11/26/2007
1
Principles of Human Anatomy and Physiology, 11e 1
The Endocrine System
Lecture Series
Principles of Human Anatomy and Physiology, 11e 2
The Endocrine System
• The nervous and endocrine systems act as a coordinated interlocking supersystem, the neuroendocrine system.
• The endocrine system controls body activities by releasing mediator molecules called hormones.
– hormones released into the bloodstream travel throughout the body
– results may take hours, but last longer
• The nervous system controls body actions through nerve impulses.
– certain parts release hormones into blood
– rest release neurotransmitters--excite or inhibit nerve, muscle & gland cells
– results in milliseconds, brief duration of effects
Principles of Human Anatomy and Physiology, 11e 3
NERVOUS and ENDOCRINE SYSTEM
• The nervous system causes muscles to contract or glands to secrete. The endocrine system affects virtually all body
tissues by altering metabolism, regulating growth and development and influencing reproductive processes.
• Parts of the nervous system stimulate or inhibit the release
of hormones.
• Hormones may promote or inhibit the generation of nerve impulses.
11/26/2007
2
Principles of Human Anatomy and Physiology, 11e 4
General Functions of Hormones
• Help regulate:
– extracellular fluid
– metabolism
– biological clock
– contraction of cardiac & smooth muscle
– glandular secretion
– some immune functions
• Growth & development
• Reproduction
• Hormones have powerful effects when present in very low concentrations.
Principles of Human Anatomy and Physiology, 11e 5
Endocrine Glands Defined• Exocrine glands
– secrete products into ducts which empty into body cavities or body surface
– sweat, oil, mucous & digestive glands
• Endocrine glands
– secrete products (hormones) into bloodstream
– pituitary, thyroid, parathyroid, adrenal, pineal
– other organs secrete hormones as a 2nd function
– hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach, liver, small intestine, skin, heart
& placenta
Principles of Human Anatomy and Physiology, 11e 6
Hormone Receptors
• Hormones only affect target cells with specific membrane proteins called receptors
11/26/2007
3
Principles of Human Anatomy and Physiology, 11e 7
Hormone Receptors
• Although hormones travel in blood throughout the body, they affect only specific target cells.
– Target cells have specific protein or glycoprotein receptors to which hormones bind.
• Receptors are constantly being synthesized and broken down.
• Synthetic hormones that block the receptors for particular naturally occurring hormones are available as drugs. (Clinical Application)
Principles of Human Anatomy and Physiology, 11e 8
Regulation of Hormone Receptors
• Receptors are constantly being synthesized & broken down
– range of 2000-100,000 receptors / target cell
• Down-regulation
– excess hormone leads to a decrease in number of receptors
• receptors undergo endocytosis and are degraded
– decreases sensitivity of target cell to hormone
• Up-regulation
– deficiency of hormone leads to an increase in the number of receptors
– target tissue becomes more sensitive to the hormone
Principles of Human Anatomy and Physiology, 11e 9
Circulating and Local Hormones
• Hormones that travel in blood and act on distant target cells are called circulating hormones or endocrines.
• Hormones that act locally without first entering the blood stream are called local hormones.
– Those that act on neighboring cells are called paracrines.
– Those that act on the same cell that secreted them are
termed autocrines.
11/26/2007
4
Principles of Human Anatomy and Physiology, 11e 10
Circulating & Local Hormones
• Circulating hormones
• Local hormones
– paracrines
– autocrines
Principles of Human Anatomy and Physiology, 11e 11
Chemical Classes of Hormones
• Lipid-soluble hormones include the steroids and thyroid hormone.
