Hormone basics; Bone and Mineral regulation Flashcards
Classical endocrine glands (3P’sand TOATs)
Pituitary
Parathyroid
Pancreas (Islet cells)
Thyroid
Ovaries
Adrenal
Testes
Non-classical glands (+ examples of their secretions)
Heart (ANP and BNP)
Kidney (erythropoietin + renin) - “kidney’s renin (raining) blood”
Adipose tissue (leptin and adiponectin) - leptin + adiponectin make u fat
Gut (CCK + incretins) - CCkant INCREase this gut
Stomach (gastrin)
Osteocytes (FGF23)
Glycoprotein hormones and where they’re released from
Anterior pituitary
FSH
LH
TSH
Steroid hormones and where they’re released from
Gonads: estradiol, progesterone, testosterone
Adrenal gl: cortisol, aldosterone
Small molecules and where they’re released from
Thyroid: T3/T4
Adrenal gl: Epinephrine
Peptide hormones and where they’re released from
Pancreas: insulin, glucagon and STS
Parathyroid: PH
Posterior pituitary: Vasopressin + oxytocin
Thyroid: Calcitonin
Hypothalamus: TRH + GnRH
Anterior pituitary: Growth hormone + Prolactin
Why is hormone binding to plasma proteins important (3 reasons)?
Between bound and free hormone, which one is biologicaly active?
Reservoir for hormone (if you have low levels or something)
Slows metabolism/turnover of hormones (e.g. by degradative enzymes)
Delivery of hormone to peripheral tissues
Free hormone is biologically active
Hormone receptor types
GPCRs
Tyrosine/Serine kinase receptors
Cytokine receptors
Nuclear receptors
GPCR binding hormone examples
Epinephrine, ACTH, TSH
Tyrosine/Serine kinase receptor hormone examples
Tyr kinase rec: insulin, FGF23
Serine kinase rec: inhibin, activin
Cytokine receptor hormone examples
Growth hormone, Prolactin, Leptin
Nuclear receptor hormone examples
Steroid hormones
T3 and T4
125-OH-D
Draw a basic negative feedback loop. Describe glucose homeostasis (opposite effects of insulin and glucagon).
Which pancreatic cells are secreting insulin/glucagon?
What are three other examplesof negative feedback discussed? (hint: 2 involve the pituitary)
Beta cells - insulin
Alpha cells - glucAgon
TSH/T4 loop from pituitary gl
ACTH/Cortisol loop from pituitary gl
PTH/serum Ca2+ loop from parathyroid gland
Draw and describe a basic positive feedback loop.
Describe the LH surge in terms of positive feedback (i.e. what’s the role of estradiol?)
Normally, LH/FSH stimulate an increase in estradiol, which in turn feeds back and inhibits LH/FSH release
LH surge: increased estradiol levels stimulate LH levels
Baseline lab tests done to assess endocrine function
Urine hormone levels
Hormone levels (just regular)
Clinical chemistry testing (e.g. hemoglobin A1C level/glucose testing for diabetes)
What’s the difference between stimulation and suppression tests for dynamic testing?
How would you conduct each test?
Stimulation testing - looks at whether pt can make the hormone in question
To conduct the test - administer a stimulus e.g. ACTH to see if glands respond and secrete normal cortisol amounts
Suppression testing - looks at whether pt can regulate the hormone in question
To conduct the test - administer exogenous hormone to see if the negative feedback loop will work like its supposed to e.g. give synthetic corticosteroid which should suppress ACTH ad lower cortisol production
What’s happening with the imaging below for thyroid gland function?
The cold nodule: too little thyroid hormone in that region (the rest has normal levels); as cell mutates, it can’t take up iodine (more concerning for malignancy)
The hot nodule: Too much thyroid hormone in that region, the rest of the gland is suppressed
What are the causes of endocrine disease?
Genetic mutations
Autoimmunity
Neoplasms
3 kinds of mutations that cause endocrine disease + examples for each
Mutations in genes encoding hormones: Leptin, FGF23
Mutations in hormone receptors: PTH receptor, LH receptor
Mutations in enzymes necessary for hormone synthesis
2 effects of autoimmunity that lead to endocrine disease
Destruction of endocrine glands: Thyroid, Beta cells in pancreas
Antibodies directed against cell surface receptor: TSH, insulin
(Hyperthyroidism (Grave’s disease) – antibodies bind to cell surface receptors and act like TSH, which stimulates the downstream pathways, which leads to excess thyroid hormone secretion;
Hypoglycemia – ab’s bind to insulin receptor and act like insulin >> excess uptake of blood glucose)
What are the syndromes of excess and deficieny for the following peptide hormones:
PTH
Insulin
PTH: excess = hypercalcemia due to hyperparathyroidism
deficiency = hypocalcemia due to hypoparathydoidism
Insulin: excess = hypoglycemia; deficiency = Type 1 diabetes
What are the syndromes of excess and deficiency for the following steroid hormones:
Testosterone
Estradiol
Cortisol
Testosterone
excess: precocious puberty; deficiency: hypogonadism
Estradiol
excess: ovarian tumor; deficiency: menopause
Cortisol:
excess: Cushing’s syndrome; deficiency: adrenal insufficiency/Addison’s disease
What happens in untreated congenital adrenal hyperplasia? (hint: this is an e.g. where you have both excess and deficiency)
What’s in excess and what is deficient?
