exam 3 mcb 246 ENDOCRINE

ENDOCRINE 1

TRANSPORT AND TARGET

hormone transport to target cell

1. hormone released to interstitial space

2. enters and transported in blood

3. randomly leaves blood and enters interstitial space

4. hormone binds to target cell receptor

how does the endocrine system differ from the nervous system

• transmits hormones through blood

• targets any cell in body with correct receptor

• can be widespread

• longer reaction time

• longer lasting effects (min-weeks)

how is the endocrine system like the nervous system

• control system of body

• release ligands that bind receptors on target cells

endocrine general functions

1. regulate development growth and metabolism

2. maintain blood composition

3. control digestive processes

4. control reproductive processes

where is the endocrine system located

1. major endocrine organs

2. organs/tissues with clusters of endocrine cells

major endocrine function

1. pituitary gland

2. pineal gland

3. thyroid gland

4. adrenal gland

organs/tissues with endocrine cell clusters

1. hypothalamus

2. skin

3. thymus

4. heart

5. liver

6. stomach

7. pancreas

8. small intestine

9. adipose connective tissue

10. kidneys

11. gonads

types of hormone stimulation

hormonal stimulation

humoral stimulation

nervous system stimulation

hormonal stimulation

gland releases hormone when other hormone binds to it

ex TSH and TH

humoral stimulation

gland releases hormone when there is a change in levels of a nutrient or ion in the blood

ex glucose increases so insulin is released

nervous system stimulation

gland releases hormone when neuron stimulates it

ex - sympathetic division stimulated so nor- epi- nephrine is secreted

hormone types “classes”

circulating hormones

local hormones

circulating hormone types

steroid hormones

biogenic amines

proteins

steroid hormones

lipid soluble

synthesized from cholesterol

biogenic amines

water soluble except for TH

modified amino acids

protein hormones

water soluble

chains of amino acids

most hormones fall into what category

protein hormones

which hormones are steroid hormones

estrogen

progesterone

testosterone

cortisol

aldosterone

calcitrol (sterol)

which hormones are biogenic amines

catecholamines

thyroid hormone

melatonin

which hormones are protein hormones

ADH, insulin, glucagon, GH, EPO

local hormones

bind autocrine or paracrine

local hormone types

eicosanoids

eicosanoids are

formed from fatty acids within the phospholipid bilayer of membrane

synthesized through enzymatic cascade

eicosanoid subtypes

thromboxanes

prostaglandins

leukotrienes

prostaglandins

type of eicosanoid that is involves in stimulation of pain and inflammatory response

eicosanoid subtype formation

phospholipase A2 removes arachidonic acid from phospholipid

other enzyme converts arachidonic acid to eicosanoid subtype

lipid soluble hormone transport in blood

requires carrier proteins as they do not readily dissolve in blood

carrier proteins

water soluble proteins made by liver

protect hormones from early destruction

bound vs free hormones

most hormones are bound (~90%)

unbound hormones are the only ones that can exit blood and bind to target

water soluble hormone transport in blood

travel freely through blood

may use carriers to prolong biological half life

hormone concentration depends on

hormone release and elimination

hormone elimination occurs by

enzymatic degradation in liver cells

removal from blood by kidney excretion

removal from blood by target cell uptake

biological half life

time it takes to reduce concentration hormone to half its original concentration dependent on how efficiently hormone eliminated

water soluble generally shorter while lipid soluble longer due to carrier protection

characteristics of lipid hormones that allow intracellular receptor binding

• Can diffuse across target cell membrane

• Such hormones are small, nonpolar, and lipophilic

• Their receptors are in the cytosol or nucleus

binding steps of lipid soluble hormone

1. unbound hormone moves through plasma membrane by simple diffusion binds with intracellular hormone receptor within the cytosol of nucleus to form hormone-receptor-complex