• Water-soluble hormones include the amines--peptides,
proteins and glycoproteins
Principles of Human Anatomy and Physiology, 11e 12
Lipid-soluble Hormones
• Steroids
– lipids derived from cholesterol on SER
– different functional groups
attached to core of structure provide uniqueness
• Thyroid hormones
– tyrosine ring plus attached
iodines are lipid-soluble
• Nitric oxide is gas
11/26/2007
5
Principles of Human Anatomy and Physiology, 11e 13
Water-soluble Hormones
• Amine, peptide and protein hormones
– modified amino acids or amino acids put together
– serotonin, melatonin, histamine, epinephrine
– some glycoproteins
• Eicosanoids
– derived from arachidonic acid (fatty acid)
– prostaglandins or leukotrienes
Principles of Human Anatomy and Physiology, 11e 14
Hormone Transport in Blood
• Protein hormones circulate in free form in blood
• Steroid (lipid) & thyroid hormones must attach to transport proteins synthesized by liver
– improve transport by making them water-soluble
– slow loss of hormone by filtration within kidney
– create reserve of hormone
• only 0.1% to 10% of hormone is not bound to transport protein = free fraction
Principles of Human Anatomy and Physiology, 11e 15
General Mechanisms of Hormone Action
• Hormone binds to cell surface or receptor inside target cell
• Cell may then
– synthesize new molecules
– change permeability of membrane
– alter rates of reactions
• Each target cell responds to hormone differently
At liver cells---insulin stimulates glycogen synthesis
At adipocytes---insulin stimulates triglyceride synthesis
11/26/2007
6
Principles of Human Anatomy and Physiology, 11e 16
Action of Lipid-Soluble Hormone
• Lipid-soluble hormones bind to and activate receptors within cells.
– The activated receptors then alter gene expression which results in the formation of new proteins.
– The new proteins alter the cells activity and result in the physiological responses of those hormones.
Principles of Human Anatomy and Physiology, 11e 17
Action of Lipid-Soluble Hormones
• Hormone diffuses through phospholipid bilayer & into cell
• Binds to receptor turning on/off specific genes
• New mRNA is formed & directs synthesis of new proteins
• New protein alters cell’s activity
Principles of Human Anatomy and Physiology, 11e 18
Action of Water-Soluble Hormones
• Water-soluble hormones alter cell functions by activating plasma membrane receptors, which set off a cascade of
events inside the cell.
– The water-soluble hormone that binds to the cell
membrane receptor is the first messenger.
– A second messenger is released inside the cell where
hormone stimulated response takes place.
• A typical mechanism of action of a water-soluble hormone is using cyclic AMP as the second messenger.
11/26/2007
7
Principles of Human Anatomy and Physiology, 11e 19
Action of Water-Soluble Hormones
• Can not diffuse through plasma membrane
• Hormone receptors are integral membrane proteins
– act as first messenger
• The hormone binds to the membrane receptor.
• The activated receptor activates a membrane G-protein which turns on adenylate cyclase.
• Adenylate cyclase converts ATP into cyclic AMP which activates protein kinases.
• Protein kinases phosphorylate enzymes which catalyze reactions that produce the physiological response.
Principles of Human Anatomy and Physiology, 11e 20
HYPOTHALAMUS AND PITUITARY GLAND
• The hypothalamus is the major integrating link between the nervous and endocrine systems.
– Hypothalamus receives input from cortex, thalamus, limbic system & internal organs
– Hypothalamus controls pituitary gland with 9 different releasing & inhibiting hormones
• The hypothalamus and the pituitary gland (hypophysis)
regulate virtually all aspects of growth, development, metabolism and homeostasis.
Hypothalamus and Pituitary Gland
• Releasing hormones—hormones elaborated in one structure that effect the release of hormones from another
structure
• -tropin –a word termination denoting affinity for the structure
or thing indicated by the stem to which it is affixed
• Tropic hormone—means that the target organs are other
endocrine cells (FSH—gonads)
• Hyposecretion—diminished secretion of a gland
• Hypersecretion—excessive secretion
Principles of Human Anatomy and Physiology, 11e 21
11/26/2007
8
Principles of Human Anatomy and Physiology, 11e 22
• The pituitary gland is located in the sella turcica of the sphenoid bone and is differentiated into the anterior pituitary
(adenohypophysis), the posterior pituitary (neurohypophysis)
and pars intermedia (avascular zone in between).
• Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid
– Infundibulum attaches it to brain
• Anterior lobe = 75%
– develops from roof of mouth
• Posterior lobe = 25%
– ends of axons of 10,000 neurons found in hypothalamus
Anatomy of Pituitary Gland
Principles of Human Anatomy and Physiology, 11e 23
Anterior Pituitary Gland (Adenohypophysis)
• The blood supply to the anterior pituitary is from the superiorhypophyseal arteries.
• Hormones of the anterior pituitary and the cells that produce the:
– Human growth hormone (hGH) is secreted by somatotrophs.
– Thyroid-stimulating hormone (TSH) is secreted by thyrotrophs.
– Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotrophs.
– Prolactin (PRL) is secreted by lactrotrophs.
– Adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating
hormone (MSH) are secreted by corticotrophs.
Principles of Human Anatomy and Physiology, 11e 24
Flow of Blood to
Anterior Pituitary
• Controlling hormones enter blood
• Travel through portal veins
• Enter anterior pituitary at capillaries
11/26/2007
9
Principles of Human Anatomy and Physiology, 11e 25
Anterior Pituitary
Principles of Human Anatomy and Physiology, 11e 26
Feedback
• Secretion of anterior pituitary gland hormones is regulated by hypothalamic regulating hormones and by negative
feedback mechanisms.
Principles of Human Anatomy and Physiology, 11e 27
Negative Feedback Systems
• Decrease in blood levels
• Receptors in hypothalamus & thyroid
• Cells activated to secrete
more TSH or more T3 & T4
• Blood levels increase
11/26/2007
10
Principles of Human Anatomy and Physiology, 11e 28
Human Growth Hormone and
Insulin-like Growth Factors
• Human growth hormone (hGH) is the most plentiful anterior pituitary hormone.
• It acts indirectly on tissues by promoting the synthesis and secretion of small protein hormones called insulin-like
growth factors (IGFs).
– IGFs stimulate general body growth and regulate various
aspects of metabolism.
– One symptom of excess hGH is hyperglycemia.
Principles of Human Anatomy and Physiology, 11e 29
Human Growth Hormone
• Produced by somatotrophs
• target cells synthesize insulinlike growth
– common target cells are liver, skeletal muscle, cartilage and bone
– increases cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins
– stimulate lipolysis in adipose so fatty acids used for ATP
– retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain
Principles of Human Anatomy and Physiology, 11e 30
Regulation of hGH
• Low blood sugar stimulates release of GHRH from hypothalamus
– anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells
• High blood sugar stimulates release of GHIH from hypothalamus
– less hGH from anterior pituitary, glycogen does not breakdown into glucose
11/26/2007
11
Principles of Human Anatomy and Physiology, 11e 31
Thyroid Stimulating Hormone (TSH)
• Hypothalamus regulates thyrotroph cells
• Thyrotroph cells produce TSH
• TSH stimulates the synthesis & secretion of T3 and T4
• Metabolic rate stimulated
Principles of Human Anatomy and Physiology, 11e 32
Follicle Stimulating Hormone (FSH)
• Releasing hormone from hypothalamus controls
gonadotrophs
• Gonadotrophs release
follicle stimulating hormone
• FSH functions
– initiates the formation of follicles within the ovary
– stimulates follicle cells to secrete estrogen
– stimulates sperm production
in testes
Principles of Human Anatomy and Physiology, 11e 33
Luteinizing Hormone (LH)
• Releasing hormones from hypothalamus stimulate gonadotrophs
• Gonadotrophs produce LH
• In females, LH stimulates
– secretion of estrogen
– ovulation of 2nd oocyte from ovary
– formation of corpus luteum
– secretion of progesterone
• In males, LH stimulates the interstitial cells of the testes to secrete testosterone.
11/26/2007
12
Principles of Human Anatomy and Physiology, 11e 34
Prolactin (PRL)
• Prolactin (PRL), together with other hormones, initiates and maintains milk
secretion by the mammary glands.
– Hypothalamus regulates
lactotroph cells
– Lactotrophs produce prolactin
– Under right conditions, prolactin causes milk production
• Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production
Principles of Human Anatomy and Physiology, 11e 35
Adrenocorticotrophic Hormone
• Adrenocorticotrophic hormone(ACTH) controls the production and secretion of hormones called glucocorticoids by the cortex of the adrenal gland.
