CH. 16 The Endocrine System

endocrine system releases

hormones, that are then transported thru blood.

response times for hormones

slower, but last longer than nervous system responses

endocrinology

the study of hormones and endocrine organs

endocrine system controls and integrates

• reproduction

• growth and development

• maintenance of electrolyte, water, and nutrient balance of blood

• regulation of cellular metabolism and energy balance

• mobilization of body defenses

exocrine glands

produce nonhormonal substances (ex. saliva, sweat)

• have ducts to carry secretion to membrane surface

endocrine glands

pituitary, thyroid, parathyroid, adrenal, and pineal glands

what do endocrine hormones produce

• hormones, but they lack ducts

• circulated by blood to target tissues

hypothalamus is

neuroendocrine organ

what organs have both exocrine and endocrine functions

• pancreas

• gonads

• placenta

hormones

long-distance chemical signals, travel in blood or lymph

autocrines

chemicals that exert effects on the same cells that secrete them

paracrines

locally acting chemicals that affect cells other than those that secrete them.

• diffuse through ECF to neighboring tissues

two main classes of hormones

• amino acid-based hormones

• steroids

amino acid-based hormones

• amino acid derivatives

• peptides

• proteins

steroids

• synthesized from cholesterol

• gonadal and adrenocortical hormones

hormone action on target cells may be to

• alter plasma membrane permeability and/or membrane potential by opening or closing ion channels

• stimulate synthesis of enzymes or other proteins

• activate or deactivate enzymes

• induce secretory activity

• stimulate mitosis

water-soluble hormones

all amino acid-based hormones EXCEPT thyroid hormone

• act on plasma membrane receptors

• act via 2nd messenger (signal transduction)

• CANNOT ENTER CELL

• receptor types: G-protein linked, enzyme-linked, and ion channel-linked

lipid-soluble hormones

steroid and thyroid hormones

• act on intracellular receptors that DIRECTLY activate genes

• NO 2ND MESSENGERS

• CAN ENTER CELL

two main second-messenger systems for amino acid-based hormones

• cyclic AMP (uses one 2nd messenger)

• PIP2 calcium (uses two 2nd messengers)

cyclic AMP (cAMP)

1. hormone (first messenger) binds to receptor

2. receptor activates a G protein

3. G protein activates or inhibits effector enzyme ADENYLATE CYCLASE

4. Adenylate cyclase then converts ATP TO cAMP (second messenger)

5. cAMP activates PROTEIN KINASES that phosphorylate (add a phosphate) other proteins

6. hormone floats away, or phosphodiesterase (PDE) converts cAMP back to AMP

PIP2-calcium signalling mechanism

• hormone-activated G protein activates a different effector enzyme PHOSPHOLIPASE C

• activated phospholipase C splits membrane protein, PIP2, into two second messengers

-diacylglycerol (DAG) activates protein kinases

-inositol trisphosphate (IP3) causes CA2+ release from intracellular storage sites (DAG and IP3 are first set of second messengers)

• calcium ions act as another second messenger

-CA2+ alters enzyme activity and channels, or binds to regulatory protein CALMODULIN

-calcium-bound calmodulin activates enzymes that amplify cellular response

what are the amino acid-based hormones (water soluble)

from ant pit: TSH, LH, FSH, GH, ACTH, PRL

from post pit: ADH, oxytocin

all pituitary, hypothalamus, thymus, thyroid (functionally a lipid), heart, GIT, pancreas hormones

what are the sterioids (lipid based)

gonads: testosterone, estrogen, progesterone

adrenal cortex: adrenocortical hormones (mineralcorticoids, glucorticoids, gonadocorticoids)

What do PDE blockers do?

keeps the process going much longer, often have high mortality rates

what other hormones work without second messenger system

insulin receptor

• amino acid-based in structure (water soluble), but does NOT USED G PROTEIN COUPLED RECEPTOR

• works without a second messenger system

• insulin receptor in cell membrane (tyrosine kinase) that can phosphorylate something, then activating the downstream signalling

• insulin acts in opposite of glucagon, tells the cell to stop release glucose (bring glucose inside instead) also does protein and fat synthesis (food is used to build proteins and any extra sugar is stored as fat)

where do water soluble hormones come from

the brain

where do lipid soluble hormones come from

gonads and adrenal cortex

what hormone acts like a lipid soluble hormone

thyroid hormone (can go straight into plasma membrane and to target cell)

what do steroids look like

4 interlocking ring structure

lipid soluble hormone activation process

• receptor hormone complex enters nucleus and binds to DNA

• initiates transcription to produce mRNA

• mRNA is then translated into specific protein for various functions (metabolic activities, structural purposes, etc)

water soluble hormones affect

proteins that were already made, can cause proteins to activate/deactivate, secretion, or opening/closing ion channels

