The Endocrine System
- Two major controlling systems in the body : nervous and endocrine.
- Nervous system regulates the activity of muscle and glands by means of
electrochemical impulses delivered by neurons.
- The endocrine system influences the metabolic activities of cells by
means of hormones (chemical messengers).
- The endocrine glands are ductless glands and include pituitary, thyroid,
parathyroid, adrenal, pineal, and thymus.
- Organs (Diagram) that contain endocrine tissue include the
pancreas, gonads (testes and ovaries) and digestive organs (stomach and intestines, enteroendricine tissue).
- Pituitary secretions regulated by neuroendocrine gland, the hypothalamus.
- Hormones - chemical substances secreted by cells into the extracellular
fluids and regulate the metabolic function of other cells in the body
- Two chemical classes: Diagram
- Amino acid based - protein, peptide, and catecholamines (epinephrine and
- Steroids - most hormones synthesized from cholesterol (but some may be derived from linoleic acid and arachidonic acid)
A. Hormone-Target Cell Specificity
- Hormone is received by a target cell and evokes a response
- Cell response is dependent upon protein receptors on the plasma membrane
or receptors in the nucleus and if receptors present, will bind hormones complimentarily
- Extent of target-cell activation (response) by hormone-receptor
interaction depends on....
- blood levels of the hormone
- relative numbers of receptors for the specific hormone
- affinity for the hormone by receptor
- Regulation of cell receptors:
- Up regulation - increase in the number of receptors with increase in
- Down regulation - prolonged exposure, cells become desensitized and there
is a loss of receptors
B. Mechanism of Hormone Action
- A hormonal stimulus typically produces one or more of the following
- changes in plasma membrane permeability and/or electrical state (membrane
- synthesis of proteins or certain regulatory molecules (such as enzymes)
within the cell
- enzyme regulation (activation or deactivation)
- induce secretion
- stimulation of mitosis
- Two major mechanisms leading to hormone action:
- Second messenger systems (mediate the target cell's response to hormone) Diagram
- Hormone binds to a receptor on the cell membrane
- Receptor causes adenylate cyclase in the membrane to be active and
convert ATP into cAMP
- cAMP activates protein kinases
- Protein kinases activates enzymes, stimulate cellular secretion, opens
ion channels, etc.....
- Direct gene activation Diagram
- Steroid hormones diffuse easily into their target cells
- They bind to receptors within the nucleus
- The activated complex then interacts with the nuclear chromatin binding
to a receptor protein
- Binding to chromatin "turns on" DNA Transcription of mRNA which
is used to direct the synthesis of other proteins (e.g. enzymes).
C. Control of Hormone Release
- Synthesis and release of most hormones are regulated by some type of
negative feedback Diagram
- The output of the system feeds back and decreases the input into the
- Three types of stimuli that initiates/stimulates the manufacture and
release of hormones:
- Hormonal - hypothalamus produces releasing and inhibiting hormones Diagram
- Humoral - changing in blood levels of ions and nutrients
- Neural - neuronal control (e.g. sympathetic nervous system release of
catecholamines during stress)
III. Endocrine Organs of the Body
A. Pituitary Gland (Hypophysis) Diagram
- Housed in the sella turcica of the sphenoid bone
- Pituitary is connected the hypothalamus by the infundibulum and is
divided into two lobes:
- posterior lobe (neurohypophysis) - neuroglia and nerve fibers release
neurohormones premade from hypothalamus
- anterior lobe (adenohypophysis) - glandular tissue
- posterior lobe - infundibulum and pars nervosa
- anterior lobe - pars tuberalis (superior portion) and pars distalis
- Pituitary-Hypothalamic Relationships Diagram
- Neurohypophysis Diagram
- Connected with hypothalamus via a nerve bundle (hypothalamic-hypophyseal
tract) which runs through the infundibulum
- The tract arises from neurons in the supraoptic (releases hormone ADH)
and paraventricular (releases hormone oxytocin) nuclei of the hypothalamus.
