The Endocrine System

Endocrine System

• Function:• Regulates• Coordinates• Integrates• Works cooperatively with the nervous system• No ducts: • Reactions not immediate -last longer than

N.S. responses

Hormones

• Substances secreted by cells that regulate the activity of another tissue or organ• Most produced by glands• Some produced by clusters of cells• Some produced by neurons (neurohormones)

Hormones

• Types of Hormones• Amino Acid Derivatives• Simple amines, thyroxin, peptides and proteins • Examples:• Thyroid hormones, epinephrine and NE, insulin,

glucagon

• Most hormones this type

Hormones

• Types of hormones• Steroid hormones• Derived from cholesterol• Includes gonadal hormones (sex hormones) and

adrenal hormones (cortex only)• Examples:• Progesterone, testosterone, cortisol,

aldosterone

Hormones

• Types of hormones• Eicosanoids• Are paracrine hormones (local hormone = produced

by cells and released to effect cells in the same area)• Examples:• Prostaglandins, leukotrines

Intracellular Receptors

Receptors

• On the target cell -bind hormone • Determine the effect the hormone will have on the

target cell• Binding may cause:• Change in membrane permeability or potential• Synthesis of substances such as proteins or enzymes• Activation or deactivation of enzymes• Secretion of substances• Stimulation of mitosis

Hormone Actions

• Alter the activity of target cells• Decrease or increase cellular activity in target cells• Only affect cells with receptors for that hormone

Hormone action: What happens when a hormone binds with a receptor?

1. Channels

2. 2nd messenger

3. Genes

HORMONE ACTION

Where are the receptors?1. On the cell membrane (AA hormones)

intracellular second messenger2. In the nucleus (steroid hormones & thyroxine)

direct gene activation

HORMONE ACTION- Second Messenger

Intracellular second messenger• Hormone• Receptor• G protein• Adenylate cyclase system• Cyclic AMP• Protein kinases

Hormone Mechanisms

• Second Messengers• Hormone binds to a

receptor on plasma membrane • Series of reactions

initiated within the cell• Example:• Cyclic AMP

Second Messengers

• Cyclic AMP (cAMP)• Formed from ATP when a

hormone binds to receptor • Hormone/receptor binding• ‘G’ protein activates or

inhibits adenyl cyclase• ATP converted to cAMP• May activate protein kinases• Initiates cascade of enzymes

within the cell• Effect depends upon target

cell

Second Messenger System

Second Messengers

• PIP Mechanism• PIP2 split into

diacylglycerol and IP3

• Both act as second messengers• IP3 triggers the release

of calcium from the ER• Ca2+ acts as a third

messenger • Diacylglycerol may

activate protein kinases

Second messenger system

Direct Activation of Genes

• Steroid hormones can pass through the plasma membrane• Bind to receptors inside cell• Hormone/receptor binding stimulates genes on the DNA to

begin protein production

Gene Activation

Hormone Regulation

•Nervous System• Ultimate control of hormone mechanisms

belongs to the nervous system• Mainly hypothalamus and sympathetic

nervous system

Endocrine Gland Stimuli

Hormone Regulation

• Stimulation or inhibition of endocrine glands comes from THREE sources:

Other hormones

Humoral stimuli

Neural stimuli

Hormone Regulation• Hormonal Regulation (by other

Hormones)• Hormones may stimulate or

inhibit the release of other hormones• Hypothalamus-• Regulates anterior

pituitary gland• Pituitary hormones-• Stimulate release of

hormones from other glands

Hormone Regulation

• Regulation by Humoral Stimuli• Changing ion or nutrient levels

in the blood may inhibit or stimulate the release of hormones

• Example:• Low blood calcium (Ca2+)• PTH released from the

parathyroid glands• Ca2+ released from bone• Increase in blood Ca2+

Hormone Regulation

• Regulation by Neural Stimuli• Nerve impulses may

stimulate the release of hormones

• Example:• Sympathetic neurons

stimulate release of epinephrine and norepinephrine from the adrenal medulla

Feedback Mechanisms

• Negative Feedback System• Rising hormone or ion levels

inhibit further hormone release from the gland

• Positive Feedback System• Rising hormone levels cause

an increase in the hormone being secreted

Hypo or Hypersecretion• May result in a disorder• Examples:

