Introduction to the Endocrine System & Hormone Classification

Introduction to the Endocrine System

Hormone Classification · Endocrine vs Exocrine Glands · Chemical Structure

1. Introduction to the Endocrine System & Hormone Classification

The human body utilizes two major types of glandular structures for secretion, distinguished primarily by whether their product travels through a duct or is released directly into the bloodstream.

1.1 Endocrine vs. Exocrine Glands

Gland Type 1
Exocrine Glands
Possess specialized ducts that transport their secretory products (e.g., digestive enzymes, sweat, sebum, saliva) directly into body cavities, the lumen of organs, or onto the epithelial surface of the body.
Gland Type 2
Endocrine Glands
Ductless glands that secrete chemical messengers directly into the interstitial fluid surrounding the secretory cells. From the interstitial space, these molecules diffuse into capillaries and circulate throughout the bloodstream to regulate distant target organs.

Figure: Exocrine vs. Endocrine Secretion Pathways. Exocrine glands route their secretory product through a duct directly onto an epithelial surface or into an organ lumen. Endocrine glands have no duct: the secretory cell releases its product into the surrounding interstitial fluid, from which it diffuses into blood capillaries and is carried by the bloodstream to distant target organs.

1.2 Definition and Nature of Hormones

Concept 1
Classical Definition
Hormones are endocrine signal molecules released by cells of ductless glands into the blood and transported to distantly located target organs.
Concept 2
Modern Scientific Definition
Hormones are low molecular weight, chemically heterogeneous, non-nutrient substances produced in trace amounts that act as intercellular signal molecules.
Concept 3
Target Cell Specificity
Even though hormones circulate throughout the vascular system, only specific target cells respond to a given hormone — because only target cells express specific high-affinity receptor proteins (either on their plasma membrane or intracellularly).
Concept 4
Hormonal Signaling Cascade
Biosynthesis → Storage & Secretion → Vascular Transport → Recognition by Target Receptors → Signal Relay & Amplification (Transduction) → Cellular Response.

1.3 Chemical Classification of Hormones

Hormones are divided into two main solubility classes, which determine their transport mechanism in blood and their cellular mode of action.

Figure: Chemical Hormone Classification. Hormones split first by solubility. Lipid-soluble hormones comprise steroids (cholesterol derivatives) and the iodinated-tyrosine thyroid hormones. Water-soluble hormones comprise amines (modified single amino acids), short peptide chains, and longer proteins & glycoproteins — a distinction that determines how each hormone travels in blood and how it signals its target cell.

1. Lipid-Soluble Hormones

Steroid Hormones — derived from cholesterol; possess a characteristic cyclopentanoperhydrophenanthrene ring structure. Examples: aldosterone, cortisol, androgens, estrogens, and progesterone.
Thyroid Hormones — triiodothyronine (T₃) and tetraiodothyronine (T₄ / thyroxine); synthesized by attaching iodine atoms to the amino acid tyrosine. The nonpolar benzene ring renders them lipid-soluble.

2. Water-Soluble Hormones

Amine Hormones — synthesized by decarboxylation or modification of specific amino acids:
- Tyrosine derivatives: Catecholamines (Epinephrine, Norepinephrine, Dopamine).
- Tryptophan derivatives: Serotonin and Melatonin.
- Histidine derivatives: Histamine.
Peptide Hormones — short amino acid polymers (3 to 49 amino acids). Examples: Antidiuretic Hormone (ADH / Vasopressin), Oxytocin, Melanocyte-Stimulating Hormone (MSH).
Protein Hormones — long amino acid polymers (50 to over 200 amino acids). Examples: Human Growth Hormone (hGH), Insulin.
Glycoprotein Hormones — protein hormones with attached carbohydrate moieties. Examples: Thyroid-Stimulating Hormone (TSH), Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH).

Quick Reference: Lipid-Soluble vs. Water-Soluble Hormones

Property	Lipid-Soluble Hormones	Water-Soluble Hormones
Chemical Basis	Cholesterol derivatives (steroids); iodinated tyrosine (thyroid hormones)	Modified amino acids (amines) or amino acid chains (peptides, proteins, glycoproteins)
Subtypes	Steroid Hormones, Thyroid Hormones	Amines, Peptides, Proteins, Glycoproteins
Representative Examples	Cortisol, Aldosterone, Testosterone, Estrogen, Thyroxine	Epinephrine, Norepinephrine, Melatonin, Histamine, ADH, Oxytocin, MSH, hGH, Insulin, TSH, FSH, LH

Hypothalamus & Pituitary Axis (Neuroendocrine Control)

Hypothalamus & Pituitary Axis

Neuroendocrine Control · Hypothalamo-Hypophyseal Portal System · Tropic Hormones

2. Hypothalamus & Pituitary Axis (Neuroendocrine Control)

2.1 The Hypothalamus

Located at the base of the diencephalon in the forebrain, the hypothalamus serves as the master neuroendocrine integrator connecting the nervous system to the endocrine system.

Mechanism 1
Neurohormones
Neurons in hypothalamic nuclei synthesize neurohormones that pass along axons to nerve terminals.
Mechanism 2
Hypothalamo-Hypophyseal Portal System
Hypothalamic releasing and inhibiting hormones are delivered to the anterior pituitary via a specialized local vascular capillary network (portal system), bypassing systemic circulation.
Mechanism 3
Direct Neural Control
Hypothalamic neurosecretory cells send axons directly into the posterior pituitary, where ADH and Oxytocin are released into blood capillaries.

