The Endocrine System - Lecture Notes

The Endocrine System — Comprehensive Notes

Lecture 9, Pre-Matriculation | Mark W. Burke, PhD

1. Introduction
The endocrine and nervous systems function together to regulate body activities
The endocrine system releases hormones to control body activities and maintain homeostasis
Compared to the nervous system’s rapid communication, endocrine responses are slower and more sustained

What the Endocrine System Controls/Integrates

Reproduction
Growth and development
Maintenance of electrolyte, water, and nutrient balance of blood
Regulation of cellular metabolism and energy balance
Mobilization of body defenses

Exocrine vs. Endocrine Glands

Feature Exocrine Endocrine

Secretion Nonhormonal substances (sweat, saliva) Hormones

Ducts Have ducts to carry secretion to a membrane Lack ducts; secrete into interstitial fluid →
surface diffuse into blood

A hormone = a molecule released in one part of the body that regulates activity of cells elsewhere
The endocrine system = all endocrine glands + hormone-secreting cells

Endocrine Organs Overview

Primary endocrine glands: pituitary, thyroid, parathyroid, adrenal, pineal
Hypothalamus — a neuroendocrine organ
Mixed exocrine/endocrine organs: pancreas, gonads, placenta
Other hormone-producing tissues: adipose cells, thymus, cells in walls of small intestine, stomach, kidneys, heart

2. Chemical Messengers
Hormones — long-distance chemical signals; travel via blood or lymph
Autocrines — chemicals that act on the same cells that secreted them
Paracrines — locally acting chemicals that affect nearby cells (not the secreting cell)
Autocrines and paracrines are local chemical messengers and are not considered part of the classic endocrine system

Role of Hormone Receptors

Hormones affect only target cells with specific receptors for that hormone
Receptor numbers can change:
Down-regulation — decreased receptor number when hormone is in excess → target tissue becomes less sensitive
Up-regulation — increased receptor number when hormone is deficient → target tissue becomes more sensitive

3. Chemical Classes of Hormones

Two Main Classes

Amino acid-based hormones — amino acid derivatives, peptides, proteins
 Steroids — synthesized from cholesterol; gonadal and adrenocortical hormones

By Solubility

Lipid-soluble Water-soluble

Steroid hormones Amine hormones

Thyroid hormones Peptide hormones

Nitric oxide gas Protein hormones

Eicosanoid hormones (though generally considered lipid-soluble in

practice)

Water-soluble hormones (all amino acid-based hormones except thyroid hormone):

Act on plasma membrane receptors via G protein second messengers
Cannot enter the cell

Lipid-soluble hormones (steroid and thyroid hormones):

Act on intracellular receptors that directly activate genes
Can enter the cell

Note: although sometimes tabled as water-soluble, eicosanoids/prostaglandins are generally lipid-soluble

Preprohormone → Prohormone → Hormone

Preprohormone — large, inactive precursor
Prohormone — smaller, still inactive; created via proteolytic post-translational modification
Peptide/protein hormones bind surface membrane receptors and act through a signal transduction system

4. Hormone Transport in Blood

Lipid-soluble hormones — mostly circulate attached to a transport protein (<10% free fraction)
Transport proteins are synthesized in the liver
Functions: increase blood solubility, prevent loss of small hormone molecules to urine, provide a ready hormone
reserve

Water-soluble hormones — circulate unattached (free) in blood plasma

5. Mechanism of Hormone Action

Target Cell Responses

Synthesis of new molecules
Alteration of cell membrane permeability
Stimulation of membrane transport
Alteration of metabolic rate
Contraction of smooth or cardiac muscle

General Mechanisms
Lipid-soluble hormones — bind receptors within target cells
Water-soluble hormones — bind receptors on the outside of the cell membrane, initiating an intracellular chain
reaction

6. Plasma Membrane Receptors and Second-Messenger Systems

cAMP Signaling Mechanism

1. Hormone (first messenger) binds to its receptor
2. Receptor activates a G protein
3. G protein activates adenylate cyclase
4. Adenylate cyclase converts ATP → cAMP (second messenger)
5. cAMP activates protein kinases that phosphorylate proteins → activating some, inactivating others
6. cAMP is rapidly degraded by phosphodiesterase
7. Intracellular enzymatic cascades produce a huge amplification effect

PIP2–Calcium Signaling Mechanism

Involves a G protein and membrane-bound effector phospholipase C
Phospholipase C splits PIP2 into two second messengers:
Diacylglycerol (DAG) — activates protein kinase
Inositol trisphosphate (IP3) — causes Ca2+ release

