79 - Non-classical gland + endocrine disruptors Flashcards
Recall: what are the important non-classical endocrine glands to know?
- Brain, especially hypothalamus
- Kidney (Renin, Vitamin D, erythropoietin)
- Heart (ANP, BNP)
- Liver (IGF-I)
- GI, small intestine, stomach (serotonin, ghrelin)
What are some immune cells that also produce hormones?
Macrophages, lymphocytes
Where what type of protein is renin and where is it produced, specifically?
Glycoprotein
- Juxtaglomerular cells of afferent arterioles
What stimulates/inhibits the release of renin?
Reduction in afferent arteriole pressure causes release of renin from the JG cells; increased pressure inhibits renin release
What does renin do?
Cleaves angiotensinogen to Ang I
What is the size of EPO, in kDa?
34 kDa
Where is EPO made?
Kidney
What type of receptor does EPO bind?
Tyrosine-linked kinase receptor
What is the effect of EPO (by stimulating what cell)?
Stimulates proerythroblasts and differentiation of RBCs to increase cell #
Name the 6 regulators of EPO (5 stimulate, 1 inhibits)
- Anemia
- TH
- Hypoxia (high altitude)
- NE
- Androgens stimulate, estrogens inhibit
Why is EPO blood-doping bad?
Major side effect of raising Hct too quickly = HTN
What can severe HTN lead to?
Encephalopathy, seizures
Pure red cell aplasia (anemia of RBC precursors) has been seen in EPO blood-doping (rare). How does EPO cause it?
Trick: likely due to injection preparations and not EPO
In the heart, what cells release ANP and what cells release BNP?
- ANP released from atrial myocytes
- BNP released from ventricular myocytes (released in response to stretch)
Which is a better clinical marker, ANP or BNP? Why?
BNP, it stays in the bloodstream much longer than ANP
What are the effects of ANP and BNP?
- Both are potent vasodilators
- Increase natriuresis (excretion of Na+), diuresis (excretion of urine)
What are the 3 ways in which ANP/BNP affect bv function?
How does this affect Hct?
- Decrease vascular smooth muscle tone
- Decrease peripheral vascular resistance
- Increase capillary permeability
- Significantly increases Hct
Normal levels of BNP can r/o what disease?
CHF
Higher levels of BNP are associated w/what 2 diseases?
Heart and renal failure
Lower levels of BNP are associated w/what common disease?
Obesity
How do ANP/BNP levels change w/age?
Are their levels higher in women or men?
- Increase w/age
- Higher in women
What is the name of the receptor that ANP/BNP bind, and what type of receptor is it?
NPR-A
- GPCR (increases cGMP)
What are the target organs of ANP/BNP? (4)
Kidney, adrenal cortex, bv’s, heart
What is ANP/BNP’s effect on the renal cortex?
Decreased aldosterone synthesis
What are the effects ANP/BNP have on the kidney? (many, so just read and understand)
- Decreased afferent arterial tone
- Increased efferent arterial tone
- Increased GFR
- Increased blood flow
- Decreased renin release
- Decreased collecting duct Na+ reabsorption
- Decreased Starling forces
- Decreased osmotic gradient
How does ANP/BNP affect sympathetic input to the kidney?
Decreases it, thus decreasing Na+ reabsorption and decreasing renin release
Define endocrine disruptor.
Chemicals that may interfere with the body’s endocrine system and produce adverse developmental, reproductive, neurological, and immune effects
Discuss the history of PCB.
Banned by EPA in 1979, but still present in many products and emitted from hazardous waste sites.
What is the disruptive action of polychlorinated biphenyl (PCB)?
Compete with TH binding to its transport protein in the blood (TTR; TBG)
- Result: Increased breakdown of thyroid hormone; compensatory excessive production by thyroid gland
What’s the major symptom of PCB exposure?
What else does it cause?
- Goiter
- Also causes cancer, immune function suppression (atrophied thymus), reduced sperm count, neurological deficits
What is diethylstilbestrol (DES)?
Also, what’s its hx?
- Non-steroidal synthetic estrogen
- Used in cattle feed
- Given to pregnant women from 1940-1970 to reduce complications
- Also used for prostate Ca tx
What are “DES daughters” and granddaughters?
40% increase in cervical Ca for pregnant women’s daughters who were given DES as a synthetic estrogen.
- Their gametes were affected too, so the granddaughters also had increased incidence of cervical Ca
(note: synthetic estrogen from OTC BCPs are inconsequential)
What is bisphenol-A (BPA)?
What is bad about it?
Chemical used in food packaging, toys, lining of canned foods and beverages
- Found to be estrogenic
(93% of Americans have detectable BPA in their urine)
Besides being estrogenic, what other consequences are there to BPA exposure?
- Obesogenic and diabetogenic (alters lipid homeostasis and pancreatic beta cell function)
- Neurological effects
- Antagonist for TH receptor
- Reproductive and developmental effects (male and female)
- CVD: evidence for arrhythmias and atherosclerosis
Are substitutes of BPA, such as BPS and BPF, safe?
No!