Figure: Hypothalamo-Hypophyseal Axis. The hypothalamus controls the anterior pituitary indirectly, via releasing/inhibiting hormones carried through the hypophyseal portal venules, and controls the posterior pituitary directly, via neurosecretory axons running down the infundibulum. The anterior pituitary in turn synthesizes and releases its own tropic and non-tropic hormones, while the posterior pituitary simply stores and releases ADH and Oxytocin that were made in the hypothalamus itself.

2.2 Hypothalamic Hormones Regulating the Anterior Pituitary

Hormone 1
Thyrotropin-Releasing Hormone (TRH)
Tripeptide (3 amino acids). Stimulates release of TSH and Prolactin.
Hormone 2
Gonadotropin-Releasing Hormone (GnRH)
Decapeptide (10 amino acids). Stimulates secretion of FSH and LH.
Hormone 3
Growth Hormone-Releasing Hormone (GHRH)
44 amino acids. Stimulates synthesis and release of Growth Hormone (GH).
Hormone 4
Somatostatin (GHIH)
Growth Hormone-Inhibiting Hormone. Inhibits release of GH and TSH. Synthesized as a precursor (preprosomatostatin) that undergoes proteolytic processing into active forms (Somatostatin-14 and Somatostatin-28).
Hormone 5
Corticotropin-Releasing Hormone (CRH)
41 amino acids. Stimulates secretion of Adrenocorticotropic Hormone (ACTH).
Hormone 6
Prolactin-Inhibiting Hormone (PIH / Dopamine)
Catecholamine amine neurotransmitter. Inhibits release of Prolactin.

Figure: Preprosomatostatin Processing. Somatostatin is not synthesized directly in its active form. The precursor preprosomatostatin first loses its signal peptide to yield prosomatostatin, which is then cleaved at two internal proteolytic sites to yield the two biologically active forms, Somatostatin-14 and Somatostatin-28.

Hypothalamic Hormone	Structure	Action on Anterior Pituitary
TRH	3 amino acids	Stimulates TSH and Prolactin release
GnRH	10 amino acids	Stimulates FSH and LH release
GHRH	44 amino acids	Stimulates GH release
Somatostatin (GHIH)	14 or 28 amino acids	Inhibits GH and TSH release
CRH	41 amino acids	Stimulates ACTH release
PIH (Dopamine)	Catecholamine derivative	Inhibits Prolactin release

2.3 Pituitary Gland (Hypophysis)

Housed in the sella turcica of the sphenoid bone and attached to the hypothalamus via the infundibulum, the pituitary gland is divided into two distinct functional lobes.

1. Anterior Pituitary (Adenohypophysis)

Composed of glandular epithelium. Subdivided into pars distalis and pars intermedia.

Tropic Hormones (regulate other endocrine glands):

TSH (Thyrotropin) — stimulates the thyroid gland to synthesize and release T₃ and T₄.
ACTH (Corticotropin) — 39-amino-acid peptide; stimulates the adrenal cortex to produce glucocorticoids (cortisol).
FSH (Follicle-Stimulating Hormone) — glycoprotein. In females, initiates ovarian follicle development and estrogen secretion. In males, stimulates spermatogenesis in the seminiferous tubules.
LH (Luteinizing Hormone) — glycoprotein. In females, triggers ovulation, formation of the corpus luteum, and secretion of progesterone/estrogen. In males (ICSH), stimulates Leydig cells to produce testosterone.

Non-Tropic Hormones:

GH (Somatotropin) — promotes protein synthesis, amino acid uptake, and tissue growth. Acts indirectly by stimulating the liver to release Insulin-like Growth Factor I (IGF-I / somatomedin C).
Prolactin (PRL) — initiates and maintains milk production (lactation) in mammary glands following priming by estrogen and progesterone.
MSH (Melanocyte-Stimulating Hormone) — secreted by the pars intermedia; stimulates melanin synthesis in cutaneous melanocytes.

2. Posterior Pituitary (Neurohypophysis)

Composed of neural tissue and glial support cells (pituicytes). Does not synthesize hormones; stores and releases neurohormones produced in the supraoptic and paraventricular nuclei of the hypothalamus.

Oxytocin — stimulates smooth muscle contraction of the pregnant uterus during labor, and contraction of myoepithelial cells in mammary glands for milk ejection (the "let-down" reflex).
Vasopressin (Antidiuretic Hormone / ADH) — increases water reabsorption in the distal convoluted tubules and collecting ducts of the kidneys by inserting aquaporin-2 channels. High concentrations cause systemic arteriolar vasoconstriction, elevating blood pressure.

Pineal Gland, Thyroid Gland, and Parathyroid Glands

Pineal, Thyroid & Parathyroid Glands

Melatonin · Thyroid Hormone Synthesis · Calcium Homeostasis

3. Pineal Gland, Thyroid Gland, and Parathyroid Glands

3.1 Pineal Gland (Epiphysis)

A small, pinecone-shaped endocrine gland attached to the roof of the third ventricle in the epithalamus.