No cortisol production >> increased CRH and ACTH but still no cortisol made >> accumulation of other things like androgens (so result: excess androgens but deficient cortisol)
What are the ways to treat hormone deficiency?
Hormone replacement (hormone itself or downstream hormone)
Drugs to stimulate hormone-secreting gland
Treat deficiency symptoms e.g. to treat hypocalcemia, give Ca2+/Vit D supplements
What are the ways to treat hormone excess?
Surgical removal of hormone secreting cells
Radiation
Drug treatment to block hormone synthesis, secretion, action
What is the impact of acidemia/alkalemia on ionized Ca2+?
How would you determine the correct amount of ionized calcium?
Acidemia: more protons available to bind to negatively charged albumin >> displaces Ca2+ >> increases free ionized Ca2+ conc
Alkalemia: more calcium bound to albumin >> decreased conc of free ionized Ca2+
Ionized calcium measurement: total Ca2+ + (4-Albumin amount)*0.8)
In what form is PTH synthesized? Is PTH release continuous? Which segments of intact PTH are active?
Graphically, what is the relationship between PTH and Ca? (interpret the graph below)
What is the Ca set point?
Prepropeptide
Yup. Continuous release
N terminus (first 34 aa’s) active (less than 20 min half life)
Sigmoidal relationship between PTH and Ca/small Ca changes = large PTH response changes
Ca set point = half maximal PTH secretion
Describe the role of the Ca sensor (CaSR) in Ca balance (i.e. what happens when extracellular Ca2 is high/low?)
(normally) CaSR senses high extracellular ca levels >> Gi is active>> PTH release is inhibited
(low extracellular Ca) Not enough Ca to bind CaSR >> Gi isn’t active >> PTH released >> increased Ca reabsorption
Recall the sigmoidal relationship between PTH and Ca. What happens when you have a CaSR inactivating mutation?
What is the ultimate effect of this situation?
CaSR inactivating mutation:
Inactivated CaSR essentially the same as having low extracellular calcium except the receptor is dead
Result is hypercalcemia because PTH keeps being released
Curve shifts to the right; set point becomes higher
Recall the sigmoidal relationship between PTH and Ca. What happens when you have a CaSR activating mutation?
What is the ultimate effect of this situation?
Overactive CaSR means more PTH release inhibited
Result is hypocalcemia because PTH isn’t released so Ca levels stay low
Curve shifts to the left; set point becomes lower
What is the role of PTH in bone formation? (hint: on what cell is the PTH receptor located)?
What are the functions of RANK ligand and OPG? Which cell secretes those?
Describe the effect of prolonged vs brief PTH exposure in bone resorption
PTH binds to osteoblasts (receptor on osteoblasts) >> promotes release of RANKL or OPG
RANKL binds to osteoclasts >> promotes resorption
OPG binds to RANKL and prevents it from binding to its receptor >> prevents resorption
Brief exposure to PTH = activates osteoblasts >> promotes bone formation
Prolonged exposure to PTH = activates osteoblasts to release RANK ligand >> activates osteoclasts which promote bone resorption
Describe the process of PTH mediated Ca reabsorption in the Distal Conv tubule
PTH binding to GPCR (Ga subunit = active)>>
Activation of Adenylyl Cyclase >>
+ cAMP levels >> + PKA >>
Insertion of ca channels on luminal side >>
+ intracellular Ca levels >> Ca sequestration by Calbindin >>
Release of Ca2+ and reabsorption via basolateral Ca2 ATPase and NCEX
Outline the pathway of Vitamin D activation.
Which form is the major circulating form of VitD that’s also tested for VitD deficiency?
What 2 factors stimulate the production of 1,25 OH D?
What are the enzymes that lead to production of 1,25 OH D and 24,25 di OH D?
T/F: 1,25 OH D and 24,25 OH D are already in their water-soluble states so once made, they can just be excreted
25 alpha hydroxylase - major circulating form
Increased PTH and low phosphorus - stimulate 1alpha hydroxylase
125 OH D - 1a hydroxylase; 24,25 diOH D - 24a hydroxylase
Falsehood. 24,25 diOH D is water soluble but 125 OH D has to be converted to the water soluble version by 24a hydroxylase
Describe the functions of the hormones below in Ca regulation
Describe the role of WNT signaling in bone formation. What is the role of beta catenin in this pathway?
WNT promotes osteoblast differentiation: beta catenin binding to nuclear receptors >> activates WNT genes >> osteoblast differentiation
Where is sclerostin secreted from and what does it do?
Sclerostin secreted by osteocytes;
Recruits osteoclasts and promotes osteoclast activity
Decreases mesenchymal stem cell differentiation into osteoblasts and prevents WNT signaling
What’s osteoporosis? Is bone normal in structure in this disorder?
What causes osteoporosis?
- Bone is normal in structure, but there is less of it
- Reduced bone strength, increased bone fragility
Lack of peak bone mass, loss of bone or both
What’s osteomalacia?
Bone is made but doesn’t get mineralized so its soft
