CHAPTER 16: THE ENDOCRINE SYSTEM
CELL-CELL COMMUNICATION
Electrical Signals - changes in the potential membrane (difference of charge between outside
and inside of the cell)
Chemical Signals – molecules secreted by cells into the extracellular fluid
Local Communication
(1) Gap Junctions: direct cytoplasmic connections between cells that allow for transfer of
electrical and chemical signals (i.e. ions, small molecules, amino acids, ATP, cAMP)
(2) Contact-Dependent Signals: require cell adhesion molecules (one w/ ligand, one w/
corresponding receptor) that bind together
(3) Autocrine Signals: chemicals that exert their effects on the cells that secrete them
(4) Paracrine Signals: chemicals secreted by one cell locally exert their effects on adjacent cells
of any type
Long Distance Cell-Cell Communication (regulated by Nervous and Endocrine Systems)
Endocrine System <---> Nervous System: coordinate and integrate activity of cells
Nervous System - fires action potentials that propagate along the axon and stimulate the release
of neurotransmitters (electrical signals  chemical signals)  rapid, short responses
Endocrine System - endocrine cells in an organ secrete hormones into nearest blood vessel at
any location and bind to target cells of another organ (chemical signals)  slow, long responses
GLANDS
Exocrine Glands – secrete non-hormonal substances (i.e. sweat, saliva) via simple tubular or
simple branched alveolar ducts that lead to membrane surface
- Formed by invagination of epithelial cells within connective tissue
Endocrine Glands – produce hormones that secrete directly into the bloodstream without ducts
- Formed by degradation of epithelial cells near the inner membrane surface & infiltration
of epithelial cells by blood capillaries
EXAMPLES OF PURELY ENDOCRINE GLANDS: pituitary gland, thyroid & parathyroid glands,
adrenal gland, pineal gland
ENDOCRINE-EXOCRINE GLANDS (scattered endocrine tissues): pancreas (exo  enzymes,
endo  insulin hormone), gonads (exo  sperm, endo  sex hormones), placenta (exo 
nutrients from mother to fetus, endo  pregnancy hormones)
NEUROENDOCRINE GLANDS: hypothalamus
Functions of Endocrine System:
1. Reproduction
2. Growth & Development
3. Homeostasis of electrolyte/water/nutrients in blood
4. Regulation of cellular metabolism and energy
5. Body defenses
Hormones
Hormones – chemical messengers secreted into the bloodstream at very low concentrations
(think nanomolar^-9 to picomolar^-12) that stimulate physiological responses in endocrine
organs
 Influence metabolic activities
 Responses are slower but longer-lasting than those of the nervous system
Amino Acid-Based Hormones – water-soluble hormones excluding thyroid hormones (i.e.
amino acid derivatives, peptides, proteins) held in vesicles that are made in many tissues
- Easily transported in blood due to their solubility
- Unable to pass through plasma membrane and enter cells
- Short half-life (minutes) since these hormones can be removed by kidneys
- Act on cell-surface (membrane) receptors & second-messenger systems
o Cyclic AMP second-messenger mechanism (signal transduction 
amplification of hormone ligands)
1) Hormone (1st messenger) binds to its membrane receptor.
2) Receptor activates G-protein on GPCR by binding GTP and displacing
GDP.
3) G-protein activates adenylate cyclase.
4) Adenylate cyclase converts ATP to cAMP (2nd messenger)
5) cAMP activates protein kinase A  phosphorylation cascade of target
proteins
6) cAMP is rapidly degraded by the enzyme phosphodiesterase (PDE).
 Calcitonin  increase breakdown of bone tissue via osteoclast activity
 Glucagon  increase blood glucose via liver
 Norepinephrine/Epinephrine  muscle relaxation & cardiac contraction via
adrenergic receptors
o Calcium second-messenger mechanism
1) Hormone (1st messenger) triggers conformational change in receptor.
2) Receptor activates G-protein on GPCR by binding GTP and displacing
GDP.
3) G-protein activates the enzyme phospholipase C (PLC)
4) PLC uses hydrolysis to cleave the phospholipid PIP2 into inositol
triphosphate (IP3) and diglyceride (DAG), which act as 2nd messengers
5) IP3 functions as voltage-gated Ca+2 ion channels to triggers Ca+2
release into cytosol
6) Ca+2 ions from ECF (third 2nd messenger) bind to proteins calmodulin
and protein kinase C (PKC)
7) Ca-bound calmodulin activates protein kinases & ATPases  cross
bridges form between myosin and actin (smooth muscle contraction)
8) PKC triggers phosphorylation cascade of target proteins to amplify
response.
