Endocrinology 9 Flashcards
List the non-classical endocrine organs (and compare/contrast with classical endocrine organs)
Brain – especially hypothalamus
Kidney – Renin, Vitamin D, erythropoietin
Heart – ANP, BNP
Liver – IGF-I
GI – small intestine, stomach (serotonin, ghrelin)
Organs/Tissues containing endocrine cells
- Brain – especially hypothalamus
- Kidney – Renin, Vitamin D, erythropoietin
- Heart – ANP, BNP
- Liver – IGF-I
- GI – small intestine, stomach
- Cells that also produce hormones
- Immune cells – macrophages, lymphocytes
- Platelets
Describe renin. Where produced? In what type of cells?
What is its function/role?
Kidney
Glycoprotein produced in juxtoglomerluar cells of afferent arterioles
Important regulator of arteriolar diameter
Cleaves angiotensinogen to angiotensin I (precursor for angiotensin II).
(Cleaves the Leu-Val bond
Describe EPO. What kind of hormone?
What kind of receptor?
Describe its action.
What factors regulate it? How will androgens and estrogens affect its release?
34 kDa protein made in kidney; tyrosine-linked kinase receptor
Stimulates proerythroblasts and differentiation of red blood cells (increases cell number)
Regulated by: Anemia Thyroid hormone Hypoxia (high altitude) Norepinephrine Androgens stimulate, estrogens inhibit
What is a major side effect of raising hematocrit too quickly?
What can result?
Describe pure red aplasia. What is it due to?
Why is this bad? (EPO and doping)
Major side effect of raising hematocrit too quickly = hypertension
Severe hypertension can lead to encephaly, seizures
Pure red cell aplasia – very rare now; likely due to injection preparations and not EPO
One study in mice – -transgenic overexpression of EPO
-Mice had demyelinating neuropathy, muscle degeneration, degenerative liver/kidney disease, shorter life span. No cardiovascular issues. Hematocrit = 0.89 (2x normal)
Describe atrial and brain natriuretic peptides (ANP, BNP).
Describe its function. How is hematocrit affected?
Affects blood vessel function:
- decrease vascular smooth muscle tone
- decrease peripheral vascular resistance
- increase capillary permeability.
**This generates a significant increase in hematocrit
What factors can influence blood vessel function?
What is the net effect of ANP/BNP in kidneys? In blood vessels?
Blood vessel function is influenced by factors at many levels: kidney, vessels, nervous system, adrenals, etc.
Net effect in kidneys is diuresis (excretion of urine) and natriuresis (excretion of sodium).
Net effect in blood vessels = decreased blood pressure
Describe Starling forces. What are the driving forces for bulk water movement?
Starling forces = driving forces for bulk water movement is transcapillary hydrostatic pressure difference and effective osmotic pressure difference.
Where is ANP released from? BNP?
Describe their role.
ANP – released from atrial myocytes
BNP – released from ventricular myocytes
**released in response to stretch – mechanical stimuli
Both are potent vasodilators
Increase natriuresis – excretion of sodium
Which has a longer half life ANP or BNP?
What do normal levels indicate?
Higher levels?
Lower levels?
How do they change with age?
How are levels different in men vs women?
- BNP – longer half-life than ANP making it a
useful diagnostic tool - Normal levels can rule out congestive heart
failure - Higher levels associated with heart and renal
failure - Lower levels with obesity
- Increases with age
- Higher levels in women
Draw a flow chart of downstream physiological effects of ANP and BNP. What kind of receptors?
Vessels: How is tone and capillary permeability affected?
Cell proliferation?
Nervous system:
Renal symp. activity?
Cardiac and pulmonary chemio and baro receptors?
Salt and water appetite?
Release of ADH?
Kidney: Glomerular effects: Afferent arteriole tone? Efferent arteriolar tone? Glomerular filtration? Blood flow? Renin release? Tubular effects: Collecting duct sodium reabsorption? Starling forces? Osmotic gradient?
Adrenal cortex?
Aldosterone synthesis and release?
ANP and BNP are
released from cardiomyocytes in response to mechanical stimuli - stretch.
Target organs
include kidney, adrenal cortex, blood vessels, and heart. Primary outcome is increased diuresis/Na+ excretion and vasodilation, thus lowering effective circulating volume blood
pressure.
SEE PAGE 4 OF HAND OUT
What does Polychlorinated biphenyl (PCB) do?
What is the result?
Competes with thyroid hormone for binding to its transport protein in the blood. (TTR; TBG)
Result: circulating thyroid hormone is degraded faster causing compensatory increase
in thyroid hormone production.
Result:
-Increased breakdown of thyroid hormone
-Compensatory excessive production by thyroid gland
-Goiter (enlarged thyroid gland)
Also causes cancer, immune function suppression (atrophied thymus), reduced sperm count, neurological deficits
banned by EPA in 1979, but still present in many products and emitted from hazardous waste sites. (Slide 11)
Describe Diethylstilbestrol (DES).
What is found in?
What is it used to treat?
Non-steroidal synthetic estrogen
Used in cattle feed
Given to pregnant women from 1940-1970 (“DES Daughters”) to reduce complication
associated with pregnancy.
“DES daughters” = 40% increase in cervical/vaginal cancers
Used for prostate cancer treatment
Birth Control Pills in water? Myth?
What are estrogenic compounds found in water?
Synthetic estrogen (EE2) is minimal or nonexistent in drinking water.”
Other estrogenic compounds in water:
Pesticides (Atrazine)
Estrogens given to livestock
Industrial chemicals (bisphenol-A)
Synthetic estrogens from over the counter birth control pills are
inconsequential. However,
environmental estrogens from other sources (i.e. pesticides, industrial chemicals, livestock) can
have physiological consequences for both humans and animals.
Describe BISPHENOL A (BPA).
What is it used in? What are physiological consequences?
Used in: food packaging, toys, lining of canned foods and beverages
EVERYONE IS EXPOSED ALL OF THE TIME – 93% of Americans have detectable BPA in their urine.
Physiological Consequences:
- Estrogenic
- Obesogenic and diabetogenic (alters lipid homeostasis and pancreatic beta cell function)
- Neurological effects
- Antagonist for thyroid hormone receptor
- Reproductive and developmental effects (male and female)
- Cardiovascular disease – evidence for arrhythmias and atherosclerosis
Describe substitutes for BPA. What are they? What is important to note about BPA-free products.
BPA substitutes – BPS and BPF
What is known about these substitutes?
As of July 2015 there were 32 studies. Most found that they had similar endocrine actions as BPA. (Rochester and Bolden, Environ. Health Perspectives, 2015)
Recent study showed BPS is risk factor for developing T2DM.
Consumers can buy products that are labelled “BPA-free” and these products likely contain BPS or BPF.