Feature 1
Histology
Consists of neuroglia and secretory parenchymal cells called pinealocytes.
Feature 2
Melatonin Synthesis
Synthesized from serotonin, which itself derives from the amino acid tryptophan.
Feature 3
Circadian Rhythm
Light signals received by the retina travel via the retinohypothalamic tract to the suprachiasmatic nucleus (SCN) and superior cervical ganglion, inhibiting melatonin release. Darkness removes this inhibition, increasing melatonin secretion up to 10-fold to promote sleepiness and set biological clocks.

3.2 Thyroid Gland

Located inferior to the larynx, anterior to the trachea. Consists of right and left lateral lobes connected by a median tissue mass called the isthmus.

Histology & Functional Units

Figure: Histology of the Thyroid Gland. Each thyroid follicle is a hollow sphere lined by simple cuboidal follicular epithelium and filled with proteinaceous colloid (thyroglobulin bound to iodinated tyrosine residues). Clusters of parafollicular C-cells sit in the connective tissue between follicles, outside the follicular wall, secreting calcitonin independently of the T₃/T₄ pathway.

Thyroid Follicles
Spherical hollow sacs lined by simple cuboidal epithelial cells (follicular cells).
Colloid
Proteinaceous fluid filling the follicle lumen, consisting primarily of thyroglobulin (a large precursor glycoprotein).
Parafollicular Cells (C-Cells)
Nestled in connective tissue between follicles; secrete calcitonin.

Biosynthesis and Secretion of Thyroid Hormones (T₃ & T₄)

Figure: Thyroid Hormone Biosynthesis Cascade. Iodide is trapped from blood, thyroglobulin is synthesized and secreted into the colloid, iodide is oxidized and attached to tyrosine residues on thyroglobulin, and adjacent iodotyrosines couple to form T₃ and T₄ while still bound to thyroglobulin. Only upon TSH stimulation is colloid reclaimed by pinocytosis and proteolyzed to release free hormone into the bloodstream.

Transport and Mechanism of Action

Property 1
Transport
Over 99% of circulating T₃ and T₄ are bound to plasma carrier proteins, primarily thyroxine-binding globulin (TBG).
Property 2
Peripheral Conversion
Free T₄ enters target cells and is converted into active T₃ by deiodinase enzymes.
Property 3
Nuclear Receptors
T₃ binds to nuclear receptors that act as transcription factors to modulate gene expression.
Property 4
Physiological Effects
Broad downstream actions on metabolism, electrolyte transport, and growth:
- Basal Metabolic Rate (BMR): Increases O₂ consumption and BMR across body tissues (calorigenic effect).
- Electrolyte Transport: Stimulates synthesis of Na⁺/K⁺ ATPase pumps.
- Growth & Development: Essential for normal CNS maturation and skeletal growth in children.

Calcitonin

Trigger
Stimulus
Secreted by parafollicular C-cells in response to hypercalcemia (elevated blood Ca²⁺).
Response
Action
Inhibits osteoclast activity and enhances calcium deposition into bone matrix, lowering plasma Ca²⁺ levels.

3.3 Parathyroid Glands

Four small masses of glandular tissue partially embedded in the posterior surface of the thyroid lobes.

Figure: Calcium Homeostasis Feedback Loop. Rising blood Ca²⁺ triggers thyroid C-cells to release calcitonin, which inhibits osteoclasts and promotes bone deposition, lowering Ca²⁺ back toward normal. Falling blood Ca²⁺ triggers the parathyroid glands to release PTH, which stimulates osteoclasts and increases renal and intestinal Ca²⁺ reabsorption (via calcitriol), raising Ca²⁺ back toward normal — two opposing hormones holding plasma calcium within a narrow homeostatic range.

Regulatory Role
Parathyroid Hormone (PTH / Collip's Hormone)
Major regulator of plasma Ca²⁺, Mg²⁺, and HPO₄²⁻ levels.
Trigger
Stimulus
Released in response to hypocalcemia (low blood Ca²⁺).

Target Organ Actions of PTH

Bone — stimulates osteoclasts to resorb bone matrix, releasing Ca²⁺ and phosphate into the blood.
Kidney — enhances reabsorption of Ca²⁺ while promoting excretion of phosphate in urine.
Intestine — stimulates renal conversion of Vitamin D into active Calcitriol (1,25-dihydroxyvitamin D₃), which increases dietary Ca²⁺ absorption in the GI tract.

Pancreas & Blood Glucose Homeostasis

Islets of Langerhans · Insulin & Glucagon · GLUT-4 Translocation

4. Pancreas & Blood Glucose Homeostasis

4.1 Dual Glandular Architecture

The pancreas is a composite gland situated posterior to the stomach.

98–99%
Exocrine Pancreas
Arranged in clusters called acini that produce digestive enzymes transported via the pancreatic duct to the duodenum.
1–2%
Endocrine Pancreas
Microscopic, vascularized clusters called Islets of Langerhans embedded between the acini.

Figure: Histology of the Pancreatic Islet of Langerhans. Each islet is a well-vascularized cluster of endocrine cells suspended within a sea of exocrine acinar tissue. Beta cells dominate the islet population and secrete insulin; alpha cells secrete the counter-regulatory hormone glucagon; delta cells secrete somatostatin, which paracrine-inhibits both insulin and glucagon release; and F/PP cells secrete pancreatic polypeptide.

4.2 Islet Cell Types and Secretions

17%
Alpha (α) Cells
Secrete Glucagon.
70%
Beta (β) Cells
Secrete Insulin.
7%
Delta (δ) Cells
Secrete Somatostatin — a paracrine inhibitor of both insulin and glucagon release.
Remainder
F Cells (PP Cells)
Secrete Pancreatic Polypeptide, which inhibits somatostatin release, gallbladder contraction, and pancreatic enzyme secretion.

