Module 9 - Endocrine

2 arteries: Sup. Thyroid a (off ECA); inf. thyroid a (off thyrocervical trunk)

3 veins: sup and middle vv (IJV); inf thyroid (into left brachiocephalic trunk)

• sup. suprarenal a: off of phrenic a
• middle suprarenal a: off of abdominal aorta
• inferior suprarenal a: off renal a

for both sides

• -Right: duodenum
• -Left: spleen
• -anterior: transverse mesocolon
• -posterior: aorta, renal vessels, left kidney, diaphragm
• -superior: splenic vessels
• -inferior: 3rd part of duodenum

• stomach: gastrin
• small intestine: secretin and CCK
• heart: ANP
• placenta: hCG

• -from endoderm
• -3rd pharyngeal pouch to inferior
• -4th pharyngeal pouch to superior

-think of it swinging down like a door

pulls the gonad into the pelvis.

• -peptide: bind to cell surface receptors, small proteins
• -amine: made from tyrosine and tryptophan, cell surface receptors except T3 and T4
• -steroid: derived from cholesterol, bind intracellular receptors that regulate gene transcription

• G alpha s activates
• G alpha i inhibits

• -pituicytes (glial cells)
• -fenestrated capp's
• -unmylinates axons (herring bodies at ends)

• acidophils:
•   -somatotrophs: GH
•   -lactotrophs: prolactin
• basophils:
•   -gonatotrophs: LH and FSH
•   -thyrotrophs: TSH
•   -corticotrophs: ACTH

• -hormones need iodine
• -can store hormones up to three months (in colloid)
• -although T3 and T4 are peptides, their receptors are intracellular

• 1) thyroglobulin is made in the follicular cell
• 2) Iodide is captured from the blood
• 3) Iodide is oxidized to I2 in the follicular lumen by thyroid peroxidase
• 4) Iodination of thyroglobulin to make MIT and DIT
• 5) coupling reaction MIT and DIT molecules are combined to make T3, two DIT make T4. All 4 molecules stay attached to thyroglobulin and hang out in the colloid until thyroid is stimulated.
• 6) thyroglobulin endocytosed when thyroid stimulated
• 7) lysosomal proteases break T3 and T4 (10x more T4) from thyroglobulin. T3 and T4 released to blood.
• 8) MIT and DIT are recycled as thyroglobulin and iodide is salvaged.

• -BMR increases
• -carb: inc. gluconeogenesis, inc. glycogenolysis, no effect on serum glucose
• -protein: increases synthesis and breakdown, increased muscle wasting
• -lipid: increased lipogenesis, increased lipolysis decreased serum cholesterol
• -increased thermogenesis
• -ANS: increased beta adrenoreceptors (increased sens to chatecholamines, which remain at normal levels)

• -bone: increase both osteoblast and osteoclast activity
• -liver: triglyceride and cholesterol metabolism
• -brain: axon growth
• -heart: increased iontropy and chronotropy, reduced peripheral resistance
• -adipose: breakdown of lipids
• -muscle: increased protein breakdown
• -gut: absorb more carbohydrates

T4 is converted to the more active T3 in the liver and kidneys via 5-ionidase

• -Hypo
•   -Cretinism: retardation due to low iodine
•   -Myxedema: dermal edema due to increased protein deposition
•   -Iodine-deficient goiter
• -Hyper
•   -Graves: B lymphocytes errantly produce TSI, which mimics the effects of TSH on the thyroid. produces a goiter and other problems

• 1)external Ca++ receptor stimulates G-alpha-q
• 2) splits PIP2 to IP3 and DAG
• 3a) IP3 releases Ca++ from ER
• 3b) DAG activates PKC
• 4) both the Ca++ (internal) and PKC stop the vesicles from being released and the PTH being released.

In MOST cells the Ca++ and PKC cause the hormone to be released, this is a special case!

