endocrine lecture--edit.ppt

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Principles of Human Anatomy and Physiology, 11e 1

The Endocrine System

Lecture Series


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


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.

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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.


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


Hormone Receptors

• Hormones only affect target cells with specific membrane proteins called receptors

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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)


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


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.

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Circulating & Local Hormones

• Circulating hormones

• Local hormones

– paracrines

– autocrines


Chemical Classes of Hormones

• Lipid-soluble hormones include the steroids and thyroid hormone.

• Water-soluble hormones include the amines--peptides,

proteins and glycoproteins


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

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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


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


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

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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.


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


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.

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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.


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


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• 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


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.


Flow of Blood to

Anterior Pituitary

• Controlling hormones enter blood

• Travel through portal veins

• Enter anterior pituitary at capillaries

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Anterior Pituitary


Feedback

• Secretion of anterior pituitary gland hormones is regulated by hypothalamic regulating hormones and by negative

feedback mechanisms.


Negative Feedback Systems

• Decrease in blood levels

• Receptors in hypothalamus & thyroid

• Cells activated to secrete

more TSH or more T3 & T4

• Blood levels increase

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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.


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


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

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Thyroid Stimulating Hormone (TSH)

• Hypothalamus regulates thyrotroph cells

• Thyrotroph cells produce TSH

• TSH stimulates the synthesis & secretion of T3 and T4

• Metabolic rate stimulated


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


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.

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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


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


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 )

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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.


Posterior Pituitary Gland (Neurohypophysis)

• Does not synthesize hormones

• Consists of axon terminals of hypothalamic neurons

• Neurons release two neurotransmitters into

capillaries

– antidiuretic hormone

– oxytocin


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

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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


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.


Antidiuretic Hormone (ADH)

• Known as vasopressin

• Functions

– decrease urine production

– decrease sweating

– increase BP

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Regulation of ADH

• Dehydration

– ADH released

• Overhydration

– ADH inhibited


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).


Thyroid Gland

• On each side of trachea is lobe of thyroid• Weighs 1 oz & has rich blood supply

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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


Photomicrograph of Thyroid Gland


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

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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


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)


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

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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


Parathyroid

Glands

• 4 pea-sized glands found on back of thyroid gland


Histology of Parathyroid Gland

• Principal cells produce parathyroid hormone

(PTH)

• Oxyphil cell function is

unknown

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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.


Regulation of Calcium Blood Levels

• High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CT


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

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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.


Histology of

Adrenal

Gland

• Cortex

– 3 zones

• Medulla


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

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Regulation of Aldosterone


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


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

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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


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).


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

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Cell Organization in Pancreas

• Exocrine acinar cells surround a small duct

• Endocrine cells secrete near a capillary


Histology of the Pancreas

• 1 to 2 million pancreatic islets

• Contains 4 types of endocrine cells


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

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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.


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


Pineal Gland

• Small gland attached to 3rd ventricle of brain

• Consists of pinealocytes & neuroglia

• Melatonin responsible for setting of biological clock

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Effect of Light on Pineal Gland

• Melatonin secretion producing sleepiness occurs during darkness due to lack of stimulation from sympathetic ganglion


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


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endocrine lecture--edit.ppt