4.3 Insulin Biosynthesis and Proteolytic Processing

Insulin is synthesized as a single-chain precursor molecule that undergoes two sequential proteolytic cleavages before becoming biologically active.

Figure: Insulin Biosynthesis and Proteolytic Processing. Preproinsulin loses its signal peptide in the rough ER to form proinsulin, in which the B and A chains fold and become linked by disulfide bonds while still connected through the C-peptide. A second cleavage excises the C-peptide, leaving mature insulin as two disulfide-linked chains, with free C-peptide co-secreted as an inactive byproduct.

4.4 Physiological Actions: Insulin vs. Glucagon

Figure: Blood Glucose Homeostatic Regulation. Hyperglycemia triggers beta cells to release insulin, which accelerates cellular glucose uptake, stimulates glycogenesis and protein synthesis, and promotes lipogenesis while blocking gluconeogenesis — lowering glucose back to normal. Hypoglycemia triggers alpha cells to release glucagon, which stimulates glycogenolysis, increases gluconeogenesis, and inhibits glycogen synthesis — raising glucose back to normal. Insulin and glucagon act as a classic antagonistic pair maintaining glucose homeostasis.

Metabolic Process	Glucagon Effect	Insulin Effect
Glycogenolysis (glycogen breakdown)	Increases	Inhibits
Glycogenesis (glycogen synthesis)	Decreases	Increases
Gluconeogenesis (glucose from non-carbs)	Increases	Inhibits
Lipolysis (fat breakdown)	Increases	Inhibits
Lipogenesis (fat storage)	Decreases	Increases
Cellular Glucose Uptake (GLUT-4)	No direct effect	Increases
Overall Blood Glucose Level	Elevates	Lowers

4.5 Mechanism of GLUT-4 Translocation

In skeletal muscle and adipose tissue, glucose entry requires the GLUT-4 transporter.

Figure: Cellular Mechanism of Insulin-Mediated Glucose Uptake. In the absence of insulin, GLUT-4 transporters remain sequestered inside intracellular secretory vesicles and membrane glucose permeability stays low. When insulin binds its transmembrane tyrosine-kinase receptor, an intracellular signal cascade drives the GLUT-4 vesicles to translocate and fuse with the plasma membrane, sharply increasing facilitated glucose diffusion into the cytosol.

Baseline
Absence of Insulin
GLUT-4 transporters are sequestered inside intracellular secretory vesicles; membrane permeability to glucose remains low.
Step 1
Insulin Binding
Insulin binds to its transmembrane receptor (a tyrosine kinase), triggering an intracellular signal transduction cascade.
Step 2
Exocytosis
The signal cascade causes GLUT-4-containing vesicles to translocate and fuse with the plasma membrane.
Step 3
Glucose Influx
Translocated GLUT-4 transporters allow rapid facilitated diffusion of glucose into the cytosol.

Adrenal Glands (Suprarenal Glands)

Adrenal Glands

Cortex & Medulla · Renin-Angiotensin-Aldosterone System · Fight-or-Flight Response

5. Adrenal Glands (Suprarenal Glands)

5.1 Anatomical & Histological Organization

Located superior to each kidney. Anatomically divided into two embryologically and functionally distinct regions.

80–90% of Mass
Adrenal Cortex
Outer region, derived from mesoderm.
Inner Core
Adrenal Medulla
Inner core region, derived from neural crest ectoderm.

Figure: Adrenal Gland Histology & Zonation. Beneath the fibrous capsule, the adrenal cortex forms three concentric zones — the thin outer zona glomerulosa (aldosterone), the thick middle zona fasciculata (cortisol), and the netlike inner zona reticularis (adrenal androgens) — surrounding the centrally located adrenal medulla, whose chromaffin cells secrete the catecholamines epinephrine and norepinephrine.

5.2 Adrenal Cortex Functional Zones

Zona Glomerulosa

Secretes Mineralocorticoids, primarily Aldosterone.
Regulates Na⁺ and K⁺ ion balance, blood volume, and blood pressure via the Renin-Angiotensin-Aldosterone System (RAAS).
Promotes renal reabsorption of Na⁺ and water, and secretion of K⁺ into urine.

Figure: Renin-Angiotensin-Aldosterone System (RAAS). Falling blood volume or pressure triggers renal juxtaglomerular cells to secrete renin, which converts hepatic angiotensinogen into angiotensin I; ACE then converts angiotensin I into angiotensin II. Angiotensin II acts on two fronts simultaneously — direct systemic vasoconstriction, and stimulation of the adrenal cortex to secrete aldosterone, which drives renal Na⁺/H₂O retention — both restoring blood pressure and blood volume toward normal.

Zona Fasciculata

Secretes Glucocorticoids, primarily Cortisol (hydrocortisone). Controlled by hypothalamic CRH and pituitary ACTH.

Functions:

Protein breakdown in muscle to liberate amino acids into blood.
Gluconeogenesis in hepatocytes.
Lipolysis in adipose tissue.
Anti-inflammatory actions (inhibits white blood cell inflammatory responses).
Immunosuppression (depresses immune activity at high concentrations).
Resistance to stress (fasting, trauma, infection).