Ca2+ acts as a second messenger:

Alters enzyme activity and ion channels
Binds regulatory protein calmodulin
Calcium-bound calmodulin activates enzymes that amplify the cellular response

Peptide Hormone–Receptor Complex

Peptide hormones (H) cannot enter target cells; they must bind membrane receptors (R) that initiate signal
transduction
Key proteins involved: TK (tyrosine kinase), AE (amplifier enzyme), G (G protein)
Signal transduction can: open an ion channel, or trigger second-messenger systems that phosphorylate proteins →
cellular response

Other Signaling Mechanisms

cGMP — second messenger for some hormones
Some hormones act without a second messenger:
E.g., the insulin receptor is itself a tyrosine kinase enzyme that autophosphorylates upon insulin binding, creating
docking sites for relay proteins that trigger cell responses

7. Intracellular Receptors and Direct Gene Activation

Applies to steroid hormones and thyroid hormone

1. Hormone diffuses into the target cell and binds an intracellular receptor
2. The receptor–hormone complex enters the nucleus and binds a specific region of DNA
3. Prompts DNA transcription to produce mRNA
4. mRNA directs protein synthesis
5. Promotes metabolic activities, or synthesis of structural/export proteins

Steroid Hormone Properties

Cholesterol-derived; lipophilic, cross membranes easily
Bind carrier proteins in blood; longer half-life
Act via cytoplasmic/nuclear receptors → genomic effects (activate/repress genes) — slower acting
Can also act via cell membrane receptors → nongenomic responses (faster)

8. Control of Hormone Action and Secretion

Target Cell Responsiveness Depends On:

Hormone’s concentration
Abundance of target cell receptors
Influences of other hormones (permissive, synergistic, antagonistic)

Control of Hormone Secretion

 Signals from the nervous system
Chemical changes in the blood
Other hormones

Target Cell Specificity

Target cells must have specific receptors — e.g.:
ACTH receptors — found only on certain adrenal cortex cells
Thyroxine receptors — found on nearly all cells of the body

Target Cell Activation Depends On 3 Factors

1. Blood levels of hormone
2. Relative number of receptors on/in the target cell
3. Affinity of binding between receptor and hormone

9. Interaction of Hormones at Target Cells

Permissiveness — one hormone cannot exert its effects without another hormone present
Cortisol has a permissive effect on growth hormone
Thyroid hormone permissively supports reproductive regulation (stimulates hepatic synthesis of sex steroid-binding
globulin)
Estrogen stimulates initial endometrial thickening; progesterone then increases thickness — without estrogen, the
progesterone response is weak

Synergism — more than one hormone produces the same effect on a target → amplification
Milk production/secretion requires synergistic action of estrogen, cortisol, prolactin, oxytocin, and others
Testosterone + FSH required for normal sperm production
Thyroid hormone increases the number of epinephrine receptors at target cells, amplifying epinephrine’s effect

Antagonism — one or more hormones oppose the action of another

Glucagon opposes insulin

10. Control of Hormone Release

Blood hormone levels are controlled by negative feedback systems, varying only within a narrow, desirable range
Endocrine glands are stimulated to secrete hormones in response to 3 types of stimuli:

1. Humoral Stimulus
Changing blood levels of ions/nutrients directly stimulate hormone secretion
Example: declining blood Ca2+ stimulates parathyroid glands to secrete PTH → PTH raises blood Ca2+ → stimulus
removed

2. Neural Stimulus
Nerve fibers stimulate hormone release
Example: sympathetic fibers stimulate the adrenal medulla to secrete catecholamines (epinephrine/norepinephrine)

3. Hormonal Stimulus
Hormones stimulate other endocrine organs to release their hormones
Example: hypothalamic hormones stimulate release of most anterior pituitary hormones; anterior pituitary hormones
stimulate other glands to secrete more hormones
Hypothalamic-pituitary-target organ feedback loop — hormones from final target organs inhibit anterior pituitary
hormone release

11. Hypothalamus and Pituitary Gland — Overview

The hypothalamus is the major integrating link between the nervous and endocrine systems
 Region of the brain below the thalamus; contains cell bodies of neurosecretory cells
The pituitary gland controls other endocrine glands, but is itself controlled by the hypothalamus
Some hypothalamic hormones stimulate/inhibit anterior pituitary hormone release
Others are stored and released from the posterior pituitary

