Endocrinology - Lecture 3 Flashcards
What is the parathyroid hormone secreted from?
parathyroid chief cells in the thyroid
How many parathyroid glands are there and where are they located?
4, located on the back side of the thyroid
What happens to plasma calcium levels when parathyroids are removed?
there is a severe drop = convulsions and death
What is the structure of parathyroid hormone?
N-terminal 34 amino acid
What is the larger protein that undergoes proteolytic cleavage to produce parathyroid hormone?
preproparathyroid hormone
What is the half-life of parathyroid hormone?
3-18 minutes
What is the main function of the parathyroid hormone?
increase the concentration of plasma calcium
What does PTH do to bone resorption?
it increases bone demineralization
What does PTH do to the kidneys?
it increases the reabsorption of Ca++ in proximal convoluted tubule
What does PTH do to vitamin D synthesis?
stimulates the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3
Where does PTH stimulate the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3?
in the kidney
What does PTH do to the gut?
it facilitates the absorption of Ca++ from the gut
What does PTH use in the gut to facilitate the absorption of Ca++?
1,25D3
What controls PTH release?
the circulating concentration of calcium
What is the mechanism of PTH activity?
it binds to cognate receptor on target cells
What is hypoparathyroidism?
low levels of PTH in circulation
What are the 3 symptoms of hypoparathyroidsim?
- hypocalcemia
- decreased vitamine D production
- tetany
What level of calcium needs to be present in the body for there to be muscle spasms in hypoparathyroidism?
<7mg/100mL
What is the treatment for hypoparathyroidism?
administration of 1,25-dihydroxyvitamin D and calcium supplements
What is hyperparathyroidism?
parathyroid adenoma of parathyroid producing too much PTH
What two substances are produced too much in hyperparathyroidism?
- PTH
- 1,25D3
What does high PTH stimulate in hyperparathyroidism?
bone resorption and calcium reabsorption from the kidney
What does 1,25D3 increase in hyperparathyroidism?
calcium absorption from the intestines
How are the levels of calcium describes in hyperparathyroidism?
elevated
What is a common symptom of hyperparathyroidism?
kidney stones
What are the symptoms of severe cases of hyperparathyroidism?
cardiac arrhythmias, depressed neuromuscular excitability, calcium deposition on walls of blood vessels and cartilaginous regions of bones
What is the treatment for hyperparathyroidism?
removal of affected parathyroids and replacement therapy of 1,25D3 and Ca++
How can we get vitamin D from our diet?
cod liver oil, fatty fish
Why is vitamin D not a vitamin?
because it can be synthesized from a cholesterol metabolite
What are the 3 steps in the synthesis of vitamin D?
- UVB light + 7-dehydrocholesterol in the skin
- 25-hydroxylation in liver
- 1-hydroxylation in kidney and several peripheral tissues -> 1,25-dihydroxyvitamin D3
What is the primary function of vitamin D?
increases calcium absorption from the intestine
What are the 2 secondary functions of vitamin D?
- regulates immune system (protects against infection, anti-inflammatory)
- anticancer properties
When is vitamin D synthesis increases?
in conditions of low calcium when PTH is also increases
When is vitamin D synthesis decreased?
when calcium is high
What is Rickets?
absence fo UVB leading to vitamin D deficiency and deficient bone mineralization
What does low vitamin D lead to in adults?
osteomalacia
What is calcitonin made of?
32 amino-acid calcium-loweing peptide hormone
Where is calcitonin manufactured?
in parafollicular cells of the thyroid gland
What is the function of calcitonin?
lowers plasma calcium
How does calcitonin lower plasma calcium?
- promoting transfer of Ca++ from blood to bone
- increasing urinary excretion of Ca++
Rise in plasma Ca++ ___ the release of calcitonin.
increases
Decrease in plasma calcium concentration ___ the release of calcitonin.
decreases
Calcitonin is of ___ importance than PTH and 1,25D3.
lesser
Does the absence of calcitonin compromise calcium homeostasis?
no
Where are adrenal glands located?
adjacent to the upper surface of the kidneys
Are adrenal glands heavier in males or females?
males
What are the 2 tissues found in the adrenal glands?
cortex and medulla
What is the histologic appearance of the cortex?
large-lipid containing epithelial cells
What is the histologic appearance of the medulla?
chromaffin cells-fine brown granules when fixed with potassium bichromate
What is the origin of the cortex?
derived from mesoderm
What is the origin of the medulla?
derived from the neural crest
What is the function of the cortex?
produces steroid hormones
What are the 3 hormones that the cortex produces?