Zona Reticularis

Secretes Adrenal Androgens, mainly Dehydroepiandrosterone (DHEA).
Converted into potent sex steroids (testosterone/estrogen) in peripheral tissues; contributes to libido and pubic/axillary hair growth.

5.3 Adrenal Medulla

A modified sympathetic ganglion consisting of chromaffin cells that lack axons and release neurohormones directly into capillaries.

Secretion Ratio
Catecholamine Secretion
Secretes ~80% Epinephrine (Adrenaline) and ~20% Norepinephrine (Noradrenaline).
Trigger
Fight-or-Flight Response
Triggered by hypothalamic sympathetic impulses during acute stress, trauma, or exercise.
Response
Physiological Effects
Rapid, body-wide mobilization for acute stress:
- Increases heart rate, cardiac contractility, and systolic blood pressure.
- Dilates airways (bronchodilation) and vascular beds to skeletal muscle and heart.
- Elevates blood glucose levels via liver glycogenolysis and lipolysis.

Gonadal Hormones, Hormone Mechanisms & Endocrine Pathophysiology

Gonadal Hormones & Hormone Mechanisms

Gonads & Other Organs · Second Messenger Cascades · Endocrine Pathophysiology

6. Gonadal Hormones & Non-Endocrine Organ Hormones

6.1 Male Gonads (Testes)

Interstitial Cells
Leydig Cells
Located between seminiferous tubules; secrete Testosterone (androgen) under LH regulation.
- Stimulates male reproductive tract development and descent of the testes.
- Drives spermatogenesis (in conjunction with FSH).
- Promotes secondary male sex characteristics (beard growth, voice deepening, muscle mass growth).
Tubule Support
Sertoli Cells
Secrete Inhibin, which selectively inhibits anterior pituitary FSH secretion.

6.2 Female Gonads (Ovaries)

Follicular Phase
Graafian Follicles
Produce Estrogens (primarily Estradiol) in response to FSH/LH. Drives female secondary sex characteristics and the proliferative phase of the uterine lining.
Post-Ovulation
Corpus Luteum
Secretes Progesterone and estrogens following ovulation to prepare and maintain the endometrium for embryo implantation.
Granulosa Cells
Inhibin
Secreted by granulosa cells to inhibit FSH.
Pregnancy / Labor
Relaxin
Secreted by the corpus luteum and placenta during pregnancy to increase flexibility of the pubic symphysis and dilate the uterine cervix during labor.

6.3 Hormones Secreted by Other Organs

Figure: Non-Endocrine Organ Hormones. Several organs whose primary role is not endocrine nonetheless secrete hormones as a secondary function: the kidneys (renin, EPO), placenta (hCG, HCS), GI tract (gastrin, secretin, CCK, GIP), and heart (ANF/ANP) all release signaling molecules that regulate blood pressure, red blood cell production, pregnancy maintenance, and digestion.

Kidneys
- Renin: Enzymatic hormone triggering the RAAS cascade.
- Erythropoietin (EPO): Glycoprotein that acts on red bone marrow to accelerate erythropoiesis (RBC production) in response to hypoxia.
Placenta
- Human Chorionic Gonadotropin (hCG): Maintains corpus luteum secretion of progesterone during early pregnancy.
- Human Chorionic Somatomammotropin (HCS): Promotes mammary development for lactation.
GI Tract
(Enteroendocrine Cells)
- Gastrin (G cells): Stimulates gastric acid (HCl) secretion and gastric motility.
- Secretin (S cells): Stimulates pancreatic duct cells to release bicarbonate-rich fluid to neutralize stomach acid in the duodenum.
- Cholecystokinin (CCK) (I cells): Triggers pancreatic enzyme secretion and gallbladder contraction.
- Gastric Inhibitory Peptide (GIP) (K cells): Inhibits gastric motility and stimulates insulin release.
Heart
Atrial Natriuretic Factor (ANF / ANP): Secreted by atrial myocytes in response to atrial stretch (high blood volume). Promotes renal excretion of Na⁺ and water (natriuresis/diuresis), causing vasodilation and reducing blood pressure.

7. General Mechanisms of Hormone Action & Second Messenger Cascades

7.1 Mode of Action: Lipid-Soluble Hormones

Lipid-soluble hormones (steroids, thyroid hormones) readily diffuse through the hydrophobic phospholipid bilayer of target cell plasma membranes.

Figure: Lipid-Soluble Hormone Action Mechanism. Because steroid and thyroid hormones are lipid-soluble, they diffuse freely across the plasma membrane and bind intracellular (nuclear) receptors directly. The resulting hormone-receptor complex acts as its own transcription factor, turning target genes on or off and driving synthesis of new proteins that carry out the hormone's effect — a comparatively slow but long-lasting mode of action.

7.2 Mode of Action: Water-Soluble Hormones

Water-soluble hormones (peptides, amines, proteins) cannot penetrate the lipid bilayer. They act as first messengers, binding to cell-surface transmembrane receptors.

Figure: Water-Soluble Hormone Second Messenger Cascade. Because peptide, amine, and protein hormones cannot cross the membrane, they bind a surface receptor that activates a G-protein, which in turn stimulates one of two effector enzymes: adenylyl cyclase (generating cAMP, which activates Protein Kinase A) or phospholipase C (generating IP₃ and DAG, which releases Ca²⁺ from the ER). Both second-messenger pathways ultimately alter the activity of existing cellular proteins — a fast but comparatively short-lived mode of action.