Pituitary Gland (Hypophysis) — Anatomy

Connected to the hypothalamus by the infundibulum
Sits in the sella turcica of the sphenoid bone
Two lobes:
Anterior pituitary (adenohypophysis) — glandular tissue
Posterior pituitary — neural tissue (axon terminals of neurosecretory cells)

12. Hypothalamus/Anterior Pituitary Relationship

Hypophyseal portal system — a portal vein links the hypothalamus and anterior pituitary
Hormones carried from a primary capillary plexus to a secondary capillary plexus
Anterior pituitary hormones then enter general circulation from the secondary plexus to reach target cells

Tropic hormones (tropins) — influence the secretion of another endocrine gland

Anterior Lobe Development & Vasculature

Originates as an out-pocketing of oral mucosa (embryologically epithelial in origin)
Vascular (not neural) connection to the hypothalamus via the hypophyseal portal system:
Primary capillary plexus → hypophyseal portal veins → secondary capillary plexus
Carries releasing and inhibiting hormones to regulate anterior pituitary hormone secretion

Control of Anterior Pituitary Secretion

Releasing hormones from the hypothalamus — stimulate anterior pituitary hormone secretion
Inhibiting hormones from the hypothalamus — suppress anterior pituitary hormone secretion
Negative feedback — from rising blood levels of hormones released by target glands

13. Anterior Pituitary Hormones — Overview

Seven major hormones:
1. Adrenocorticotropic hormone (ACTH)
2. Human growth hormone (hGH)
3. Thyroid-stimulating hormone (TSH)
4. Follicle-stimulating hormone (FSH)
5. Luteinizing hormone (LH)
6. Prolactin (PRL)
7. Melanocyte-stimulating hormone (MSH)

All are proteins

All except GH activate the cyclic AMP second-messenger system at their targets
TSH, ACTH, FSH, LH are all tropic hormones (regulate secretory action of other endocrine glands)

14. Adrenocorticotropic Hormone (ACTH)

Secreted by corticotropic cells of the anterior pituitary
Controls secretion of glucocorticoids (e.g., cortisol) from the adrenal cortex
Secretion stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus, in a daily rhythm
Also stimulated by stress-related stimuli (fever, hypoglycemia, other stressors)
Negative feedback: rising cortisol levels inhibit both ACTH and CRH release
Cortisol Is Essential for Life
Helps the body cope with long-term stress; protects against hypoglycemia by stimulating catabolism of energy stores
Major effects:
Promotes gluconeogenesis
Causes breakdown of skeletal muscle proteins
Enhances lipolysis
Suppresses the immune system
Causes negative calcium balance
Influences brain function

Blood cortisol concentration follows a diurnal rhythm (varies throughout the day)

Cortisol as a Therapeutic Drug

Suppresses the immune system; inhibits inflammatory response
Uses: bee stings, poison ivy, pollen allergies; prevents transplant rejection
Long-term use can inhibit ACTH secretion and cause atrophy of cortisol-secreting cells

Hypercortisolism (Cushing’s Syndrome)

Causes:
Adrenal tumor autonomously secreting cortisol
Pituitary tumor autonomously secreting ACTH (Cushing’s disease)
Iatrogenic hypercortisolism (from long-term corticosteroid therapy)

Signs: “buffalo hump” of fat on the upper back, other characteristic changes in body composition

Hypocortisolism
Hyposecretion is much less common than hypersecretion
Addison’s disease — hyposecretion of all adrenal steroid hormones, due to autoimmune destruction of the adrenal
cortex
Tuberculosis accounts for ~20% of cases; the rest are autoimmune
Symptoms: fatigue, dizziness, muscle weakness, weight loss, difficulty standing, nausea, sweating, mood/personality
changes

15. Human Growth Hormone (hGH)

Produced by somatotropic cells
Promotes synthesis/secretion of insulin-like growth factors (IGFs) that stimulate body growth and repair, increase
lipolysis, and elevate blood glucose

Direct (Metabolic) Actions

Increases blood fatty acid levels; encourages fatty acid use for fuel; promotes protein synthesis
Decreases glucose uptake/metabolism (conserves glucose) — an anti-insulin effect
Promotes glycogen breakdown and glucose release to blood

Indirect (Growth-Promoting) Actions

Mediated via IGFs, which stimulate:
Nutrient uptake for DNA and protein synthesis
Collagen formation and bone matrix deposition
Major targets: bone and skeletal muscle

Regulation

GHRH (growth hormone-releasing hormone) — stimulates release

GHIH/somatostatin (growth hormone-inhibiting hormone) — inhibits release
Ghrelin (hunger hormone) — also stimulates release
Blood glucose level is a major regulator of GHRH/GHIH secretion
Growth Requires 4 Factors
1. Growth hormone (and several other hormones)
2. Adequate diet
3. Absence of chronic stress
4. Genetic potential for growth

