PHCL Exam 2 Flashcards
The Hypothalamic-Pituitary-Adrenal (HPA) Axis
is one mechanism our body uses to respond to stress (fight or flight response).
Stress -> Hippocampus-> Hypothalamus-> (Vasopressin, CRF)-> Pituitary-> to the blood-> (ACTH) Adrenal Cortex-> Cortisol
Cortisol can feed back to the
pituitary and hypothalamus to reduce further stimulation of the system (feedback inhibition)
Where is aldosterone made
in the zona glomerulosa
where are cortisol and androgens made?
zona fasciculata/zona reticularis`
where is epinephrine and norepinephrine made ?
in the adrenal medulla
Maastricht acute stress test
(hand in cold water and mental arithmetic)
men tended to release cortisol
faster and with a higher peak than women during this test.
Where are CYP11B1 and CYP17 expressed in the adrenal gland?
since they are enzymes for Cortisol in the ZF/ZR
diurnal cycle of serum glucocorticoids
: lowest in the middle of the night, but peaks in the morning – probably helps with waking.
No average difference between girls and boys, age, puberty, etc., but a lot of variance in the individual levels of glucocorticoids
Stress increases glucocorticoid release into blood
which typically is quickly resolved. But inappropriate
stress responses can result in too much/too long, or weak HPA axis response.
Corticosteroids
regulate energy metabolism, increase short-term memory (good for learning/tests!), maintain bp, inhibit inflammation, help with fetal lung development
Corticosteroid deficiency
Addison’s disease. Causes low blood sugar, low bp, weakness, muscle/joint pain, skin darkening or vitiligo,
salt craving (reduced salt, increased potassium) nausea/diarrhea, depression. These can be very dangerous if not controlled.
Corticosteroid overload
Cushing’s Syndrome. Skin thinning, depression/mood swings, memory loss/learning disability,
muscle wasting, poor wound healing/suppressed immune system, hypertension, diabetes, osteoporosis, anovulation
clinical causes for Addison’s disease
autoimmunity
Darkening of skin
Low blood sugar
Salt craving
clinical causes for Cushing’s syndrome.
Skin thinning
Diabetes
Delayed wound healing
Suppressed immune
response
Hypertension
Cortisone
isolated in the 1940s and used for rheumatoid arthritis for the first time in 1948 – quickly became a widely used drug.
Discussed multiple therapeutic uses of corticosteroids
- Energy metabolism
- stimulate gluconeogenesis (making glucose from non-
carbohydrate sources) - inhibit glucose uptake by muscle or adipose tissue
- increase protein and lipid catabolism
- increase serum glucose levels
- Increase short term memory
- Maintaining vascular tone
- Inhibit pro-inflammatory cytokines
- Fetal and neonatal lung development
- Inhibition of ACTH release by the anterior pituitary
(feedback regulation)
Discussed therapeutic vs adverse effects of glucocorticoid use. Dose and length of treatment are important.
therapeutic:
anti-inflammatory and immunosuppressive
decrease pain
decrease swelling
decreased stiffness
decrease physical disability
adverse:
increased cardio risk
infections
myopathy
glaucoma
hirsutism
skin thinning
gastric ulcer
Glucocorticoids regulate 10-20% of genes in your body.
Bind to glucocorticoid receptor (GR) inside cells – can be alpha (active) or beta (blocks alpha)
Glucocorticoids bind with great affinity
to corticosteroid binding globulin (CBG) in plasma – not very well to albumin.
glucocorticoids bind to their receptor,
cause dimerization, translocate to the nucleus and bind to DNA to regulate transcription
of target genes.
Regulation of genes by the GR can either involve
transactivation of target genes, or transrepression (messing up other transcription
factors). Net result is increase in anti-inflammatory gene expression, decrease in pro-inflammatory gene expression
what can stressors lead to?
Repeated stress can lead to habituation, but some forms of chronic stressors (e.g., severe pain, blood loss, hypoglycemia)
can lead to no habituation. In both cases a novel stress can cause a hyper-response of the HPA axis
understand where estrogen is made and primary function
made from: theca cells from the follicle take LH and cholesterol and turn it into androstenedione and androstenedione goes to granulosa cells where FSH and androstenedione and aromatase make estradiol
primary function:
understand interplay and origins of GnRH in normal ovarian function
interplay:
origins: produced by hypothalamus
understand interplay and origins of LH in normal ovarian function
interplay:
origins:
understand interplay and origins of FSH in normal ovarian function
interplay:
origins:
understand interplay and origins of estrogen in normal ovarian function
interplay:
origins:produced by growing follicle
understand interplay and origins of progesterone in normal ovarian function
interplay:
origins:
how does the pituitary and gonadal hormones regulate each other
how does tamoxifen work
Define Sertoli cells and their function
understand interplay and origins of GnRH in normal testicular function
interplay:
origins:
understand interplay and origins of FSH in normal testicular function
interplay:
origins:
understand interplay and origins of estrogen in normal testicular function
interplay:
origins:
understand interplay and origins of LH in normal testicular function
interplay:
origins:
understand interplay and origins of testosterone in normal testicular function
interplay:
origins:
Define Leydig cells and their function
how does mifepristone work
where is insulin produced
where is glycogen produced
where is glucagon produced
where is glucose produced
Islet of Langerhans in the pancreas is responsible for
insulin and glucagon release
alpha cells release
glucagon. Stimulates breakdown of glycogen to produce glucose (liver, muscle
beta cells release
insulin, C-peptide, amylin. Insulin stimulates glucose uptake into cells
delta cells release
somatostatin
G cells release
gastrin
F cells release
pancreatic peptide release
Therapeutic insulin,
Exenatide
(GLP-1 receptor agonist, blocks glucagon release)
Pramlintide
(binds amylin receptors to decrease appetite)
Octreotide
(mimics somatostatin, blocks growth hormones,
glucagon and insulin)
Cleavage of pro-insulin by proprotein convertases (enzymes) create
functional insulin and its by-product, C-peptide
Discussed symptoms and definitions of diabetes
Discussed causes of Type 2 Diabetes
Discussed some basic metabolic differences between non-diabetic and diabetic people
Discussed cellular causes of insulin resistance:
insufficient insulin receptors or improper signaling downstream of
the receptors
Discussed complications and basic management of diabetes
Discussed A1C
: a measure of glycation of blood hemoglobin
Metformin
Metformin. Targets AMPK (or AMPKinase), which inhibits glucose
production in the liver. Class of drugs called Biguanides
Sulfonylureas
(close K+ channels), GLP-1 Receptor Agonists, DPP-4 inhibitors
GLP-1 receptor agonists
GLP-1 stands for glucagon-like peptide-1. Receptor is found on beta cells. GLP-1 receptor agonists = decrease glucagon and increase insulin.
DPP-4 inhibitors
DPP-4 is an enzyme that breaks down GLP-1 in the body. Inhibiting this enzyme allows for more
GLP-1, so more insulin release
Discussed basic organ system signaling during fasting versus prandial state
Food, glucagon and glucocorticoids can all
increase blood glucose levels
Glucose Glut2 transporter on beta cells ATP block potassium channel causes opening of Calcium channel
vesicles release insulin
insulin Insulin receptor on muscle/fat signaling translocation of Glut4 vesicles to membrane
understand interplay and origins of estrogen in normal testicular function
interplay:
origins:
Understand the therapeutic uses of testosterone/anabolic steroids and
antiandrogens and side effects