- Adenohypophysis Diagram
- No neural connection, rather vascular connection
- Primary capillary plexus communicates with the secondary capillary plexus
via hypophyseal portal veins within the infundibulum
- Primary and secondary plexus and hypophyseal portal vein are collectively
called the hypophseal portal system which secretes releasing and inhibiting hormones from
neurons in the ventral hypothalamus.
- Adenohypophyseal hormones (all are secon messenger hormones) - six
distinct adenohypophyseal hormones:
- (GH) - growth hormone
- (PRL) - prolactin
- Tropic (regulates the hormone function of other endocrine glands)
- (TSH) - thyroid-stimulating
- (ACTH) - adrenocorticotropic
- gonadotropic (regulate thefunction of gonads)
- (FSH) - follicle-stimulating
- (LH) - luteinizing
B. Thyroid Gland
- Butterfly-shaped and largest endocrine gland located in the anterior neck
overlying the trachea just inferior to the larynx.
- The thyroid gland has two lateral lobes connected by a medial tissue mass
called the isthmus.
- Thyroid gland composed of follicles which are concentric rings of cells
with a lumen.
- The walls of each follicle formed largely by cuboidal epithelial cells
which produce the glycoprotein thyroglobulin.
- Iodinated thyroglobulin is used to synthesize two thyroid hormones
(thyroxin and triodothyronine) which are collectively called thyroid hormone.
- Thyroxine (T4) and triodothyronine (T3) - thyroid hormone stimulates
enzymes concerned with glucose oxidation and therefore increases basal metabolic rates and
heat production (calorigenic effect)
- Synthesis of thyroid hormone:
- Thyroglobulin synthesis - TSH is secreted and sent to
follicle cells in the thyroid. Thyroglobulin is synthesized on ribosomes and sent to golgi
where sugar residues are attached. Thyroglobulin is then packed into vesicle, transported
to the apex of the cell, and discharged into the lumen of the follicle.
- Iodine attachment - cells accumulate iodides and convert
them to iodine which attach to tyrosine aminoacids of thyroglobulin (results in
monoiodotyrosines, MIT, and diiodotyrosines, DIT). Enzymes link iodotyrosines: MIT + DIT =
T3 and DIT + DIT = T4. Hormones are still part of the colloid and need to be cleaved to be
- Hormone Cleavage - follicle cells reclaim iodinated
thyroglobulin by endocytosis and packaged in lysosomes - lysosomal enzymes cleave T3 and
T4 which diffuse into the blood stream.
- NOTE: some T4 is converted to T3 before secretion BUT
most T3 is generated in the peripheral tissues
- T3 and T4 are second messenger hormones
- Calcitonin (thyrocalcitonin) - polypeptide hormone produced by the
parafollicular (C cells) cells of the thyroid gland. Calcitonin lowers blood calcium and
phosphate levels and is a direct antagonist of parathyroid hormone.
C. Parathyroid Diagram
- Embedded on the posterior surface of the lobes of the thyroid gland
- Secretes parathyroid hormone (PTH)/parathormone
- PTH controls the calcium balance of the blood and is triggered by
increased calcium levels or inhibitd by hypercalcemia
- PTH stimulates three target organs: skeleton, kidneys, and intestines.
- PTH release results in...
- Activation of osteoclasts to digest bony matrix and release calcium ions
- Enhanced resorption of calcium ions
- Increased absorption of calcium by intestinal mucosal cells
D. Adrenal Gland (Suprarenal)
- Pyramid-shaped organs located at superior border of each kidney and is
surrounded by connective tissue and embedded in fat
- There two separate portions: inner medulla and an outer cortex.