• Diabetes

• Grave’s disease

• Addison’s disease

• Cushing’s disease

Major Endocrine Glands

• Pituitary Gland (Hypophysis)• Posterior lobe

(Neurohypophysis)• Releases 2 hormones

produced in the hypothalamus

anterior lobe

posterior lobe

Posterior Pituitary Gland

• Posterior Lobe• Derived from

hypothalamus• Posterior lobe +

infundibulum = neurohypophysis• Neuron axons to pituitary

= hypothalamic hypophyseal tract

hypothalamic hypophyseal tract

Posterior Pituitary Gland

• Two hormones released here• Both produced in nuclei of the

hypothalamus• Both secreted into capillaries in

posterior pituitary for distribution to the body

Oxytocin & ADH

Hypothalamus

SON/PVN – produce ADH & oxytocin

Released from posterior pituitary

Pituitary

Posterior lobe:• Pituicytes

• ADH

• Oxytocin

Posterior Pituitary Gland• Supraoptic Nucleus• ADH (Vasopressin)• Stimulates increased

reabsorption of water by kidney tubules

• Decreases urine volume• Increases blood volume• React to Osmoreceptors

ADH & oxytocin

Paraventricular Nucleus Oxytocin Uterine contractions Milk release (Contraction

of mammary gland smooth muscle

Supraoptic nuclei

Paraventricular nuclei

Ventral Hypothalamus

Releasing and inhibiting hormones Thru portal system Target = anterior pituitary

Anterior Pituitary Gland

• Hypophyseal Portal System

primary capillary plexus

neurons in ventral hypothalamus

hypophyseal portal veins

secondary capillary plexus

secretory cells

Anterior Pituitary Gland

• Anterior Lobe = Adenohypophysis• Derived from roof of mouth• Produces hormones• Release of hormones is controlled

by hormones from neurons of the ventral hypothalamus = releasing or inhibiting hormones

anterior lobe

Ventral hypothalamu

s

Pituitary (Hypophysis) Location and relationships Densely packed cells (anterior)

Anterior lobe:• TSH

• ACTH

• FSH

• LH• GnRH

• Growth h.

• Prolactin

• MSH

Anterior Pituitary Gland

• The following four anterior pituitary hormones are tropic hormones

• Tropic Hormones:

TSH

ACTH

FSH

LH

Tropic Hormones• Hormones Secreted

• Thyroid Stimulating Hormone (TSH)• Stimulates production and release of thyroid hormones

by the thyroid gland

• Release stimulated by TRH• Inhibited by rising blood levels of thyroid hormone

Tropic Hormones

• Hormones Secreted• Adrenocorticotropic Hormone (ACTH or Corticotropin)• Stimulates secretion of corticosteroid hormones (esp.

cortisol) from the adrenal cortex• Release stimulated by CRH, fever, hypoglycemia and

stress• Inhibited by rising cortisol levels

Tropic Hormones

• Hormones Secreted• Follicle Stimulating Hormone (FSH)• Not present until puberty• Stimulates gamete production and maturation in both males

and females• Release stimulated by GnRH• Inhibited by rising gonadal hormones

Anterior Pituitary Gland

• Hormones Secreted

• Luteinizing Hormone (LH)

• Promotes production of gonadal hormones

• Controlled by the same hormones as FSH

• Triggers ovulation in females

Non-tropic Hormones

• Hormones Secreted• Growth Hormone (GH) or Somatotropin• Produced in response to growth hormone releasing

hormone (GHRH from hypothalamus)• Also secreted in response to hypoglycemia or decreased

blood GH or Increased amino acid levels• Inhibited by GHIH (somatostatin from hypothalamus)• Stimulates cell growth and division in most cells (esp.