8. Endocrine Pathophysiology & Clinical Disorders

8.1 Pituitary Gland Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Pituitary Dwarfism	Hyposecretion of hGH during childhood	Short stature with proportional skeletal growth
Gigantism	Hypersecretion of hGH during childhood, prior to epiphyseal plate closure	Extreme long bone elongation
Acromegaly	Hypersecretion of hGH during adulthood, after epiphyseal plate closure	Thickening of facial bones, hands, feet, and soft tissue enlargement
Diabetes Insipidus	Inability to produce or respond to ADH	Polyuria (dilute urine) and polydipsia (intense thirst)
— Neurogenic DI	Hyposecretion of ADH due to hypothalamic/pituitary damage	Same as Diabetes Insipidus, above
— Nephrogenic DI	Renal tubules fail to respond to ADH (defective receptors / damaged kidney tissue)	Same as Diabetes Insipidus, above

8.2 Thyroid Gland Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Hypothyroidism	Deficient thyroid hormone secretion	Decreased BMR, cold intolerance, weight gain, lethargy, slow heart rate
— Myxedema	Adult-onset hypothyroidism	Facial subcutaneous edema and puffiness
— Cretinism	Congenital hypothyroidism during infancy	Severe mental retardation and stunted physical dwarfism
Hyperthyroidism	Excessive thyroid hormone secretion	Elevated BMR, heat intolerance, weight loss, nervousness, tachycardia
— Graves’ Disease	Autoimmune TSI antibodies chronically activate TSH receptors	Exophthalmos (protruding eyeballs) and diffuse goiter
Goiter	Chronic TSH overstimulation (iodine deficiency or Graves’ disease)	Pathological enlargement of the thyroid gland

8.3 Pancreatic Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Diabetes Mellitus	Inability to metabolize glucose properly	Hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia
— Type 1 (IDDM)	Autoimmune destruction of pancreatic β-cells; absolute insulin deficiency	Requires exogenous insulin therapy
— Type 2 (NIDDM)	Target cell insulin resistance; down-regulation of insulin receptors	Strongly associated with obesity and metabolic syndrome

8.4 Adrenal Gland Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Cushing’s Syndrome	Hypercortisolism from adrenal tumors or excessive ACTH secretion	Upper body obesity, "moon face," "buffalo hump," hyperglycemia, muscle weakness, impaired wound healing
Addison’s Disease	Autoimmune destruction of the adrenal cortex — glucocorticoid & mineralocorticoid hyposecretion	Hypoglycemia, Na⁺/K⁺ imbalance, hypotension, severe dehydration, skin hyperpigmentation

8.5 Parathyroid Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Hypoparathyroidism	Deficient PTH secretion → hypocalcemia	Neuronal hyperexcitability, spontaneous action potentials, muscle twitches, spasms, tetany
Hyperparathyroidism	Excessive PTH secretion	Osteoclastic bone resorption (osteitis fibrosa cystica), bone softness/fragility, hypercalcemia, renal calculi (kidney stones)

9. Comprehensive Summary Table of Endocrine Glands & Hormones

Endocrine Gland	Hormone	Chemical Class	Major Target Organ(s)	Primary Physiological Action
Hypothalamus	TRH, GnRH, GHRH, CRH	Peptides / Proteins	Anterior Pituitary	Stimulate secretion of anterior pituitary hormones
	Somatostatin (GHIH)	Peptide	Anterior Pituitary	Inhibits GH and TSH secretion
	PIH (Dopamine)	Amine	Anterior Pituitary	Inhibits Prolactin secretion
Anterior Pituitary	TSH	Glycoprotein	Thyroid Gland	Stimulates thyroid hormone (T₃/T₄) synthesis & release
	ACTH	Peptide	Adrenal Cortex	Stimulates glucocorticoid (cortisol) release
	FSH	Glycoprotein	Gonads (Ovaries/Testes)	Follicle maturation / Spermatogenesis
	LH	Glycoprotein	Gonads (Ovaries/Testes)	Triggers ovulation / Testosterone secretion
	GH	Protein	Liver, Bone, Muscle	Stimulates tissue growth & IGF-I production
	Prolactin (PRL)	Protein	Mammary Glands	Initiates & maintains milk production
Posterior Pituitary	Oxytocin	Peptide	Uterus, Mammary Gland	Uterine contraction & milk ejection
Posterior Pituitary	ADH (Vasopressin)	Peptide	Kidneys (Tubules)	Water reabsorption & blood pressure elevation
Thyroid Gland	T₃ & T₄	Iodinated Amine	Most Body Tissues	Elevates BMR, regulates development & calorigenesis
Thyroid Gland	Calcitonin	Peptide	Bone Matrix	Lowers blood Ca²⁺ via osteoclast inhibition
Parathyroid Gland	PTH (Collip’s)	Peptide	Bone, Kidneys, Intestine	Elevates blood Ca²⁺ via osteoclasts & calcitriol
Pancreatic Islets	Insulin	Protein (A & B chains)	Liver, Muscle, Adipose	Lowers blood glucose via GLUT-4 & glycogenesis
Pancreatic Islets	Glucagon	Polypeptide	Liver	Elevates blood glucose via glycogenolysis
Adrenal Cortex	Aldosterone	Steroid	Kidney Tubules	Na⁺/H₂O reabsorption, K⁺ excretion
	Cortisol	Steroid	Liver, Muscle, Adipose	Gluconeogenesis, anti-inflammatory action
	DHEA	Steroid	Peripheral Tissues	Sex steroid precursor, libido development
Adrenal Medulla	Epinephrine / Norepinephrine	Amine (Catecholamine)	Heart, Blood Vessels, Lungs	Fight-or-flight response, elevates heart rate & glucose
Pineal Gland	Melatonin	Amine (Tryptophan deriv.)	Brain (SCN)	Sets circadian sleep-wake cycles
Testes	Testosterone	Steroid	Testes, Male Accessory Organs	Spermatogenesis, secondary male sex traits
Ovaries	Estrogens / Progesterone	Steroid	Uterus, Mammary Glands	Menstrual cycle regulation, endometrial maintenance
Kidneys	Erythropoietin (EPO)	Glycoprotein	Red Bone Marrow	Stimulates red blood cell production
Heart	ANF / ANP	Peptide	Kidneys, Blood Vessels	Promotes Na⁺ excretion, lowers blood pressure