 Oxytocin  activates Ca+2 signaling to induce uterine contractions
 GnRH  targets proteins involved in FSH/LH synthesis
Steroids – lipid-soluble hormones (i.e. testosterone, estradiol) synthesized from cholesterol that
are produced in only a few organs such as gonads & adrenal glands
- Lipid-soluble hormones include thyroid hormones formed by thyroid gland
- Must bind to transport protein to enter bloodstream
- Pass through plasma membrane to enter cells
- Long half-life since these hormones need to be metabolized by liver
- Act on intracellular receptors in cytoplasm or nucleus to form complex hormonereceptor to directly activate genes
o Direct Gene Activation  synthesis of new proteins
1) Steroid hormone diffuses through membrane to bind to intracellular
receptor.
2) Receptor-hormone complex enters the nucleus and binds to specific genes
 initiation of gene transcription
3) mRNA synthesizes proteins.
MECHANISMS OF HORMONES: results of 1) cAMP mechanism, 2) smooth muscle contraction,
and 3) direct gene activation
-
Although hormones circulate throughout the bloodstream, a hormone will only affect the
target cells (cells with receptors for that specific hormone)
Hormones alter the activities of their target cells by:
o Alter membrane permeability (thus altering membrane potential) by opening or
closing ion channels
o Stimulate synthesis of enzymes and proteins
o Stimulate mitosis (i.e. form new cells to replace those lost during the
menstruation cycle)
o Activate or de-activate enzymes
o Induce secretory activity
Target Cells – cells that have specific receptors to which a hormone can bind to
- Depends on
o Blood levels of hormone
o Relative number of receptors on/in target cell
 Up-regulation: increase number of receptors
 Down-regulation: reduce number of receptors to prevent over-stimulation
o Ligand-receptor affinity
- ACTH receptors found only on certain cells of adrenal cortex
- Thyroxin receptors found on nearly ALL CELLS of body
Hormone Release – blood levels of hormones reflect release rate and speed of
inactivation/removal & are controlled by negative feedback systems
- Humoral Stimuli: changing blood/ECF levels of ion and nutrients directly stimulate
hormone secretion
o Calcium homeostasis: falling blood Ca+2 levels  parathyroid glands release
PTH  osteoclasts degrade bone matrix to release Ca+2 into blood
- Neural Stimuli: neural input causes hormone release
o Norepinephrine/Epinephrine release: action potentials in preganglionic
sympathetic nerve fibers (axons) stimulate adrenal medulla
-
Hormonal Stimuli: a tropic hormone from an endocrine gland stimulates other
endocrine glands to induce hormone secretion
o Hypothalamus  Pituitary Gland  (1) Thyroid Gland, (2) Adrenal
Cortex, (3) Gonads
Hormone Removal – two mechanisms:
1) Degrading enzymes in kidneys and liver inactivate metabolites, which are then excreted
in urine or bile
2) Receptor-hormone complex is brought into cell by endocytosis and hormone is digested
in lysosomes
Interaction of Hormones & Target Cells –
- Permissiveness: one hormone can only exert its effects with another hormone present
- Synergism: multiple hormones produce same effects on target cell  amplification
(i.e. glucose levels (glucagon + epinephrine + cortisol) > glucose levels (only glucagon or
only epinephrine)
- Antagonism: one or more hormones oppose the action of another hormone
HYPOTHALAMIC AND PITUITARY HORMONES
Diencephalon: thalamus, hypothalamus, pineal gland, pituitary gland
Main Hypothalamic Nuclei: paraventricular nucleus, supraoptic nucleus, suprachiasmatic
nucleus, mamillary body
Pituitary Gland (Hypophysis) – composed of (1) posterior pituitary lobe made of neural tissue
and (2) anterior pituitary (adenohypophysis) lobe made of glandular tissue
Posterior Pituitary Lobe (PPL) - paraventricular & supraoptic nuclei synthesize oxytocin or
ADH, which are transported down the nerve fibers (axons) of the hypothalamic tract to the
posterior pituitary lobe  PPL stores oxytocin & ADH and releases them upon action potentials
from hypothalamus
- Oxytocin/ADH: each composed of 9 amino acids that only differ by 2 amino acids,
produced by paraventricular & supraoptic nuclei
o Oxytocin: targets uterus
 strong stimulant of uterine contraction released at childbirth via positive
feedback loop (more contractions  more oxytocin)
 Triggers milk ejection
 Increases during sexual arousal and orgasm (propulsion of semen
through male reproductive tract, uterine contractions in female