bone and muscle)• Mobilizes fat to conserve glucose• Hyposecretion results in pituitary dwarfism• Hypersecretion results in gigantism or acromegaly

Non-tropic Hormones

Hormones Secreted Prolactin (PRL)

Release stimulated by PRH

Inhibited by PIH (dopamine)

Both are influenced by estrogen

Stimulates milk production by breasts

Thyroid Gland - Anatomy

The Thyroid Gland

• Two lateral lobes• Composed of follicles• Cuboidal follicle cells produce thyroglobulin• Thyroglobulin stored in lumen of follicle• Iodine attaches• Molecule is split into T3 and T4 (mostly T4)

• Hormones enter circulation, more T3 formed

thyroid gland

Thyroid Gland - histology

Follicular cells follicles colloidthyroglobulin

T3 – triiodothyronine

T4 – thyroxine

Parafollicular cellsCalcitonin

Thyroid Gland - hormones

Follicular cells thyroglobulin

T3 – triiodothyronineT4 – thyroxine

• + BMR (glucose oxidation)• maintains bp• tissue growth & development

Parafollicular cellsCalcitonin

• decreases blood calcium• + osteoblasts

Thyroid Gland – T3/T4 production

Follicles – colloid, follicular cells Cells make thyroglobulin Thyroglobulin moves into follicle Iodine pumped into follicle Iodine used to make subunits

• 1 OR 2 IODINE

Subunits moved into follicle cells Subunits join to make T3 or T4 T3/T4 released from follicle cells

Thyroid Hormone Production

Thyroid Hormone

• T4 converted to T3 once in tissues• Secreted in response to TSH• Inhibited by rising blood thyroid hormone levels• Effects:• Increases metabolic rate• Increases heat production• Promotes protein synthesis and enhances the affect of GH• Promotes uptake of glucose by cells• Promotes lipid metabolism• Speeds up actions of nervous system

Thyroid Hormone

• Hyposecretion• Can result in cretinism

in children

• Myxedema in adults

• Hypersecretion• Grave’s Disease

Thyroglobulin

Thyroid Gland - pathology

Myxedema – adult hypothyroid

Goiter – enlarged thyroid due to lack of iodine

Cretinism – infantile hypothyroid

Grave’s disease – hyperthyroid exophthalmos

Calcitonin

• Secreted by parafollicular or C cells by the thyroid• Released in response

high blood calcium• Stimulates uptake of

calcium by bone

parafollicular cells

Parathyroid Glands• 4 to 8 on posterior thyroid

gland• Secrete Parathyroid Hormone

(PTH)• Secreted in response to low

blood calcium• Stimulates bone resorption• Released calcium enters blood• Increases absorption of

calcium by intestines and reabsorption by kidneys

parathyroid glands

Parathyroid Hormone

• Hypersecretion• Depletes calcium from bones• Depresses nervous system

activity• Skeletal muscle weakness

• Hyposecretion• Over excitability of neurons• Muscle spasms• Convulsions

Chief cells

Adrenal (Suprarenal) Glands

• Two glands--one on top of each kidney• Outer cortex, inner medulla• Cortex• Produces over 2 dozen

corticosteroids from cholesterol• Increased hormone output in

response to ACTH or stress

adrenal gland

cortex

medulla

Adrenal Cortex

• Three Regions:Zona Glomerulosa• Outer region• Production of

mineralocorticoids (aldosterone)• Regulation of

electrolyte & fluid balance

Aldosterone

• 95% of mineralocorticoids• Sodium reabsorption (and water) by kidney

tubules• Increases blood volume and pressure• Stimulated by angiotensin• Renin secreted by kidneys• Activates angiotensin hormones in blood• Stimulates release of aldosterone

• Inhibited by Atrial Natriuretic Factor (ANF)• Secreted by heart cells when B.P. rises• Blocks secretion of renin and aldosterone