– Hypothalamus releasing hormones stimulate corticotrophs
– Corticotrophs secrete ACTH & MSH
– ACTH stimulates cells of the adrenal cortex that produce glucocorticoids
Principles of Human Anatomy and Physiology, 11e 36
Melanocyte-Stimulating Hormone
• Melanocyte-stimulating hormone (MSH) increases skin pigmentation although its exact role in humans is
unknown.
– Releasing hormone from hypothalamus increases
MSH release from the anterior pituitary
– Secreted by corticotroph cells
• Function not certain in humans (increase skin pigmentation in frogs )
11/26/2007
13
Principles of Human Anatomy and Physiology, 11e 37
Posterior Pituitary Gland (Neurohypophysis)
• Although the posterior pituitary gland does not synthesize hormones, it does store and release two hormones.
– Hormones made by the hypothalamus and stored in the posterior pituitary are oxytocin (OT) and antidiuretic
hormone (ADH).
– The neural connection between the hypothalamus and
the neurohypophysis is via the hypothalamohypophyseal tract.
Principles of Human Anatomy and Physiology, 11e 38
Posterior Pituitary Gland (Neurohypophysis)
• Does not synthesize hormones
• Consists of axon terminals of hypothalamic neurons
• Neurons release two neurotransmitters into
capillaries
– antidiuretic hormone
– oxytocin
Principles of Human Anatomy and Physiology, 11e 39
Oxytocin
• Two target tissues both involved in neuroendocrine reflexes
• During delivery
– baby’s head stretches cervix
– hormone release enhances uterine muscle contraction
– baby & placenta are delivered
• After delivery
– Oxytocin stimulates contraction of the uterus and ejection (let-down) of milk from the breasts.
• Nursing a baby after delivery stimulates oxytocin release, promoting uterine contractions and the expulsion of the placenta.
• suckling & hearing baby’s cry stimulates milk ejection
11/26/2007
14
Principles of Human Anatomy and Physiology, 11e 40
Oxytocin during Labor
• Stimulation of uterus by baby
• Hormone release from posterior pituitary
• Uterine smooth muscle contracts until birth of baby
• Baby pushed into cervix, increase hormone release
• More muscle contraction occurs
• When baby is born, positive feedback
ceases
Principles of Human Anatomy and Physiology, 11e 41
ADH
• Antidiuretic hormone stimulates water reabsorption by the kidneys and arteriolar constriction.
• The effect of ADH is to decrease urine volume and conserve body water.
• ADH is controlled primarily by osmotic pressure of the blood.
Principles of Human Anatomy and Physiology, 11e 42
Antidiuretic Hormone (ADH)
• Known as vasopressin
• Functions
– decrease urine production
– decrease sweating
– increase BP
11/26/2007
15
Principles of Human Anatomy and Physiology, 11e 43
Regulation of ADH
• Dehydration
– ADH released
• Overhydration
– ADH inhibited
Principles of Human Anatomy and Physiology, 11e 44
THYROID GLAND
• The thyroid gland is located just below the larynx and has right and left lateral lobes.
• Histologically, the thyroid consists of the thyroid follicles composed of follicular cells, which secrete the thyroid
hormones thyroxine (T4) and triiodothyronine (T3) and parafollicular cells, which secrete calcitonin (CT).
Principles of Human Anatomy and Physiology, 11e 45
Thyroid Gland
• On each side of trachea is lobe of thyroid• Weighs 1 oz & has rich blood supply
11/26/2007
16
Principles of Human Anatomy and Physiology, 11e 46
Histology of Thyroid Gland
• Follicle = sac of stored hormone (colloid) surrounded
by follicle cells that produced it
– T3 & T4
• Inactive cells are short
• In between cells called
parafollicular cells
– produce calcitonin
Principles of Human Anatomy and Physiology, 11e 47
Photomicrograph of Thyroid Gland
Principles of Human Anatomy and Physiology, 11e 48
Formation, Storage and Release of Thyroid Hormones
• Thyroid hormones are synthesized from iodine and tyrosine within a large glycoprotein molecule called thyroglobulin
(TGB) and are transported in the blood by plasma proteins, mostly thyroxine-binding globulin (TBG).