Homeostatic Imbalances of GH

Hypersecretion:
In children → gigantism
In adults → acromegaly (lengthening of jaw, coarsening of features, growth of hands/feet — since growth plates are
already closed)

Hyposecretion:
In children → pituitary dwarfism

Genetically engineered human GH is available clinically

16. Thyroid-Stimulating Hormone (TSH)

Produced by thyrotropic cells of the anterior pituitary
Stimulates the thyroid gland to secrete T3 (triiodothyronine) and T4 (thyroxine)
Secretion stimulated by TRH (thyrotropin-releasing hormone) from the hypothalamus
Negative feedback: rising T3/T4 blood levels inhibit TRH and TSH release

17. Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)

Both secreted by gonadotrophs of the anterior pituitary
Absent from blood in prepubertal children
Release triggered by GnRH (gonadotropin-releasing hormone) during/after puberty
Suppressed by gonadal hormone feedback

FSH

Females: targets ovaries — stimulates monthly development of several ovarian follicles surrounding a developing
oocyte (gamete production)
Males: targets testes — stimulates sperm production

LH

Females: triggers ovulation; stimulates progesterone secretion by the ovary post-ovulation; with FSH, stimulates
estrogen secretion
Males: stimulates testosterone secretion by the testes
LH promotes production of gonadal hormones generally

18. Prolactin (PRL)

Secreted by prolactin cells of the anterior pituitary
Initiates milk production by mammary glands
Regulation: primarily controlled by PIH (prolactin-inhibiting hormone) = dopamine
Blood levels rise toward the end of pregnancy
Suckling reduces PIH → increases PRL secretion → promotes continued milk production

Role in males not well understood; hypersecretion causes inappropriate lactation, amenorrhea, infertility in females,
and erectile dysfunction/impotence in males

19. Melanocyte-Stimulating Hormone (MSH)

 Function in humans is unknown, but brain receptors suggest possible influence on brain activity
Secretion stimulated by excess CRH; inhibited by PIH
Excess can cause skin darkening

20. Hypothalamus/Posterior Pituitary

The posterior pituitary does not synthesize any hormones itself
It stores and releases hormones made by hypothalamic neurosecretory cell axons
Release is triggered by nerve impulses
Posterior pituitary hormones: oxytocin, antidiuretic hormone (ADH)

Anatomy & Cell Origin

Posterior pituitary = downgrowth of hypothalamic neural tissue
Neural connection to hypothalamus via the hypothalamic-hypophyseal tract
Hypothalamic nuclei (supraoptic and paraventricular nuclei) synthesize oxytocin and ADH
Cell bodies are large neurons (“magnocellular neurons”) located in the hypothalamus, not the pituitary itself
Neurohormones are transported down axons and stored in the posterior pituitary until release

Release Sequence
1. Hypothalamic neurons synthesize oxytocin or ADH
2. Hormones transported down axons of the hypothalamic-hypophyseal tract to the posterior pituitary
3. Stored in axon terminals in the posterior pituitary
4. When hypothalamic neurons fire, action potentials trigger hormone release into the blood

21. Oxytocin (OT)

Enhances smooth muscle contraction in the uterine wall to facilitate labor/delivery
Stimulates milk ejection (“let-down”) from mammary glands after delivery
Secretion stimulated by uterine stretching and suckling during nursing
Function in males/nonpregnant females unclear, but may foster parental caretaking behavior and sexual pleasure
Also acts as a neurotransmitter in the brain

22. Antidiuretic Hormone (ADH / Vasopressin)

Causes kidneys to return more water to the blood (decreases urine volume)
Decreases water loss through sweat glands
Causes arteriolar constriction → increases blood pressure (hence “vasopressin”)
Secretion stimulated by high blood osmotic pressure; inhibited by low osmotic pressure
Release also triggered by pain, low blood pressure, certain drugs
Inhibited by alcohol and diuretics (explains frequent urination with alcohol consumption)
High concentrations cause vasoconstriction

ADH-Related Disorders
Diabetes insipidus — ADH deficiency due to hypothalamus/posterior pituitary damage; patient must stay well-hydrated
SIADH (Syndrome of Inappropriate ADH secretion) — excess ADH → fluid retention, headache, disorientation;
treated with fluid restriction and blood sodium monitoring