Gonadal Hormones, Hormone Mechanisms & Endocrine Pathophysiology

Gonadal Hormones & Hormone Mechanisms

Gonads & Other Organs · Second Messenger Cascades · Endocrine Pathophysiology

6. Gonadal Hormones & Non-Endocrine Organ Hormones

6.1 Male Gonads (Testes)

Interstitial Cells
Leydig Cells
Located between seminiferous tubules; secrete Testosterone (androgen) under LH regulation.
- Stimulates male reproductive tract development and descent of the testes.
- Drives spermatogenesis (in conjunction with FSH).
- Promotes secondary male sex characteristics (beard growth, voice deepening, muscle mass growth).
Tubule Support
Sertoli Cells
Secrete Inhibin, which selectively inhibits anterior pituitary FSH secretion.

6.2 Female Gonads (Ovaries)

Follicular Phase
Graafian Follicles
Produce Estrogens (primarily Estradiol) in response to FSH/LH. Drives female secondary sex characteristics and the proliferative phase of the uterine lining.
Post-Ovulation
Corpus Luteum
Secretes Progesterone and estrogens following ovulation to prepare and maintain the endometrium for embryo implantation.
Granulosa Cells
Inhibin
Secreted by granulosa cells to inhibit FSH.
Pregnancy / Labor
Relaxin
Secreted by the corpus luteum and placenta during pregnancy to increase flexibility of the pubic symphysis and dilate the uterine cervix during labor.

6.3 Hormones Secreted by Other Organs

Kidneys
- Renin: Enzymatic hormone triggering the RAAS cascade.
- Erythropoietin (EPO): Glycoprotein that acts on red bone marrow to accelerate erythropoiesis (RBC production) in response to hypoxia.
Placenta
- Human Chorionic Gonadotropin (hCG): Maintains corpus luteum secretion of progesterone during early pregnancy.
- Human Chorionic Somatomammotropin (HCS): Promotes mammary development for lactation.
GI Tract
(Enteroendocrine Cells)
- Gastrin (G cells): Stimulates gastric acid (HCl) secretion and gastric motility.
- Secretin (S cells): Stimulates pancreatic duct cells to release bicarbonate-rich fluid to neutralize stomach acid in the duodenum.
- Cholecystokinin (CCK) (I cells): Triggers pancreatic enzyme secretion and gallbladder contraction.
- Gastric Inhibitory Peptide (GIP) (K cells): Inhibits gastric motility and stimulates insulin release.
Heart
Atrial Natriuretic Factor (ANF / ANP): Secreted by atrial myocytes in response to atrial stretch (high blood volume). Promotes renal excretion of Na⁺ and water (natriuresis/diuresis), causing vasodilation and reducing blood pressure.

7. General Mechanisms of Hormone Action & Second Messenger Cascades

7.1 Mode of Action: Lipid-Soluble Hormones

Lipid-soluble hormones (steroids, thyroid hormones) readily diffuse through the hydrophobic phospholipid bilayer of target cell plasma membranes.

7.2 Mode of Action: Water-Soluble Hormones

Water-soluble hormones (peptides, amines, proteins) cannot penetrate the lipid bilayer. They act as first messengers, binding to cell-surface transmembrane receptors.

8. Endocrine Pathophysiology & Clinical Disorders

8.1 Pituitary Gland Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Pituitary Dwarfism	Hyposecretion of hGH during childhood	Short stature with proportional skeletal growth
Gigantism	Hypersecretion of hGH during childhood, prior to epiphyseal plate closure	Extreme long bone elongation
Acromegaly	Hypersecretion of hGH during adulthood, after epiphyseal plate closure	Thickening of facial bones, hands, feet, and soft tissue enlargement
Diabetes Insipidus	Inability to produce or respond to ADH	Polyuria (dilute urine) and polydipsia (intense thirst)
— Neurogenic DI	Hyposecretion of ADH due to hypothalamic/pituitary damage	Same as Diabetes Insipidus, above
— Nephrogenic DI	Renal tubules fail to respond to ADH (defective receptors / damaged kidney tissue)	Same as Diabetes Insipidus, above

