growth Hormone) release
Somatostatin	Anterior pituitary	Inhibits GH and TSH release
Dopamine (Prolactin Inhibiting Hormone, PIH)	Anterior pituitary	Inhibits prolactin secretion

B. Pituitary Gland: The Master Gland

The pituitary gland, or hypophysis, sits beneath the hypothalamus in the sella turcica of the sphenoid bone. It consists of two distinct lobes:

1. Anterior Pituitary (Adenohypophysis):
   • Synthesizes and secretes tropic hormones that regulate other endocrine glands.
   • Controlled by hypothalamic hormones via the hypophyseal portal system.
2. Posterior Pituitary (Neurohypophysis):
   • Stores and releases hormones synthesized in the hypothalamus.
   • Directly connected via axons from hypothalamic neurons (supraoptic and paraventricular nuclei).

Lobe	Hormones	Primary Function(s)
Anterior	TSH, ACTH, LH, FSH, GH, Prolactin	Tropic hormone regulation of thyroid (TSH), adrenal cortex (ACTH), and gonads (LH, FSH); promotes growth (GH) and lactation (Prolactin)
Posterior	ADH, Oxytocin	Regulates water balance via kidney reabsorption (ADH) and uterine/mammary contractions (Oxytocin)

C. Negative Feedback in the HPA Axis

A hallmark of endocrine signaling is negative feedback, in which rising levels of a hormone reduce the secretion of upstream regulators to maintain homeostasis. This feedback loop prevents excessive hormone secretion and maintains physiological balance.

Example: HPA Axis Feedback

1. Stress → Hypothalamus releases CRH
2. CRH → Pituitary releases ACTH
3. ACTH → Adrenal cortex releases cortisol
4. Cortisol negatively feeds back to inhibit CRH and ACTH release

MCAT Endocrine System Tip: Be prepared to map hormonal cascades from the hypothalamus to peripheral glands and identify where feedback occurs. Negative feedback is the most commonly tested control mechanism.

Major Endocrine Glands – MCAT Summary Table

Gland	Hormones Produced	Primary Functions	MCAT Notes
Hypothalamus	TRH, CRH, GnRH, GHRH, somatostatin, dopamine	Regulates anterior pituitary via releasing and inhibiting hormones	Neuroendocrine interface; key in negative feedback loops with the pituitary
Anterior Pituitary (Adenohypophysis)	ACTH, TSH, LH, FSH, GH, Prolactin	Stimulates peripheral endocrine glands (adrenal, thyroid, gonads); promotes growth, lactation, reproduction	Controlled by hypothalamus via portal system; produces tropic and direct hormones
Posterior Pituitary (Neurohypophysis)	ADH (vasopressin), Oxytocin	Regulates water retention (ADH), uterine contractions, and milk letdown (oxytocin)	Hormones are made in the hypothalamus, stored/released by posterior pituitary (neurosecretory)
Thyroid	T₃, T₄, Calcitonin	Regulates basal metabolic rate (BMR), promotes growth; calcitonin lowers blood calcium	T₃ is more potent than T₄; calcitonin opposes PTH
Parathyroid	PTH (Parathyroid Hormone)	Increases serum calcium via bone resorption, renal reabsorption, and vitamin D activation	PTH activates vitamin D, increases GI calcium absorption; opposes calcitonin
Adrenal Cortex	Cortisol, Aldosterone, Androgens	Manages stress (cortisol), blood pressure/sodium (aldosterone), and sex hormones	Zonal anatomy: Salt (ZG), Sugar (ZF), Sex (ZR)
Adrenal Medulla	Epinephrine, Norepinephrine	Acute stress response (fight or flight) — increases HR, BP, glucose	Part of sympathetic nervous system; secretes catecholamines
Pancreas (Islets of Langerhans)	Insulin, Glucagon, Somatostatin	Maintains glucose homeostasis (insulin ↓, glucagon ↑); somatostatin inhibits secretion	α = glucagon, β = insulin, δ = somatostatin; dysfunction = diabetes mellitus
Pineal Gland	Melatonin	Regulates circadian rhythms and sleep-wake cycle	Secretion is inhibited by light; not a major MCAT focus
Gonads (Testes/Ovaries)	Testosterone, Estrogen, Progesterone, Inhibin	Govern sexual development, menstrual cycle, gamete production	Controlled by FSH/LH from pituitary; feedback with hypothalamus

Feedback Loops Summary (Classic MCAT Endocrine Axes)

1. Hypothalamic-Pituitary-Adrenal (HPA) Axis
   • Hypothalamus: CRH → Pituitary: ACTH → Adrenal cortex: Cortisol
   • Negative feedback: Cortisol inhibits CRH and ACTH release
2. Hypothalamic-Pituitary-Thyroid (HPT) Axis
   • Hypothalamus: TRH → Pituitary: TSH → Thyroid: T3/T4
   • Negative feedback: T3/T4 inhibit TRH and TSH
3. Hypothalamic-Pituitary-Gonadal (HPG) Axis
   • Hypothalamus: GnRH → Pituitary: LH/FSH → Gonads: Estrogen, Testosterone, etc.
   • Negative feedback: Sex hormones inhibit GnRH, LH, FSH
4. GH Axis
   • Hypothalamus: GHRH (stimulates), somatostatin (inhibits) → Pituitary: GH → Liver: IGF-1
   • Negative feedback: IGF-1 inhibits GHRH and GH

Endocrine Axis Overview – MCAT Summary

Axis	Hypothalamic Hormone	Pituitary Hormone	Target Hormone / Gland
HPA	CRH (Corticotropin-RH)	ACTH	Cortisol (Adrenal Cortex) – Stress response
HPT	TRH (Thyrotropin-RH)	TSH	T₃/T₄ (Thyroid) – Metabolic regulation
HPG	GnRH (Gonadotropin-RH)	LH, FSH	Testosterone, Estrogen, Progesterone (Gonads) – Reproduction
GH	GHRH / Somatostatin	GH (Growth Hormone)	IGF-1 (Liver) – Growth and anabolism
PRL	Dopamine (PIH)	Prolactin	Breast tissue – Milk production (no classic third hormone)

Negative Feedback: Target hormones regulate hypothalamus & pituitary

MCAT Endocrine Strategy: Be ready to deduce site of pathology based on hormone levels!

MCAT Strategy Summary

• Know which hormones are peptide (e.g., insulin, ADH), steroid (e.g., cortisol, estrogen), or amino acid-derived (e.g., T3/T4, epinephrine).
• Be prepared to predict hormonal responses to conditions like fasting, dehydration, stress, calcium imbalance, etc.
• Understand target organs, second messengers (cAMP, IP3/DAG), and transport mechanisms (e.g., binding proteins for steroids).
• Apply negative feedback logic to experimental setups or pathophysiology (e.g., hypercortisolism from a pituitary tumor vs. adrenal tumor).