2. HRC binds with a DNA sequence called the hormone-response-element

3. HRC to HRE binding stimulates mRNA synthesis

4. mRNA exits nucleus is translated by ribosome in the cytosol and a new protein is synthesized

water soluble hormone characteristics that prevent intracellular receptor binding

• Bind to cell-surface receptors

• Such hormones are polar and can’t diffuse through membrane

binding steps of water soluble hormone to cell surface receptors

1. hormone (first messenger) binds to receptor on plasma membrane induces shape change, activating receptor

2. G protein with GDP binds to activated receptor

3. GDP is bumped off and GTP binds to G protein activating it

4. activated G protein with GTP is released from receptor - 2 different pathways can then be undertaken

G protein and adenylate cyclase

1. activated G protein binds to and activates adenylate cyclase

2. adenylate cyclase converts ATP to cAMP

3. cAMP (second messenger) activates protein kinase A

4. protein kinase A phosphorylates other molecules (inhibiting/activating)

G protein and phospholipase C

1. activated G protein activates phospholipase C

2. phospholipase C splits PIP2 into 2 second messengers: DAG and IP3

3. DAG (second messenger) activates protein kinase C a phosphorylating enzyme

4. IP3 (second messenger) increases calcium in cytosol by stimulating its release from ER

5. Ca (third messenger) activates protein kinase enzymes or alters activity of ion channels

different results possible through different signal transduction pathways

1. activation / inhibition enzymatic pathways

2. growth through cellular division

3. release cellular secretions

4. changes in membrane permeability

5. muscle contraction / relaxation

benefits of intracellular enzyme cascade

1. signal is amplified at each enzymatic step

2. few hormone molecules can change many molecules within the cell

3. many spots to regulate pathway activities (cells can quickly inactivate intermediate)

degree of cell response varies with

• number receptors for hormone

• simultaneous response to other hormones

upregulation hormone receptors

• increase of receptor number on cell

• increases sensitivity to hormone

• occurs with low concentrations of hormone in blood, developmental changes, cell cycle, cell activity

downregulation hormone receptors

• decrease of receptor number on cell

• decreases sensitivity to hormone

• occurs with high concentrations of hormone in blood, developmental changes, cell cycle, cell activity

synergistic hormone interactions

• One hormone reinforces activity of another hormone

• For example, estrogen and progesterone effects on a target cell

permissive hormone interactions

• One hormone requires activity of another hormone

• For example, oxytocin’s milk ejection effect requires prolactin’s milk generating effect

antagonistic hormone interactions

• One hormone opposes activity of another hormone

• For example, glucagon increases blood glucose while insulin lowers it

ENDOCRINE 2

HYPOTHALAMUS AND PITUITARY

hypothalamus

controls pituitary and other organs

SUPRAOPTIC NUCLEUS

PARAVENTRICULAR NUCLEUS

infundibulum

connects hypothalamus and pituitary

HYPOTHALAMO-HYPOPHYSEAL TRACT

HYPOPHYSEAL PORTAL VEINS

pituitary

hypophysis

inferior to hypothalamus in sella turcica of sphenoid bone, pea sized

connects to hypothalamus by infundibulum

partitioned into anterior and posterior

Posterior pituitary

smaller neural part

hypothalamic neurons project through infundibulum and secrete hormones into posterior pituitary

antidiuretic hormone ADH

SYNTHESIZED: neurosecretory cells in supraoptic nucleus in hypothalamus

STORED: PP

RELEASED: PP

FUNCTIONS: decrease urine production, increase thirst, vasoconstrict

oxytocin

SYNTHESIZED - neurosecretory cells in paraventricular nucleus of hypothalamus
STORED - posterior pituitary
RELEASED - posterior pituitary
FUNCTIONS - uterine contractions, milk ejection, emotional bonding

releasing hormones (RHs)

SYNTHESIZED - hypothalamus
RELEASED - hypothalamus
FUNCTIONS - increase secretions of AP hormones