• 1) promotes Ca++ reabsorption in the ascending LOH and DCT of nephron
• 2) reduces reabsorption of phosphates in PCT and DCT
• 3) creates active vit D, further promoting renal Ca++ reabsorption 
• 4) bone reabsorption further increasing serum Ca++

• 1) humoral: via blood flowing from the centre to the periphery of the islet
• 2) cell-cell: gap junctions
• 3) neural communications: innervated by symp and para.

• 1) increase glucose transport into cells
• 2) increase glycogenesis
• 3) increase lipogenesis and protein synthesis

-Type II diabetes is due to a problem with the insulin receptor or the subsequent cascade.

-Type I diabetes is a problem with the beta islet cells, can be immunological. 

-Lots of times with type II diabetes, the beta islet cells burn out after trying hard to lower the glucose levels (which aren't being lowered because of the broken receptors)

• 1) delta cells
• 2) D-cells of GIT
• 3) hypothalamus (paraventricular nucleus)

• 1) Glucose enters cell via the glut2 channel 
• 2) When there is high glucose, there will be higher ATP, which causes the Katp channels to close
• 3) this causes K+ to build up in the cell (along with the slow trickle of Na+ that was already coming in) causing depolarization
• 4) depol. triggers some voltage-gated Ca+ and Na+ channels to open
• 5) this causes further depolarization, opening the voltage-dependent calcium channels (VDCC) to open and let in a TON of Ca++
• 6) This Ca++ causes insulin exocytosis
• 7) K+ channel will cause reploarization

receptor tyrosine kinase (RTK) because it phosphorylates tyrosine residues on itself and other proteins.

• 1) receptor synthesis
• 2) endocytosis of receptors
• 3) endocytosis by degradation

• 1) number of receptors
• 2) receptor affinity for insulin
• 3) receptor's ability to transduce signal.

• 1) SH-2 proteins: bind and phosphorylate tyrosine groups on the insulin receptors (imp. for lipid metabolism)
• 2) TK can phosphor. and activate many cytoplasmic proteins
• 3) phosphor. insulin-receptor substrates (IRS), this one is most important

Liver, adipose tissue, muscles

• -stores glucose as glycogen
• - inhibits gluconeogenesis (via PEPCK) 
• -lipogenesis 
• -stimulate protein metabolism

• -uptake of glucose via glut4
• -convert glucose to glycogen
• -increase glucose breakdown
• -protein synthesis in skeletal muscle

• -increased uptake of glucose via GLUT4
• -increase breakdown of glucose
• -increase triglyceride formation
• -enhances production of lipoprotein lipase

• 1) diabetic retinopathy
• 2) diabetic nephropathy (affects SM in afferent arteriole)
• 3) diabetic neuropathy (PNS)

• central mechanism is atherosclerosis, leading to narrower walls
• 1) coronary artery disease/heart disease
• 2) stroke
• 3) peripheral artery disease

• 1) increase blood glucose concentration
• 2) anti-inflammatory activity (inhibits phospholipase A2, recall from earlier)
• 3) optimize vascular responsiveness to catecholamines
• 4) enhance glom. filtration rate
• 5) decrease osteoblast activity
• 6) decrease Ca+ absorption from GIT
• 7) alters CNS (mood and cognition)
• 8) may cause insulin resistance

• 1) renin-ANG II
• 2) ACTH
• 3) potassium levels

• Location: most symp. target cells
• affinity: NE>E
• typ. response: excitory
• example: increased SM contration

• Location: digestive system
• affinity: NE>E
• typ. response: inhibitory
• example of response: decreased motility

• location: heart
• affinity: NE=E
• typical response: excitory
• example of response: increased ionotropy and chronotropy

• Location: skeletal muscle, some smooth muscle in organs and selected BVs
• affinity: E only
• Typical response: inhibitory
• examples of response: bronch. dilation, arteriolar dilation in skeletal m arterioles and cardiac m