reproductive tract)
 Facilitates emotional and maternal bonding
o Anti-Diuretic Hormone (Vasopressin): high concentrations 
vasoconstriction that targets kidneys
 Inhibits urine production
 Regulates water homeostasis (targeting kidney tubules  kidney cells
reabsorb more H2O into blood to make up for water lost in urine)
 Triggered by pain, low blood pressure, high concentration of solutes in
blood, and drugs (nicotine, morphine, barbiturates)
 Inhibited by alcohol, diuretics, and water
- Homeostatic Imbalances (Clinical)
o
o
Diabetes Insipidus (NOT your typical diabetes): ADH deficiency due to
damage to hypothalamus or posterior pituitary lobe  abnormal levels of
electrolytes and sodium
 Must keep well-hydrated
Syndrome of Inappropriate ADH Secretion (SIADH): hypersecretion of
ADH caused by tumors in hypothalamus  fluid retention, headaches,
disorientation
 Restrict fluids
 Monitor sodium levels
Hypothalamus-Hypophyseal Tract – hypothalamus  pituitary gland via portal veins
- Hypothalamic Hormones: tropic hormones synthesized by hypothalamic neurons 
controls the release of hormones from the anterior pituitary lobe (APL)
o PIH (prolactin-inhibiting hormone AKA dopamine)  inhibit prolactin
o GHIH (growth hormone-inhibiting hormone)  releases growth hormone
o GnRH (gonadotropin-releasing hormone)  releases gonadotropin (i.e. FSH &
LH)
o TRH (thyrotropin-releasing hormone)  releases TSH
o CRH (corticotropin-releasing hormone)  releases ACTH
- Anterior Pituitary Lobe Hormones: tropic hormones synthesized by APL
o Prolactin  produces milk production via mamillary gland
o GH (growth hormone)  supports cellular growth throughout body
o FSH (follicle-stimulating hormone)  releases estrogen in ovaries and
maturation of stem cells in both testes & ovaries
o LH (luteinizing hormone)  stimulates progesterone & testosterone in gonads
o TSH (thyroid-stimulating hormone)  release T4 or T3 hormones in thyroid
o ACTH (adrenocorticotropin hormone)  stimulates aldosterone, cortisol,
glucocorticoid production in adrenal cortex and norepinephrine, epinephrine in
adrenal medulla
THYROID HORMONES
Thyroid Gland - two lateral lobes connected by the isthmus
- Follicular cells produce and store the glycoprotein thyroglobulin
o Colloid (thyroglobulin + iodine  precursor of thyroid hormone) fills cavity
(lumen) of follicles
- Parafollicular cells produce the hormone calcitonin  calcium homeostasis
Thyroid Hormone
Thyroid Hormone (TH) – major metabolic hormone that includes T4 (thyroxine) and T3
(triiodothyronine)
- T4 Hormone = 2 tyrosine molecules + 4 bound iodine atoms
- T3 Hormone = 2 tyrosine molecules + 3 bound iodine atoms
 Increase metabolic rate & heat production
 Regulation of tissue growth & development (i.e. skeletal, nervous, reproductive systems)
 Maintenance of blood pressure
Synthesis of TH – mediated by TSH and TRH, with thyroid gland storing hormones
extracellularly
1) Thyroglobulin with attached tyrosines is synthesized and secreted into the follicular
lumen
2) Uptake of iodide (I-) ions into the cell and released into the lumen (colloid)  iodide (I-)
is oxidized to iodine (I2)
3) Iodine (I2) attaches to tyrosine via peroxidase enzymes to form iodinated tyrosines
4) Iodinated tyrosines are linked together to form T3 and T4 hormones
5) Thyroglobulin is absorbed by vesicles and fused to lysosomes for digestion
6) Following digestion, T3 and T4 hormones are released into circulation
Transport and Regulation of TH – T3/T4 are transported by thyroxine-binding globulins
(TBGs)
- Although both bind to target receptors, T3 is 10 times more active than T4 even though
the blood concentration levels of T4 are greater than T3
- Peripheral tissues convert T4 to T3
- Negative Feedback Regulation (rising TH levels  inhibits TH release)
o HOWEVER: thyrotropin-releasing hormone (TRH) released by hypothalamus to
stimulate TSH (and thus TH) can overcome negative feedback during 1)
pregnancy and 2) exposure to cold temperatures
- Homeostatic Imbalances (Clinical)
o Caused by hypothyroidism:
 Myxedema: severe hypothyroidism
 Goiter: lack of iodine caused by hypothyroidism excessive stimulation
of thyroid gland to produce TSH and hypothalamus to produce TRH
 Cretinism: hypothyroidism in infants
o Caused by hyperthyroidism  increased body temperature & blood pressure
 Graves’ disease: an autoimmune disease that produces antibodies that
bind to follicular cells to mimic TSH to over-stimulate thyroid gland