RHs include

Thyrotropin-releasing hormone (TRH)

Corticotropin-releasing hormone (CRH)

Gonadotropin-releasing hormone (GnRH)

Prolactin-releasing hormone (PRH)

Growth hormone–releasing hormone (GHRH)

inhibiting hormones IHs

SYNTHESIZED - hypothalamus
RELEASED - hypothalamus
FUNCTIONS - decrease secretions AP hormones

IHs include

Growth hormone–inhibiting hormone (GIH)

Prolactin-inhibiting hormone (PIH)

Thyroid stimulating hormone TSH

SYNTHESIZED - AP
RELEASED - AP triggered by TRH
FUNCTIONS - release of TH from thyroid gland

prolactin PRL

SYNTHESIZED - AP
RELEASED - AP triggered by PRH or inhibited by PIH
FUNCTIONS - milk production, mammary gland growth

adrenocorticotropic hormone ACTH corticotropin

SYNTHESIZED - AP
RELEASED - AP triggered by CRH
FUNCTIONS - release of corticosteroids by adrenal cortex

gonadotropins - Follicle Stimulating Hormone FSH, Luteinizing Hormone LH

SYNTHESIZED - AP
RELEASED - AP triggered by GnRH
FUNCTIONS

• in females regulate ovarian development and secretion of estrogen and progesterone

• in males regulate sperm development and secretion testosterone

Growth Hormone GH

SYNTHESIZED - AP
RELEASED - AP triggered by GHRH
FUNCTIONS - cause liver to secrete IGF-1 and -2, act synergistically to cause cell growth and division

tropic hormones

stimulate glands to release their hormones

all AP hormones except prolactin

growth hormone regulation steps

1. Stimulus: Variables that influence the release of GHRH from the hypothalamus.

2. Receptor: The hypothalamus responds to various stimuli.

3. Control Center: The hypothalamus releases growth hormone-releasing hormone (GHRH) into the hypothalamo-hypophyseal portal system.

4. In response to GHRH, the anterior pituitary releases growth hormone (GH).

5. GH stimulates hepatocytes to release insulin-like growth factors (IGFs) into the blood.

6. Effectors: Effectors respond to GH and/or IGFs in organ-specific manner.

7. Net Effect: Stimulates growth; nutrient release into blood.

8. Negative Feedback: Increased GH and IGF levels inhibit GHRH release; increased GH levels inhibit further GH release.

stimuli regulating release of GHRH

• A person’s age: GHRH and GH is highest in children and adolescents

• Time of day: peak GHRH and GH occurs at night

• Nutrient levels: increase in nutrient levels stimulates GHRH and GH release

• Stress and exercise: increase release of GHRH and GH (although severe or chronic stress can decrease GH)

Effects of GH

1. Stimulates release of IGFs from liver

• similar functions as GH but longer half-life

• All cells have receptors for GH, IGFs, or both

2. Hormone stimulates increased protein synthesis, cell division, cell differentiation

3. stimulates release of nutrients from storage

GH stimulates these metabolic processes

• Glycogenolysis (breakdown of glycogen into glucose)

• Gluconeogenesis (conversion of nutrients to glucose)

• Lipolysis (breakdown of triglycerides)

GH inhibits these metabolic processes

• Glycogenesis (synthesis of glycogen)

• Lipogenesis (formation of triglycerides)

ENDOCRINE 3

THYROID AND ADRENAL GLAND

anatomy of thyroid

inferior to cartilage, anterior to trachea

left and right lobes connected by isthmus

richly vascularized

cells of thyroid (follicles)

follicular cells

parafollicular cells

follicular cells

cuboidal epithelial cells

surround lumen that houses colloid (viscous protein rich fluid)

synthesize thyroglobulin TGB and TH

Parafollicular cells

cells between follicles

make calcitonin

formation thyroid hormone

IN FOLLICULAR CELL

1. iodine ion uptake - moves from blood across 2 membranes (active transport then facilitated diffusion) into follicular lumen

