lecture 2: cell comm and endocrinology (not completed)

endocrine system

regulators of body function through release of hormones

7 glands of the endocrine system

pituitary

thyroid

parathyroid

ovary

testes

adrenal (cortex and medulla)— stress

pancreas— blood glucose regulation

hypothalamus

neural, hormone release

other tissues

GIT, adipose, liver, etc

juxacrine

cells touching or located next to another (juxtaposition)

endocrine

travel through blood

autocrine

chemicals that interact with the cell that secreted it

(histamine during inflammation)

paracrines

chemical that communicate with neighboring cells

(interleukins released during immune responses)

neurotransmitters

chemicals released by neurons into synapse (gap between neutrons

(specific form of paracrine; ex: acetylcholine)

hormones

released by endocrine glands, secreted into interstitial fluid, diffuse into blood and travel to distant target

(insulin)

neurohormones (neuroendocrine)

neurotransmitter released and travels outside brain

(antidiuretic hormone)

peptide hormone

chains of amino acids and proteins

(insulin, oxytosin)

amino acids and derivates

amines (made from amino acids)

(epinephrine, serotonin)

lipid hormones: steroids

derived from cholesterol

(estrogen, testosterone, cortisol)

lipid hormones: eicosanoids

derived from arachidonic acid

(prostaglandins, leukotrienes)

receptor categories

ligand-gated channels, G-protein coupled receptors, catalytic receptors, nuclear receptors, receptors that undergo cleavage

steps in signal transduction

recognition

transduction

transmitted

modulation

cellular response

termination

ligand-gated receptor

integral membrane protein

binding of receptor opens a channel

communication between electrically excitable cells

catalytic receptors

integral membrane protein

enzymes or part of enzyme complex

ex: receptor tyrosine kinase (RTK)

protein kinase

transfers a phosphate group to a protein

phosphatases

removes phosphate group from a protein

G protein-coupled receptors (GPCR)

1. ligand bonds

2. GTP leaves, GDP comes in

3. alpha leaves beta-gamma to trans. signal

Amplifier enzyme: phospholipase C steps

ligand bonding

GTP leaves, GDP comes in

PLC splits PIP2 into IP3 and DAG

• DAG activates PKC

• IP3 goes to ER

nuclear receptors

proteins in cytosol or nucleus

ligand-activated transcription factors

ex: steroid hormones (hydrophobic)

1. hormone enters cell

2. it binds to receptor

3. receptor goes to nucleus

4. acts as transcription factor

5. more mRNA

6. new protein

complementary actions

growth controlled by GH, insulin, IGF-1, sex hormones, etc

anterior pituitary

GH, TSH, ACTH, FSH, LH, PRL

• somatotrophs— growth hormone (somatotropin)

• lactotrophs— produce prolactin

• gonadotrophs— follicle stimulating hormone, luteinizing hormone

• thyrotrophs— thyroid stimulating hormone (TSH)

• corticotrophs— adrenocorticotropic hormone (ACTH), beta-lipotropin (cortisol)

posterior pituitary

AVP, oxytocin

hyperplasia

cells dividing

hypertrophy

cells get bigger

mechanism of GH release

1. hypothalamus releases GHRH (growth hormone releasing hormone)

2. GHRH travels to anti. pit. through a capillary system

3. GHRH binds its receptor on somatroph

4. GDP exchanged for GTP

5. Gas dissociate and binds AC

6. AC converts ATP to cAMP

7. cAMP activates protein kinase A

8. PKA phosphates ca++ channel

9. ca++ floods cell + causes exocytosis

10. GH —> blood

1. somatostatin (SS) released from hypothalamus and goes to ant. pit.

2. SS binds its receptor (GPCR)

3. GTP comes in, GDP leaves

4. Gai dissociates and binds AC and inhibits it

IGF-1 release

1. GH exits blood at liver

2. GH binds to receptor

3. receptor (RTK) dimerizes

4. receptor RTK dimer phosphorylates itself and then “other things”

5. phosphorylation of a transcription factor = increased transcription of IGF-1

6. IGF-1 translated and exocyted

7. IGF-1 goes to the blood and binds IGF binding protein

8. IGF-1 dissociates from IGFBP and exits blood at tissue

9. IGF-1 binds receptor

10. receptor will dimerize

11. RTK phosphorylates

12. increased transcription and translation

other growth-promoting hormones

thyroid hormones (increase)

sex steroids (gonadocorticoids) (increase)

glucocorticoids (decrease) (stress)

insulin

others: nerve growth factor, fibroblast growth factor, epidermal growth factor, etc

stress response

triggered by many different stressors

hypothalamic corticotropin-releasing (CRH) hormone starts process

stimulates adrenal cortex to release glucocorticoids

adrenal gland

pyramid-shaped organs above the kidney

2 glands in one:

• adrenal medulla

• adrenal cortex

corticosteroids - all from cholesterol

• zona glomerulosa- mineralcorticoids

• zonal fasciculata - glucocoricoids

• zona reticularis - gonadocorticoids (sex hormone)

adrenal medulla

nervous tissue; epinephrine and norepinephrine

adrenal cortex

layers of glandular tissue that secrete corticosteroids

What does cortisol do?

activation of many glucocorticoid-responsive genes

• gluconeogenesis- breakdown of fat and protein into glucose

activation of anti-stress pathways

activation of anti-inflammatory pathways