23. Thyroid Gland

Anatomy
Located inferior to the larynx, anterior to the trachea
 Thyroid follicles with follicular cells produce T3 and T4
Parafollicular (C) cells produce calcitonin (CT)
The only endocrine gland that stores its secretory products in large supply
Two lateral lobes connected by the isthmus
Follicles produce the glycoprotein thyroglobulin; colloid (thyroglobulin + iodine) fills the follicle lumen as the
precursor of thyroid hormone

T3 and T4
T4 (thyroxine) — 2 tyrosines + 4 bound iodine atoms
T3 (triiodothyronine) — 2 tyrosines + 3 bound iodine atoms
Synthesized from iodine and tyrosine within thyroglobulin
Transported in blood bound to thyroxine-binding globulin (TBG)
Secretion controlled by TRH (hypothalamus) and TSH (anterior pituitary)
Affects virtually every cell in the body

Thyroid Hormone Synthesis (Sequence)

1. Thyroglobulin synthesized and discharged into the follicle lumen
2. Iodide (I⁻) actively transported into the follicular cell
3. Iodide oxidized to iodine
4. Iodine attached to tyrosine in colloid → forms MIT (monoiodotyrosine) and DIT (diiodotyrosine)
5. Iodinated tyrosines linked together → T3 (MIT+DIT) and T4 (DIT+DIT)
6. Thyroglobulin colloid is endocytosed and combined with a lysosome
7. Lysosomal enzymes cleave T3/T4 from thyroglobulin; hormones diffuse into the bloodstream

Thyroid Gland Control

T3 and T4 transported by TBGs
T3 is ~10x more biologically active than T4; peripheral tissues convert T4 → T3
Negative feedback: rising TH levels inhibit TSH release
Hypothalamic TRH can override negative feedback during pregnancy or cold exposure

Hyperthyroidism (Chronic High TH)

Increases O2 consumption and metabolic heat production
Increases protein catabolism → may cause muscle weakness
Hyperexcitable reflexes, psychological disturbances
Influences beta-adrenergic receptors in the heart → high heart rate and force of contraction
Graves’ disease — thyroid-stimulating immunoglobulins (TSI) mimic TSH, binding TSH receptors and causing gland
hypertrophy
Exophthalmos — bulging eyeball from excessive mucopolysaccharide deposition in the bony orbit; sign of
hyperthyroidism

Hypothyroidism (Chronic Low TH)

Slowed metabolic rate and O2 consumption
Decreased protein synthesis
Nervous system effects: slowed reflexes, slow speech/thought, fatigue
Cretinism (congenital hypothyroidism) in infants
Bradycardia (slow heart rate)
Myxedema — mucopolysaccharide deposits beneath the skin causing bags under the eyes (adult hypothyroidism)

Goiter

Hypertrophy of the thyroid gland due to excessive TSH stimulation

Occurs in both hypothyroidism (lack of negative feedback → high TSH) and hyperthyroidism (TSI antibodies mimic TSH)
Iodine-deficiency goiter is a classic hypothyroid cause

24. Calcitonin (CT)

 Produced by parafollicular (C) cells
Lowers blood calcium and phosphate levels
Promotes calcium uptake into bone extracellular matrix
Secretion stimulated by high blood calcium
Functions as an antagonist to PTH
No major known physiological role in normal human adults, but at pharmacologic doses: inhibits osteoclast activity and
stimulates Ca2+ incorporation into bone

25. Parathyroid Gland and Hormone

Anatomy
Embedded in the posterior surface of the thyroid gland (4–8 tiny glands)
Chief (parathyroid) cells — produce PTH
Oxyphil cells — function unknown

Parathyroid Hormone (PTH)

The most important hormone in calcium homeostasis

Regulates blood Ca2+, Mg2+, and phosphate (HPO4²⁻)
Effects:
Increases Ca2+ and HPO4²⁻ release from bone to blood (stimulates osteoclasts)
Decreases Ca2+/Mg2+ loss from blood to urine (enhances renal reabsorption)
Increases HPO4²⁻ loss from blood to urine (phosphate excretion)
Stimulates renal synthesis of calcitriol (activated vitamin D) → increases intestinal absorption of Ca2+, HPO4²⁻,
Mg2+

Secretion stimulated by low blood Ca2+ (opposite trigger to calcitonin); negative feedback as Ca2+ rises

Homeostatic Imbalances

Hyperparathyroidism (often due to tumor) — bones soften/deform; elevated Ca2+ depresses the nervous system and
contributes to kidney stones
Hypoparathyroidism (gland trauma/removal, dietary Mg deficiency) — results in tetany, respiratory paralysis, death