• The formation, storage and release steps include:
– iodide trapping
– synthesis of thyroglobulin
– oxidation of iodide
– iodination of tyrosine
– coupling of T1 and T2
– pinocytosis and digestion of colloid
– secretion of thyroid hormones and transport in blood
11/26/2007
17
Principles of Human Anatomy and Physiology, 11e 49
Formation of Thyroid Hormone
• Iodide trapping by follicular cells
• Synthesis of thyroglobulin (TGB)
• Release of TGB into colloid
• Iodination of tyrosine in colloid
• Formation of T3 & T4 by combining T1 and T2 together
• Uptake & digestion of TGB by follicle cells
• Secretion of T3 & T4 into blood
Principles of Human Anatomy and Physiology, 11e 50
Actions of Hormones from
Thyroid Gland
• T3 & T4
– thyroid hormones responsible for our metabolic rate, synthesis
of protein, breakdown of fats, use of glucose for
ATP production
• Calcitonin
– responsible for building of
bone & stops reabsorption of bone (lowers blood
levels of Calcium)
Principles of Human Anatomy and Physiology, 11e 51
Control of T3 & T4 Secretion
• Negative feedback system
• Low blood levels of hormones stimulate hypothalamus
• It stimulates pituitary to
release TSH
• TSH stimulates gland to raise
blood levels
11/26/2007
18
Principles of Human Anatomy and Physiology, 11e 52
PARATHYROID GLANDS
• The parathyroid glands are embedded on the posterior surfaces of the lateral lobes of the thyroid
– principal cells produce parathyroid hormone
– oxyphil cells--function is unknown
• Parathyroid hormone (PTH) regulates the homeostasis of calcium and phosphate
• increase blood calcium level
• decrease blood phosphate level
– increases the number and activity of osteoclasts
– increases the rate of Ca+2 and Mg+2 from reabsorption from urine and inhibits the reabsorption of HPO4
-2 so more is secreted in the urine
– promotes formation of calcitriol, which increases the absorption of Ca+2, Mg+2,and HPO4
-2 from the GI tract
Principles of Human Anatomy and Physiology, 11e 53
Parathyroid
Glands
• 4 pea-sized glands found on back of thyroid gland
Principles of Human Anatomy and Physiology, 11e 54
Histology of Parathyroid Gland
• Principal cells produce parathyroid hormone
(PTH)
• Oxyphil cell function is
unknown
11/26/2007
19
Principles of Human Anatomy and Physiology, 11e 55
Blood Calcium
• Blood calcium level directly controls the secretion of calcitonin and parathyroid hormone via negative feedback
loops that do not involve the pituitary gland.
Principles of Human Anatomy and Physiology, 11e 56
Regulation of Calcium Blood Levels
• High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CT
Principles of Human Anatomy and Physiology, 11e 57
Adrenal Glands
• The adrenal glands are located superior to the kidneys • 3 x 3 x 1 cm in size and weighs 5 grams
• consists of an outer cortex and an inner medulla.
– Cortex produces 3 different types of hormones from 3 zones of cortex
– Medulla produces epinephrine & norepinephrine
11/26/2007
20
Principles of Human Anatomy and Physiology, 11e 58
Adrenal Cortex
• The adrenal cortex is divided into three zones, each of which secretes different hormones.
– The zona glomerulosa (outer zone)
• secretes mineralocorticoids.
– The zona fasciculata (middle zone)
• secretes glucocorticoids.
– The zona reticularis (inner zone)
• secretes androgens.