• most use 2nd messenger systems except insulin

lipid soluble hormones and thyroid hormone

go straight into the nucleus and determine what protein is made

thyroid hormone

• lipid soluble

• amino acid-based (acts like water soluble)

blood levels of hormones are controlled by

negative feedback mechanisms

hormone release is triggered by

• endocrine gland stimuli

• nervous system modulation

what are the forms of stimuli percieved by the endocrine glands

• humoral stimulus

• neural stimulus

• hormonal stimulus

humoral stimulus

triggered by something in the blood

• ex. low Ca2+ in blood causes parathyroid glands to release PTH goes to bones, activates osteoclasts that digest bones to release calcium into the blood, tell kidneys to hold onto calcium.

neural stimulus

the nervous system triggers a stimulus

• ex. sympathetic fibers tell adrenal medulla to release epinephrine and norepinephrine

hormonal stimulus

hormones signal when other hormones need to be released

• ex. hypothalamus makes TRH which then triggers the release of TSH, which causes the release of thyroid hormone

• ex. adrenal cortex CRH > ACTH > hormones released from adrenal cortex

• ex. gonads GNRH > causes the release of FSH and LH > goes to the gonads and causes release of testosterone or estrogens

target cells must have

specific receptors to which hormone binds.

• ex. ACTH receptors are found only on certain cells of the adrenal cortex, but thyroxin receptors are found on nearly all areas of the body (bc it needs to maintain cell metabolism, as ACTH just needs to go to the adrenal cortex)

target cell activation (biological response) depends on what factors

1. blood levels of hormone (concentration)- if levels of hormone are low, response is low.

2. relative number of receptors on target cell- if hormone can’t bind to a receptor, it does not respond

3. affinity (strength) of binding between receptor and hormone- if affinity is low, effect of response is low

up-regulation

in response to low hormone levels:

• target cells can upregulate gene expression encoding receptors to increase the number of receptors,

• ex. thyroid hormone activity is low, cells can upregulate gene expression to make more hormone absorbed.

• this is a compensatory mechanism to increase the sensitivity of the cell to the hormone in low production

down-regulation

in response to high hormone levels:

• ex. thyroid hormone activity is high, cells can down-regulate and desensitize to the hormone, and overall lower the amount of receptors, because it doesn’t need to respond to all of it.

• a compensatory mechanism to decrease sensitivity to high hormone levels

hormones circulate in blood are either

free or bound

• steroids and thyroid hormone are attached to plasma proteins, all others circulate without carriers

• free hormones are usually water soluble and do not need carriers.

• bound hormones need to be bound to something to help get it to its target. usually steroids and lipid soluble thyroid hormone

concentration of circulating hormone reflects

1. rate of release

2. speed at which it is inactivated and removed from body (cleared by liver or kidneys

hormones have different response times

• some responses are immediate

• some, especially steroid, can take hours to days

• some are inactive until they enter target cells

hormones can be removed from blood by

• degrading enzymes

• kidneys- filter out water soluble hormones (faster)

• liver- clear lipid soluble hormones out (slower)

half-life

time required for level or hormone in blood level to decrease by half

• varies anywhere from fraction of a minute to a week, depending on the hormone

half-life, onset, and duration of hormone activity are dependent on

whether the hormone is water or lipid soluble.

lipid soluble hormone receptors are

found internally

water soluble hormone receptors are found

externally

which type of hormone is going to activate/deactivate existing proteins?

water soluble hormone

which type of hormone is going to make new proteins

lipid soluble

multiple hormones may act on same target at the same time thru

• permissivness

• synergism

• antagonism

permissiveness

one hormone cannot exert its effects without another hormone being present

• ex. reproductive hormones need thyroid hormone to have affect, if TH is low (hypothyroidism), puberty is delayed

• ex. TH and Epi work better together, release a lot of fatty acids.

synergism

more than one hormone produces same effects on target cell, causing AMPLIFICATION

• ex. glucagon and epinephrine both cause liver to release glucose, but when cortisol is added glucose skyrockets.

• can work indepenently, but better together.

antagonism

one or more hormones oppose action of another hormone

• ex. insulin (brings sugar into cells) and glucagon (says to release sugar), PTH vs calcitonin