26. Adrenal Gland

Anatomy
Located superior to each kidney; two structurally/functionally distinct regions:
Adrenal cortex — three zones, produces steroid hormones
Outer zone (zona glomerulosa) — mineralocorticoids
Middle zone (zona fasciculata) — glucocorticoids
Inner zone (zona reticularis) — androgens (gonadocorticoids)

Adrenal medulla — modified sympathetic ganglion; secretes epinephrine and norepinephrine

27. Aldosterone (Major Mineralocorticoid)

Increases kidney reabsorption of Na+ and water (blood ← urine)
Increases excretion of K+ into urine
Helps regulate blood pressure and volume
Regulates Na+ (ECF volume, blood volume/pressure, other ion levels) and K+ (sets resting membrane potential)

Control of Aldosterone Secretion

1. Renin-angiotensin-aldosterone mechanism — decreased blood pressure → kidneys release renin → triggers

angiotensin II formation → potent stimulator of aldosterone
2. Plasma K+ concentration — increased K+ directly stimulates zona glomerulosa cells to release aldosterone
3. ACTH — causes small increases in aldosterone during stress
4. Atrial natriuretic peptide (ANP) — blocks renin and aldosterone secretion → decreases blood pressure

Aldosteronism
Hypersecretion, often due to adrenal tumors
Causes hypertension and edema (excess Na+); K+ excretion leads to abnormal neuron/muscle function

28. Glucocorticoids
Keep blood glucose relatively constant
Maintain blood pressure by increasing vasoconstrictor action
Cortisol (hydrocortisone) — the only glucocorticoid present in significant amounts in humans (also: cortisone,
corticosterone)

Cortisol — Detailed Effects

Released in response to ACTH, eating/activity patterns, and stress
Prime effect: gluconeogenesis (glucose formation from fats/proteins)
Promotes rises in blood glucose, fatty acids, amino acids — “saves” glucose for the brain
Enhances vasoconstriction → raises blood pressure for rapid nutrient distribution
Increases protein breakdown; breaks down triglycerides; inhibits inflammation/immune response
Controlled by CRH (hypothalamus) and ACTH (anterior pituitary)

Homeostatic Imbalances of Glucocorticoids

Hypersecretion — Cushing’s syndrome/disease:
Depresses cartilage/bone formation
Inhibits inflammation, depresses immune system
Disrupts cardiovascular, neural, GI function

Hyposecretion — Addison’s disease:

Also involves mineralocorticoid deficits
Decreased glucose and Na+ levels
Weight loss, severe dehydration, hypotension

29. Adrenal Androgens (Gonadocorticoids)

Produced in both sexes; more significant effect in females (since gonads dominate androgen production in males)
Stimulate axillary/pubic hair growth, aid prepubertal growth spurts, contribute to libido in females
Regulation not fully understood, but influenced by ACTH
In postmenopausal women, adrenal androgens are converted to estrogens

Hypersecretion — Adrenogenital Syndrome (Masculinization)

Not very noticeable in adult males
Prepubertal boys — reproductive organs mature and secondary sex characteristics emerge early
Females — beard growth, masculine body hair pattern, clitoral enlargement resembling a small penis

30. Adrenal Medulla

Chromaffin cells synthesize epinephrine (~80%) and norepinephrine (~20%)
Effects: vasoconstriction, increased heart rate, increased blood glucose, blood diverted to brain/heart/skeletal muscle

Epinephrine and Norepinephrine — Detail

Augment the sympathetic “fight-or-flight” response
Increase heart rate and contraction force
 Increase blood flow to heart, liver, skeletal muscle, adipose tissue
Dilate airways
Increase blood glucose and fatty acid levels
Secretion controlled directly by the autonomic nervous system during stress/exercise
Responses are brief
Epinephrine — stimulates metabolic activities, bronchial dilation, blood flow to muscle/heart
Norepinephrine — influences peripheral vasoconstriction and blood pressure

Homeostatic Imbalances
Hypersecretion — hyperglycemia, increased metabolic rate, rapid heartbeat/palpitations, hypertension, intense
nervousness, sweating
Hyposecretion — not problematic; adrenal catecholamines are not essential to life

31. Stress and the Adrenal Gland

Short-term stress response (via sympathetic nerves → adrenal medulla → catecholamines):
Increased heart rate, sodium/water retention by kidneys, increased blood pressure, bronchiole dilation, increased
blood volume/pressure