- Adrenal Cortex
- Synthesizes steroid hormones (corticosteroids) from cholesterol
- Cortical cells arranged in three concentric regions:
- zona glomerulosa - produces mineralcorticoids (Aldosterone) that control
the balance of minerals and water
- zona fasciculata - (linear cords) produce glucocorticoids (cortisol)
- zona reticularis - produc glucocorticoids (cortisol) and gonadocorticoids
- Mineralocorticoids - regulation of electrolyte concentrations in
extracellular fluids. 95% of all mineralocorticoids produced is aldosterone which promotes
sodium reabsorption from urine in kidneys and regulates some electrolyte concentrations.
Four mechanisms involved in regulation of aldosterone secretion:
- Renin-angiotensin system - juxtaglomerular apparatus (in kidney) releases
the enzyme renin in response to decreased blood pressure or decrease in plasma osmolarity.
Renin cleaves angiotensinogen which causes an enzymatic cascade leading to the formation
of angiotensin II. Angiotensin II stimulates aldosterone release.
- Sodium and Potassium concentrations- increased potassium and decreased
sodium stimulates aldosterone secretion.
- ACTH - in response to stress, hypothalamus secretes more corticotropin
releasing hormone(CRH) which increases ACTH blood levels, thereby increasing aldosterone
- Atrial Natiuretic Factor (ANF) - ANF is a hormone secreted by the heart
when blood pressure rises (as a result of sodium-water imbalance) and inhibits the
- Glucocorticoids - influences metabolism. Its secretion is stimulated by
ACTH/CRH. Examples are cortisol (hydrocortisone), cortisone, and corticosterone.
- Gonadocorticoids - sex hormones, androgens (testosterone), some estrogens
- Adrenal Medulla
- Contains chromaffin cells arranged in irregular clusters and is
stimulated by sympathetic preganglionic fibers
- Adrenal medulla secretes epinephrine (adrenaline) and norepinephrine
- The catechlolamines secreted increase heart rate and blood pressure (via
E. Pancreas Diagram
- Contains acinar cells that produce enzymes that are ducted into the small
intestine, therefore is a exocrine gland
- Among the acinar cells are islets of Langerhans that produce pancreatic
hormones, therefore endocrine gland
- Cells of islets of Langerhans:
- Alpha cells - glucagon-synthesizing (hyperglycemic hormone)
- Beta cells - insulin-synthesizing (hypoglycemic hormone)
- Produce gonadal sex hormones:
- Ovaries - estrogens and progesterone
- Testes - testosterone
G. Pineal Gland Diagram
- Roof of third ventricle within the diencephalon and contains pinealocytes
- Secrete melatonin.
- May be involved in sleep-wake cycle
I. Hormone Overview: Diagram
- Thymic epithelial cells secrete the peptide hormones thymopoeitin and
thymosin used in the development of immunity
IV. Clinical Terms Diagram
- Acromegaly - excessive production of GH (due to tumor production)
- Galactorrhea - production of milk whether needed or not (possibly due to medication or tumors such as prolactinomas)
- Cushing's syndrome - pituitary adenomas increases production of
ACTH which causes adrenal gland to increase production of cortisol;
manifests as "moon face," "buffalo hump," and striae
- Myxedemia - decrease in function of thyroid resulting from TSH and TRH
- Endemic goiter - thyroid gland enlarges as a result of lack of iodine
(follicle accumulates unusable colloid)
- Cretinism - genetic deficiency of fetal thyroid gland in
infantsGrave's disease - antibodies act against component of follicle
cell membrane (decrease secretion of thyroid hormone)
- Addisons disease - hyposecretion of glucocorticoids and mineralcorticoids
- Cushing's disease - caused by tumor within adrenal
cortex causes increase production of cortisol
- Hyperparathyroidism - results from gland tumor, increases blood calcium
levels and causes depressed nervous system and kidney stones
- Hypoparathyroidism - results in PTH deficiency and causes increase in
excitability of neurons
- Diabetes mellitus - two types: Type I (IDDM) - no insulin
activity - increase blood glucose levels; Type II (NIDDM) - inadequate
amount of insulin or problem with insulin receptors
- Hyperinsulinism - excessive excretion of insulin, results in decreased
blood glucose levels, hypoglycemia.