8.2 Thyroid Gland Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Hypothyroidism	Deficient thyroid hormone secretion	Decreased BMR, cold intolerance, weight gain, lethargy, slow heart rate
— Myxedema	Adult-onset hypothyroidism	Facial subcutaneous edema and puffiness
— Cretinism	Congenital hypothyroidism during infancy	Severe mental retardation and stunted physical dwarfism
Hyperthyroidism	Excessive thyroid hormone secretion	Elevated BMR, heat intolerance, weight loss, nervousness, tachycardia
— Graves’ Disease	Autoimmune TSI antibodies chronically activate TSH receptors	Exophthalmos (protruding eyeballs) and diffuse goiter
Goiter	Chronic TSH overstimulation (iodine deficiency or Graves’ disease)	Pathological enlargement of the thyroid gland

8.3 Pancreatic Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Diabetes Mellitus	Inability to metabolize glucose properly	Hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia
— Type 1 (IDDM)	Autoimmune destruction of pancreatic β-cells; absolute insulin deficiency	Requires exogenous insulin therapy
— Type 2 (NIDDM)	Target cell insulin resistance; down-regulation of insulin receptors	Strongly associated with obesity and metabolic syndrome

8.4 Adrenal Gland Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Cushing’s Syndrome	Hypercortisolism from adrenal tumors or excessive ACTH secretion	Upper body obesity, "moon face," "buffalo hump," hyperglycemia, muscle weakness, impaired wound healing
Addison’s Disease	Autoimmune destruction of the adrenal cortex — glucocorticoid & mineralocorticoid hyposecretion	Hypoglycemia, Na⁺/K⁺ imbalance, hypotension, severe dehydration, skin hyperpigmentation

8.5 Parathyroid Disorders

Disorder	Cause / Mechanism	Key Signs & Symptoms
Hypoparathyroidism	Deficient PTH secretion → hypocalcemia	Neuronal hyperexcitability, spontaneous action potentials, muscle twitches, spasms, tetany
Hyperparathyroidism	Excessive PTH secretion	Osteoclastic bone resorption (osteitis fibrosa cystica), bone softness/fragility, hypercalcemia, renal calculi (kidney stones)

9. Comprehensive Summary Table of Endocrine Glands & Hormones

Endocrine Gland	Hormone	Chemical Class	Major Target Organ(s)	Primary Physiological Action
Hypothalamus	TRH, GnRH, GHRH, CRH	Peptides / Proteins	Anterior Pituitary	Stimulate secretion of anterior pituitary hormones
	Somatostatin (GHIH)	Peptide	Anterior Pituitary	Inhibits GH and TSH secretion
	PIH (Dopamine)	Amine	Anterior Pituitary	Inhibits Prolactin secretion
Anterior Pituitary	TSH	Glycoprotein	Thyroid Gland	Stimulates thyroid hormone (T₃/T₄) synthesis & release
	ACTH	Peptide	Adrenal Cortex	Stimulates glucocorticoid (cortisol) release
	FSH	Glycoprotein	Gonads (Ovaries/Testes)	Follicle maturation / Spermatogenesis
	LH	Glycoprotein	Gonads (Ovaries/Testes)	Triggers ovulation / Testosterone secretion
	GH	Protein	Liver, Bone, Muscle	Stimulates tissue growth & IGF-I production
	Prolactin (PRL)	Protein	Mammary Glands	Initiates & maintains milk production
Posterior Pituitary	Oxytocin	Peptide	Uterus, Mammary Gland	Uterine contraction & milk ejection
Posterior Pituitary	ADH (Vasopressin)	Peptide	Kidneys (Tubules)	Water reabsorption & blood pressure elevation
Thyroid Gland	T₃ & T₄	Iodinated Amine	Most Body Tissues	Elevates BMR, regulates development & calorigenesis
Thyroid Gland	Calcitonin	Peptide	Bone Matrix	Lowers blood Ca²⁺ via osteoclast inhibition
Parathyroid Gland	PTH (Collip’s)	Peptide	Bone, Kidneys, Intestine	Elevates blood Ca²⁺ via osteoclasts & calcitriol
Pancreatic Islets	Insulin	Protein (A & B chains)	Liver, Muscle, Adipose	Lowers blood glucose via GLUT-4 & glycogenesis
Pancreatic Islets	Glucagon	Polypeptide	Liver	Elevates blood glucose via glycogenolysis
Adrenal Cortex	Aldosterone	Steroid	Kidney Tubules	Na⁺/H₂O reabsorption, K⁺ excretion
	Cortisol	Steroid	Liver, Muscle, Adipose	Gluconeogenesis, anti-inflammatory action
	DHEA	Steroid	Peripheral Tissues	Sex steroid precursor, libido development
Adrenal Medulla	Epinephrine / Norepinephrine	Amine (Catecholamine)	Heart, Blood Vessels, Lungs	Fight-or-flight response, elevates heart rate & glucose
Pineal Gland	Melatonin	Amine (Tryptophan deriv.)	Brain (SCN)	Sets circadian sleep-wake cycles
Testes	Testosterone	Steroid	Testes, Male Accessory Organs	Spermatogenesis, secondary male sex traits
Ovaries	Estrogens / Progesterone	Steroid	Uterus, Mammary Glands	Menstrual cycle regulation, endometrial maintenance
Kidneys	Erythropoietin (EPO)	Glycoprotein	Red Bone Marrow	Stimulates red blood cell production
Heart	ANF / ANP	Peptide	Kidneys, Blood Vessels	Promotes Na⁺ excretion, lowers blood pressure

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Human Physiology: Endocrine System

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