Long-term stress response (via hypothalamus → CRH → anterior pituitary → ACTH → adrenal cortex →
mineralocorticoids and glucocorticoids):
Proteins/fats converted to glucose or broken down for energy
Liver converts glycogen to glucose → blood glucose increases
Immune system suppressed
Blood flow changes reduce digestive activity and urine output
Metabolic rate increases

32. Pancreas

Anatomy
Located in the abdomen near the duodenum; both endocrine and exocrine gland
Exocrine — acinar cells produce digestive enzymes
Endocrine — pancreatic islets (islets of Langerhans)
Alpha cells — secrete glucagon
Beta cells — secrete insulin

Glucagon
Major target: liver
Causes increased blood glucose via:
Glycogenolysis — glycogen breakdown to glucose
Gluconeogenesis — glucose synthesis from lactic acid/noncarbohydrates
Release of glucose to blood

Secretion stimulated by low blood glucose

Insulin
Lowers blood glucose by:
Enhancing membrane transport of glucose into fat and muscle cells
Inhibiting glycogenolysis and gluconeogenesis
Also participates in neuronal development, learning, and memory

Not needed for glucose uptake in liver, kidney, or brain

Secretion stimulated by high blood glucose

Insulin Action Mechanism

 Activates the tyrosine kinase enzyme receptor
Cascade → increased glucose uptake
Triggers enzymes to:
Catalyze glucose oxidation for ATP production (first priority)
Polymerize glucose into glycogen
Convert glucose to fat (especially in adipose tissue)

Insulin Actions by Tissue

Tissue Effects

Liver Inhibits glucose production; increases glycogen synthesis; increases

fatty acid synthesis/esterification; decreases ketogenesis

Muscle Increases glucose uptake; increases glycogen synthesis; increases

protein synthesis; decreases protein degradation

Adipose tissue Increases glucose uptake; increases fatty acid

synthesis/esterification; decreases lipolysis

Factors That Influence Insulin Release

Elevated blood glucose (primary stimulus)
Rising blood amino acids and fatty acids
Acetylcholine release from parasympathetic nerve fibers
Hormones: glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids
Somatostatin and the sympathetic nervous system (inhibitory influences)

33. Diabetes Mellitus (DM)

Characterized by elevated plasma glucose (hyperglycemia), from interaction of genetic and environmental factors
Due to hyposecretion (Type 1) or hypoactivity/resistance (Type 2) of insulin

General Pathophysiology
High blood glucose → nausea → further glucose elevation (stress response)
Glycosuria — glucose spilled into urine
Fats used for fuel → lipidemia; if severe → ketones produced from fatty acid metabolism → ketonuria and ketoacidosis
Untreated ketoacidosis → hyperpnea, disrupted cardiac activity/O2 transport, CNS depression → coma, death possible

Three Cardinal Signs of DM

1. Polyuria — huge urine output (glucose acts as an osmotic diuretic)
2. Polydipsia — excessive thirst (from water loss via polyuria)
3. Polyphagia — excessive hunger/food intake (cells can’t take up glucose — “cellular starvation”)

DM Subtypes

Type 1A — insufficient insulin from pancreatic beta cell destruction, usually autoimmune; hyperglycemia often
worsened by elevated glucagon; may present with ketoacidosis, glycosuria, diuresis, coma
Type 1B — severe insulin deficiency without autoantibodies
Type 2 — accounts for up to 95% of DM cases; interaction of genetic/environmental factors; increasing prevalence in
children/adolescents
Risk factors: ethnicity, obesity, sedentary lifestyle, elevated triglycerides, family history, impaired fasting glucose
(IFG), impaired glucose tolerance (IGT)
Involves insulin resistance (precedes and increases DM risk) plus defective insulin secretion; hyperglycemia
associated with increased hepatic glucose production

MODY (Maturity Onset Diabetes of the Young) — genetic beta-cell defect; accounts for 1–5% of DM in young people

Principal Complications of DM
Stroke risk 2–4x higher
Leading cause of blindness in adults aged 20–74
 Leading cause of kidney disease
Neuropathies — ~60–70% of diabetics have nervous system damage
Impaired wound healing — >60% of nontraumatic lower-limb amputations

Hyperinsulinism
Excessive insulin secretion → hypoglycemia
Symptoms: anxiety, nervousness, disorientation, unconsciousness, even death
Treated by sugar ingestion

34. Ovaries and Testes (Gonads)

Ovaries
Located in the pelvic cavity
Produce estrogen and progesterone — regulate the female reproductive cycle and maintain pregnancy
Estrogen — maturation of reproductive organs, secondary sexual characteristics; with progesterone, drives breast
development and cyclic uterine mucosal changes
Placenta also secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)