Calcitonin – a hormone produced by parafollicular cells that functions as an antagonist to PTH
 Inhibits osteoclast activity and release of Ca+2 from bone matrix
 Stimulates Ca+2 uptake into bone matrix, leading to a decrease in blood Ca+2 levels
Parathyroid Hormone (PTH) – controlled by negative feedback (rising Ca+2 levels in blood 
inhibits PTH release)
- Hypocalcemia: low blood Ca+2 levels  PTH release to increase blood Ca+2 levels
- Hypoparathyroidism (caused by gland trauma/removal or dietary Mg deficiency):
causes nervous system dysfunction (much lower action potential is needed to open Na+
channels, causing overfiring)  tetany, respiratory paralysis, and death
- Hyperparathyroidism (caused by tumors): leads to softened and deformed bones &
elevated Ca+2 levels  leads to nervous system dysfunction and contributes to kidney
stone formation
 Stimulates osteoclast activity, which releases Ca+2 from bone matrix into blood
 Activates synthesis of vitamin D in kidneys
 Basically the opposite function of calcitonin
ADRENAL HORMONES
Adrenal glands: located on top of kidneys
Adrenal Cortex - outer region of adrenal gland
- Types of Hormones  Al-G, C-F, An-R
Aldosterone (zona glomerulosa): steroid hormone that targets distal tubules of
kidneys that acts via renin-angiotensin-aldosterone mechanism to activate
Na+/K+ pumps, leading to increases in blood pressure and volume
 Reabsorption of Na+ ions and water into blood
 Excretion of K+ ions in urine
o Cortisol (zona fasciculata): a glucocorticoid that is released in response to stress
and low glucose concentrations
 Increases blood sugar through gluconeogenesis
 Suppresses immune system
 Metabolism of fat, protein, and carbohydrates
 Decreases bone formation
o Androgens (zona reticularis): male sex hormones present in both males and
females including testosterone
 In females: libido and sexual arousal
 In males: differentiation of male sex organs in utero, facial and body hair
growth & voice change during puberty
 Stimulates bone and muscle development
Homeostatic Imbalances (Clinical)
o Addison’s Disease (hypoadrenalism): cortisol deficiency leading to high levels
of ACTH  weight loss, decreased appetite, low blood pressure that can cause
fainting, hyperpigmentation
o Cushing’s Disease (hyperadrenalism): excessive amounts of cortisol caused by
tumors on pituitary gland or adrenal cortex  rounded face, buffalo hump
o
-
Adrenal Medulla - inner region of adrenal gland hat produces epinephrine and
norepinephrine
- Body’s Response to Stress:
1. Hypothalamus triggers action potentials in response to stressors activating SNS
2. Preganglionic sympathetic nerve fibers propagate action potential to adrenal
medulla
3. Adrenal medulla secretes norepinephrine and epinephrine  reinforcement of
“fight-or-flight” response
PANCREATIC HORMONES
Pancreas - located in abdomen & produces peptide hormones
- Hormones of Alpha Cells: glucagon that targets liver
o Glucagon: stimulated by glycogenolysis/gluconeogenesis to raise
concentrations of glucose & fatty acids in bloodstream
 Glycogenolysis: glycogen  glucose
 Gluconeogenesis: lactic acid  glucose
 Promotes uptake of amino acids into liver
- Hormones of Beta Cells: insulin that targets liver, muscle, and fat
o Insulin: stimulated mainly by elevated blood glucose levels but also by rising
levels of amino acids, the release of acetylcholine, glucagon, and GHIH
 Uptake of glucose into target cells
 Uptake of amino acids into muscle cells to increase DNA replication and
protein synthesis
 Glycogenesis: storage of glucose in the form of glycogen (as well as
breakdown of glycogen)
 Conversion of amino acids/fats into glucose
-
-
Homeostatic Imbalances (Clinical)
o Type 1 Diabetes: hyposecretion of insulin (insufficient production)  increased
thirst, frequent urination, weight loss
o Type 2 Diabetes: hypoactivity of insulin (insulin resistance)  numbness in
hands/feet, slow development of symptoms
o Hyperinsulinemia: excess levels of insulin  weight gain, sugar cravings
Clinical Terminology
o Glycosuria: excess glucose in urine
o Polyuria: huge urine output
o Polydipsia: excessive thirst
o Polyphagia: excessive hunger
Ketones – acidic molecules formed due to fatty acid metabolism when sugars are unable to be
used as fuel
- Ketoacidosis: build-up of ketones in blood  similar symptoms to diabetes, as well as
hyperpnea (increased depth/rate of breathing), disrupted heart activity, and depressed
nervous system