Principles of Human Anatomy and Physiology, 11e 59
Histology of
Adrenal
Gland
• Cortex
– 3 zones
• Medulla
Principles of Human Anatomy and Physiology, 11e 60
Mineralocorticoids
• 95% of hormonal activity due to aldosterone
• Functions
– increase reabsorption of Na+ with Cl- , bicarbonate and water following it
– promotes excretion of K+ and H+
• Hypersecretion = tumor producing aldosteronism
– high blood pressure caused by retention of Na+ and water in blood
11/26/2007
21
Principles of Human Anatomy and Physiology, 11e 61
Regulation of Aldosterone
Principles of Human Anatomy and Physiology, 11e 62
Glucocorticoids
• 95% of hormonal activity is due to cortisol
• Functions = help regulate metabolism
– increase rate of protein catabolism & lipolysis
– conversion of amino acids to glucose
– stimulate lipolysis
– provide resistance to stress by making nutrients available for ATP production
– raise BP by vasoconstriction
– anti-inflammatory effects reduced
• reduce release of histamine from mast cells
• decrease capillary permeability
• depress phagocytosis
Principles of Human Anatomy and Physiology, 11e 63
Androgens from Zona Reticularis
• Small amount of male hormone produced
– insignificant in males
– may contribute to sex drive in females
– is converted to estrogen in postmenopausal females
11/26/2007
22
Principles of Human Anatomy and Physiology, 11e 64
Adrenal Medulla
• Chromaffin cells receive direct innervation from sympathetic nervous system
– develop from same tissue as postganglionic neurons
• Produce epinephrine & norepinephrine
• Hormones are sympathomimetic
– effects mimic those of sympathetic NS
– cause fight-flight behavior
• Acetylcholine increases hormone secretion by adrenal medulla
Principles of Human Anatomy and Physiology, 11e 65
PANCREATIC ISLETS
• The pancreas is a flattened organ located posterior and slightly inferior to the stomach and can be classified as both
an endocrine and an exocrine gland.
• Histologically, it consists of pancreatic islets or islets of
Langerhans and clusters of cells (acini) (enzyme-producing exocrine cells).
Principles of Human Anatomy and Physiology, 11e 66
Anatomy of Pancreas
• Organ (5 inches) consists of head, body & tail• Cells (99%) in acini produce digestive enzymes
• Endocrine cells in pancreatic islets produce hormones
11/26/2007
23
Principles of Human Anatomy and Physiology, 11e 67
Cell Organization in Pancreas
• Exocrine acinar cells surround a small duct
• Endocrine cells secrete near a capillary
Principles of Human Anatomy and Physiology, 11e 68
Histology of the Pancreas
• 1 to 2 million pancreatic islets
• Contains 4 types of endocrine cells
Principles of Human Anatomy and Physiology, 11e 69
Cell Types in the Pancreatic Islets
• Alpha cells (20%) produce glucagon
• Beta cells (70%) produce insulin
• Delta cells (5%) produce somatostatin
• F cells produce pancreatic polypeptide
11/26/2007
24
Principles of Human Anatomy and Physiology, 11e 70
Regulation
• Regulation of glucagon and insulin secretion is via
negative feedback mechanism.
– Low blood glucose stimulates release of
glucagon
– High blood glucose stimulates secretion of
insulin
• Table summarizes the
hormones produced by the pancreas, their principal actions and control of
secretion.
Principles of Human Anatomy and Physiology, 11e 71
Ovaries and Testes—see lectures on the Male and
Female Reproductive Systems
• Ovaries
– estrogen, progesterone, relaxin & inhibin
– regulate reproductive cycle, maintain pregnancy & prepare mammary glands for lactation
– 2nd sexual characteristics
• Testes
– produce testosterone
– regulate sperm production & 2nd sexual
characteristics
Principles of Human Anatomy and Physiology, 11e 72
Pineal Gland
• Small gland attached to 3rd ventricle of brain
• Consists of pinealocytes & neuroglia
• Melatonin responsible for setting of biological clock
11/26/2007
25
Principles of Human Anatomy and Physiology, 11e 73
Effect of Light on Pineal Gland
• Melatonin secretion producing sleepiness occurs during darkness due to lack of stimulation from sympathetic ganglion
Principles of Human Anatomy and Physiology, 11e 74
Seasonal Affective Disorder and Jet Lag
• Depression that occurs during winter months when day length is short
• Due to overproduction of melatonin
• Therapy
– exposure to several hours per day of artificial light as bright as sunlight
– speeds recovery from jet lag
The End
Principles of Human Anatomy and Physiology, 11e 75