Testes
Located in the scrotum
Produce testosterone and androgens — regulate sperm production
Testosterone: initiates male reproductive organ maturation, secondary sexual characteristics, sex drive; necessary for
normal spermatogenesis; maintains reproductive organs in a functional state

Both Gonads
Promote development of secondary sex characteristics
Produce inhibin, which inhibits FSH secretion

35. Pineal Gland

Small gland hanging from the roof of the third ventricle
Pinealocytes secrete melatonin, derived from serotonin
Melatonin blood levels rise during sleep
Melatonin may affect:
Timing of sexual maturation and puberty
Day/night (circadian) cycles
Physiological processes with rhythmic variation (body temperature, sleep, appetite)
Production of antioxidant/detoxification molecules in cells

Contributes to setting the body’s biological clock

36. Other Hormone-Producing Organs and Tissues

Organ/Tissue Hormone(s) Function

Adipose tissue Leptin Appetite control; increases energy

expenditure

Resistin Insulin antagonist

Adiponectin Enhances insulin sensitivity

GI tract (enteroendocrine cells) Gastrin Stimulates HCl release

Secretin Stimulates liver and pancreas

Cholecystokinin (CCK) Stimulates pancreas, gallbladder,

hepatopancreatic sphincter

Serotonin Acts as a paracrine

Heart Atrial natriuretic peptide (ANP) Decreases blood Na+, blood pressure, and
blood volume

Kidneys Erythropoietin Signals red blood cell production

Renin Initiates renin-angiotensin-aldosterone

mechanism

Skeleton (osteoblasts) Osteocalcin Prods pancreas to secrete more insulin;

restricts fat storage; improves glucose
handling; reduces body fat; activated by
insulin (low levels implicated in Type 2
diabetes)

Skin Cholecalciferol Precursor of vitamin D

Thymus Thymulin, thymopoietins, thymosins Involved in normal T lymphocyte

development; act as paracrines; gland is
large in children, shrinks with age

37. Developmental Aspects of the Endocrine System

Hormone-producing glands arise from all three germ layers
Most endocrine organs function well into old age
Environmental exposures (pesticides, industrial chemicals, arsenic, dioxin, water/soil pollutants) can disrupt hormone
function
Sex hormones, thyroid hormone, and glucocorticoids are particularly vulnerable
Glucocorticoid interference may help explain elevated cancer rates in certain areas

Ovaries — become unresponsive to gonadotropins with age; estrogen deficiency problems emerge
Testosterone — also declines with age, but effects usually not apparent until very old age
GH — declines with age, contributing to muscle atrophy
TH — declines with age, contributing to lower basal metabolic rate
PTH — levels remain fairly constant with age, but estrogen loss in older women increases vulnerability to PTH’s bone-
demineralizing effects

Quick-Review Summary
Hypothalamic-Pituitary Axis: hypothalamus (releasing/inhibiting hormones) → anterior pituitary (7 tropic/direct-
acting hormones via portal system) and posterior pituitary (stores/releases oxytocin & ADH made in hypothalamus)
Thyroid: TRH → TSH → T3/T4 (metabolism); calcitonin (↓Ca2+) from parafollicular cells
Parathyroid: PTH (↑blood Ca2+) — opposes calcitonin
Adrenal cortex: zona glomerulosa (mineralocorticoids/aldosterone — Na+/K+/BP), zona fasciculata
(glucocorticoids/cortisol — glucose/stress), zona reticularis (androgens)
Adrenal medulla: epinephrine/norepinephrine — sympathetic “fight-or-flight” amplification
Pancreas: alpha cells (glucagon, ↑glucose) vs. beta cells (insulin, ↓glucose) — antagonistic pair maintaining glucose
homeostasis
Gonads: ovaries (estrogen/progesterone), testes (testosterone) — reproduction and secondary sex characteristics
Pineal: melatonin — circadian rhythm
Key hormone actions: water-soluble hormones → membrane receptors → second messengers (cAMP, PIP2/Ca2+);
 lipid-soluble hormones → intracellular receptors → direct gene transcription

End of notes — based on Lecture 9: The Endocrine System (Pre-Matriculation), M.W. Burke, PhD. Diagram/table-only slides
(e.g., hormone summary tables, pathway diagrams, clinical photos of Cushing’s/acromegaly/Graves’ disease) are referenced
by title and incorporated where the slide or notes field contained explanatory text.