- glucocorticoids
- mineralocoirticoids
- progestins
What are the 4 hormones that the medulla produces?
- catecholamines
- epinephrine
- norepinephrine
- some peptide hormones
What are the 3 layers of the adrenal cortex called?
- zona glomerulosa
- zona fasciculata
- zona reticularis
What does the zona glomerulosa produce?
mineralocorticoids (aldosterone)
What does the zona fasciculata produce?
glucocorticoids (cortisol)
What does the zona reticularis produce?
glucocorticoids, progestins, androgens and estrogens
What is the synthesis of adrenal steroids controlled by?
adrenocorticotropin ACTH
Which zone is 18-hydroxylase present in?
zona glomerulosa
Which zone is 17a-hydroxylase not present in? Why?
zona glomerulosa, because this zone does not produce glucocorticoids
What is the function of steroid hormones?
to regulate the transcription of hormone/receptor specific target genes
What are the 2 functions of aldosterone?
- increases the reabsorption of Na+ by the kidney
- affects the plasma concentration of K+ and H+
What is an example of a glucocorticoid?
cortisol (humans), corticosterone (rodents)
Which steroid hormone has more of an effect on salt retention?
aldosterone > cortisol
How do glucocorticoids have an effect on protein and carbohydrate metabolism?
stimulate the synthesis of a number of gluconeogenic enzymes in hepatocytes, and several
enzymes that breakdown proteins in muscle and other tissues
What does cortisol do to gluconeogenesis and glucose oxidation?
gluconeogenesis: increased
glucose oxidation: decreased
Since glucocorticoids increase blood glucose levels, what happens to secreted insulin?
it increases
What is increased blood glucose due to excess of glucocorticoid activity known as?
adrenal diabetes
What happens if adrenal diabetes is prolonged?
it leads to true diabetes mellitus
What do glucocorticoids do to the levels of lipolytic enzymes in the adipose tissue cells?
they maintain or increase them
What does excess of glucocorticoids lead to in lipid metabolism?
hyperlipidemia and hypercholesterolemia
What do glucocorticoids do to
1. inflammatory responses
2. atrophy of the lymphatic system
3. circulating lymphocytes
4. antibody formation
5. histamine formation
- decrease
- increase
- decrease
- decrease
- decrease
What steroid hormone is used in organ transplantation?
glucocorticoids
Through the protein catabolic effect of glucocorticoids, what do they do to the protein matrix of bones?
they decrease it
What does glucocorticoids increase the loss of in bone which can lead to osteoporosis?
Ca++
What is ACTH synthesized as part of?
proopiomelanocortin (POMC)
What controls the feedback of cortisol secretion? (2)
hypothalamus and anterior pituitary
What happens to ACTH secretion in cases of enzyme deficiencies?
it is unchecked
What is caused due to enzyme deficiencies where cortisol is not produced?
congenital adrenal hyperplasia
What is the treatment for congenital adrenal hyperplasia?
administration of cortisol
Why is administration of cortisol used to treat congenital adrenal hyperplasia?
a) it corrects the deficiency
b) normalizes the ACTH secretion
What 2 membranes does ACTH bind to?
zona fasciculata and zona reticularis
What causes an increased production of cyclic AMP?
stimulation of adenylyl cyclase
What does cyclic AMP activate?
steroidogenic enzymes
What happens when steroidogenic enzymes are activated?
increase in synthesis and release of steroid hormones
When is the diurnal rhythm of ACTH and cortisol secretion at a minimum and maximum?
minimum: midnight
maximum: in the morning
What can the rhythm of plasma cortisol and ACTH be abolished by?
stress and Cushing’s disease
What does stress stimuli (physical or psychological) increase the synthesis and release of?
CRH, ACTH and cortisol
Why can the release of cortisol during stress be advantageous?
because it provides energy and amino acids through the breakdown of tissue proteins
Why can the release of cortisol during stress be disadvantageous?
because it can inhibit wound healing
Prolonged stress would maintain high levels of ___ which could lead to increased ___ ___, decreased ___ ___ and ___ ___
glucocorticoids, blood glucose, immune responses, bone loss