Adrenal Cortex

Zona Fasciculata• Middle region• Secretes glucocorticoids

(cortisol)

• Cortisol• Released in response to ACTH• Inhibited by increased cortisol• Promotes gluconeogenesis

(production of glucose from non-carbohydrate sources)

• Causes a rise in B.P.• Anti-inflammatory if given in

higher doses

Cortisol• Hypersecretion• Cushing’s Syndrome• Depressed bone and cartilage formation• Depressed inflammatory response and immune

system• Edema, hypertension, loss of muscle and bone,

‘moon face’• Hyposecretion• Addison’s disease• Drop in blood plasma volume• Inability to cope with stress or regulate blood

sugar levels• Increased skin pigmentation

Adrenal Cortex

Zona Reticularis• Inner region• Produces

glucocorticoids & gonadocorticoids (androgens and estrogen)

ADRENAL MEDULLA

• Chromaffin Cells• Secrete epinephrine

and norepinephrine (Catecholamines) • Release stimulated by

sympathetic neurons• Prolongs the fight or

flight response

The Pancreas• Mixed endocrine and

exocrine function

• Acinar Cells• Secrete digestive

enzymes into small intestine

• Islets of Langerhans• Contain alpha cells • Glucagon

• Contain beta cells• Insulin

Pancreas

endocrine and exocrine Islets of Langerhans Cell Types:

Alpha Glucagon Increases blood sugar

Beta Insulin Decreases blood sugar

Delta Somatostatin Inhibit glucagon/insulin releaseInhibit digestive tract activity

PP Pancreatic Polypeptide

Regulates exocrine functionInhibits bile release

Insulin

• Stimulated by high blood sugar

• Inhibited by decrease in blood sugar or somatostatin (GHIH)

• Lowers blood sugar• Enhances glucose

transport into cells (esp. muscle)

• Stimulates glycogen formation

• Promotes conversion of glucose to fat

• Stimulates protein synthesis in muscle

Islet of Langerhans

Glucagon

• Released in response to low blood sugar

• Mobilizes fatty acids, glucose and amino acids from storage

• Promotes release of fat from adipose tissue

• Promotes:• Gluconeogenesis (production

of glucose from non-carb. sources)

• Glycogenolysis (breakdown of glycogen into glucose)

• Raises blood sugar levels

Diabetes

• Diabetes Insipidus• Caused by ADH deficiency • Large quantities of urine• Dehydration • No blood sugar accumulation

• Diabetes Mellitus• Results from Hyposecretion of insulin or hypoactivity of insulin

Diabetes• Diabetes Mellitus• Two types:• Type 1 (Juvenile Onset)• Usually before age 20• Decreased amount of beta cells in pancreas• Possibly autoimmune cause• Long term vascular and neural problems

• Type 2 (Adult Onset)• Insulin is produced but receptors are resistant to it• Family tendencies• Influenced by weight, diet and exercise

Diabetes

• Lack of insulin or response to it• Inability of glucose to enter body cells• High blood sugar• Fat stores are mobilized for fuel• Blood sugar and fatty acid levels rise higher• Ketone bodies build up from breakdown of fatty acids• Ketosis or acidosis results (lowered blood pH)• Crisis, coma or death

Diabetes

• Symptoms• Polyuria• Large urine output

• Polydipsia• Excessive thirst

• Polyphagia• Excessive hunger caused by the inability to use glucose

as an energy source

The Pineal Gland• Secretes melatonin• May affect responses to

light cycles• May inhibit gonad

activity in humans until puberty

“brain sand”

The Thymus Gland

• Shrinks with age• Produces thymopoietin and

thymosin• Aids in development of the

immune response (development of T- lymphocytes)

THE GONADS• Produce gametes and reproductive hormones• Testosterone in males• Maturation of reproductive organs• Secondary sex characteristics• Sex drive

• Estrogens and progesterone in females• Estrogens cause maturation of reproductive organs and

appearance of secondary sex characteristics• With progesterone, promote breast development and

cyclic changes in uterine lining