2. A) Iodine molecule formation - 2 I are joined to form I2 at plasma membrane of follicular cell

2. B) Thyroglobulin synthesis - thyroglobulin protein molecules synth in rough ER released into colloid by exocytosis

IN COLLOID

3. A) tyrosine converted to diiodotyrosine within thyroglobulin molecule - thyroid peroxidase enzyme attaches 1 or 2 iodine to tyrosine making monoiodotyrosine or diiodotyrosine

3. B) pre-T3 and -T4 formation - mono and diiodotyrosine attach to each other to form pre-T3 and -T4

IN FOLLICULAR CELL

4. endocytosis - pre-T3 and T4 move into cell by endocytosis

5. release T3 and T4 from thyroglobulin - vesicles with pre -T3 -T4 and thyroglobulin attach to lysosome, lysosomal enzyme cleaves: T3 or T4 formed

6. Release T3 and T4 into blood - move into blood by transport protein

T3 and T4 collectively are

thyroid hormone

T3 and T4 relative concentrations

more T4 is released than T3, T3 is the more active form

• cells often convert T4 to T3

T3 full name

triiodothyronine

T4 full name

tetraiodothyronine

regulation of thyroid hormone release

hypothalamus monitors stimuli - releases TRH - stimulates AP to release TSH - stimulates thyroid to release TH

regulated by negative feedback

stimuli regulating TRH release

• changes in blood levels TH

• genetics, body changes, environmental factors (vit D deficiency)

TH effects

INCREASE METABOLIC RATE, PROTEIN SYNTESIS, RELEASE NUTRIENTS INTO BLOOD

1. stimulate Na-K pumps in neurons (calorigenic)

2. stimulate increase in aa and glucose uptake

3. increase in number respiration enzymes in mitochondria

4. foster energy ATP production - stimulates hepatocytes to increase blood glucose, increases glycogenolysis and gluconeogenesis, decreases glycogenesis

5. stimulates adipose to increase blood glycerol and fatty acids - increases lipolysis decreases lipogenesis - save glucose for brain

6. increases respiration rate - meet increased O2 demands

7. increases HR and force contraction - increases blood flow, deliver more nutrients and O2, increases receptors for epinephrine and norepinephrine on heart

glucose sparing effect

organs save glucose for use by brain when blood glucose decreases

calcitonin synthesis and release

stimulated by high blood Ca or stress from exercise

synthesized and released from parafollicular cells of thyroid gland

functions of calcitonin

decreases blood Ca levels by

• inhibiting osteoclast activity

• stimulating kidneys to increase excretion Ca in urine

most significant effects in bones of growing children

adrenal gland anatomy

superior surface of kidneys

retroperitoneal, embedded in fat and fascia

regions of the adrenal gland

adrenal medulla

adrenal cortex - zona glomerulosa, fasciculata, reticularis

Adrenal medulla

inner core of gland, red brown color from vascularization

releases epinephrine and norepinephrine with sympathetic stimulation

Adrenal Cortex

synthesizes more than 25 corticosteroids

yellow due to lipids in cells

zona glomerulosa

outer thin layer

mineralocorticoids - aldosterone

mineralocorticoids

regulate electrolyte levels

aldosterone

fosters Na retention and K secretion

zona fasciculata

large middle layer

glucocorticoids - cortisol

glucocorticoids

regulate blood sugar

cortisol

increases blood sugar

zona reticularis

inner thin layer

adrenal androgens

adrenal androgens

sex hormones made by adrenals

in lesser quantities than from testes

regulation cortisol release

monitored by hypothalamus - releases CRH - AP releases ACTH - stimulates fasciculata to release glucocorticoids (cortisol)

ACTH and CRH negative feedback loop

stimuli regulating CRH release

negative feedback by cortisol increase

time of day - increase night, peak early morning

stress - increases release