Endocrinology Flashcards
what is homeostasis
maintenance of a stable internal environment for normal body functioning
T/F homeostasis is a state of static equilibrium
F; dynamic equilibrium
what is homeostatic imbalance
disturbance in homeostasis resulting in stress or disease
control of the internal environment relies on:
1. constant monitoring of
2. responding to
- constant monitoring of the composition of blood
- changes in blood composition
most systems operate in what feedback manner
negative
how does the body communicate with cells and tissues
NTs and hormones
endocrine systems can have a rapid or slow response time, ranging from
minutes to months
define endocrine glands
any tissue which releases hormones into the bloodstream to effect change in another tissue
what hormones fall under amino acid derivatives
epinephrine; thyroxine; melatonin
what hormones fall under peptides
hypothalamic hormones; insulin
what hormones fall under proteins
growth hormone; prolactin
what hormones fall under steroids
glucocorticoids; mineralocorticoids; gonadal steroids
only one category of hormones is synthesized on demand, which is
steroids
which hormone category(s) diffuses from the cell
steroids and thyroid hormone
the fact that steroids and thyroid hormone diffuses from the cell has what 2 implications
bound to carrier protein in plasma; long half-life
what are 4 causes to disturbed homeostasis
overproduction, underproduction, transport/clearance problems, resistance
what is unique about the receptor for steroids and thyroid hormone
found in the cytoplasm/nucleus
all hormones except for ___________ and __________ use ________________
steroid; thyroid; second messenger systems
what are the 2 types of GPCRs
adenylate cyclase-cAMP
phospholipase C-Ca
what is an example of a hormone that uses adenylate-cyclase-cAMP
β-adrenergic receptors for NE/E
what is an example of a hormone that uses phospholipase C-Ca
α1-adrenergic receptors for NE/E
what is an example of a hormone that uses tyrosine kinase
insulin
what is an example of a hormone that uses the cytokine second messenger system (i.e. JAK/STAT)
growth hormone
steroid/thyroid hormone receptors have what domains
hormone binding domain and DNA binding domain (which binds to HRE)
how does the thyroid hormone receptor differ from the steroid hormone receptor
the thyroid hormone receptor is already bound to the HRE; it gets to the nucleus via a binding protein; the receptor is a heterodimer (with RXR)
T/F there is a stepwise increase in signal from hypothalamus -> pituitary -> target tissue
T
what is another name for dopamine
prolactin inhibiting hormone; PIH
CRH regulates the secretion of what two hormones
ACTH and MSH
what is another name for somatostatin
growth hormone inhibiting hormone; GHIH
what hormones are released by the posterior pituitary
ADH and oxytocin (vasopressin)
the anterior pituitary is also called the pars ______________; the posterior pituitary is also called the pars _____________.
distalis; nervosa
what region of the pituitary mainly secretes MSH
pars intermedia
what connects the hypothalamus and pituitary? what partially enwraps it
infundibulum; pars tuberalis
oxytocin is produced by ___________ neurosecretory cells within the _________________ nucleus
magnocellular; paraventricular
ADH is produced by _____________ neurosecretory cells within the _________________ nucleus
magnocellular; supraoptic
AP-hormone regulating hormones are produced by _____________ cells within the _________________ and ________________ nuclei
parvocellular; supraoptic and paraventricular
what are the 3 main endocrine cells of the AP
acidophils, basophils, chromophobes
acidophils includes (2)
lactotropes (prolactin) and somatotropes (GH)
basophils includes (3)
thyrotropes (TSH), gonadotropes (LH/FSH), corticotropes (ACTH)
chromophobes includes (1)
melanotropes (MSH); within the pars intermedia
MSH is stimulated by ___________ and inhibited by __________
stimulated by CRH; inhibited by oxytocin
prohormones are processed to active hormones _________ secretion whereas prehormones are processed to active hormones ___________ secretion
before; after
examples of prehormones
vitamin D3 is converted to 1,25 dihydroxyvitamin D3 in target tissue
thyroxine (T4) is converted to T3 in target tissue
how is POMC processed in the AP
to ACTH and β-LPH
POMC can give rise to (4)
ACTH, MSH, lipotropin (LPH), endorphin
how is POMC processed in the pars intermedia
to ACTH and β-LPH; then further to MSH, CLIP, γ-LHP, β-endorphin
what is responsible for cleavage of POMC into different products
prohormone convertase 1, 2, 3
describe MSH signalling
α-MSH binds to MC1-R (GPCR, adenylate cyclase-cAMP); triggers cell proliferation and melanin synthesis in melanocytes and hair follicles; has anti-inflammatory effects in immune cells
T/F MC1-R can bind to ACTH at high concentrations, which reduces skin pigmentation
F; it causes hyperpigmentation when this happens
what melanocortin receptor binds only ACTH
MC2-R
MC3-R binds
all MSH and ACTH equally
MC3-R is involved in
energy homeostasis, anti-inflammatory effects in alveolar macrophages
MC4-R binds
primarily α-MSH, but also all MSH and ACTH
MC4-R is involved in
inhibition of feeding behaviour and appetite (in the CNS)
MC5-R binds
ACTH and α-MSH
MC5-R is involved in
embryogenesis and exocrine gland activity
what is the most abundant AP hormone
GH
GH characteristics:
- (protein/amine/peptide/steroid) hormone
- binds to ____________ receptor
- mostly transported (free/via binding protein)
- synthesized, stored and secreted by __________________ in the _________
- half-life is
- protein
- cytokine (JAK/STAT)
- via binding protein (GHBP)
- somatotropes; AP
- 6-20 min
GHRH is released by (parvocellular or magnocellular) cells in the (PVN or SN)
parvocellular; PVN
The largest GH peak occurs
1h after onset of sleep
Describe the pattern of GH secretion throughout life
highest basal levels early in life; highest frequency/amplitude during puberty
hypoglycemia _______ GH secretion; hyperglycemia __________ GH secretion
increases; decreases
ghrelin_____ GH secretion
increases
IGF characteristics:
- (protein/peptide/steroid/amine)
- binds to ____________ receptor
- mostly transported (free/via binding protein)
- produced in the
- half-life is
- protein/peptide
- tyrosine kinase
- binding protein (IGFBP)
- liver
- ~12h
IGF-1 is prominent during ______________ whereas IGF-2 is prominent during
sexual maturity; embryonic/fetal growth (with insulin)
IGF-1 acts via what route
endocrine, paracrine and autocrine
T/F GH stimulates the synthesis and release of IGF-1 only in the liver
F; it occurs in many tissues
in what instances to GH and IGF-1 exert the same effect
increase amino acid uptake and protein synthesis; increase bone growth and mineralization
T/F GH can cross-react with prolactin receptor
T
what does it mean for GH to be a diabetogenic factor
opposes actions of insulin on carbohydrate and lipid homeostasis (decreases tissue sensitivity to insulin)
T/F rBST is allowed for use in dairy cows in both the US and Canada
F; allowed in the US but not in Canada
What can be used to promote growth in livestock in the EU
nothing
T/F it is unclear if growth promoters in milk or beef impact human health
T
pre-sexual maturity, underproduction of GH causes ______________, reduced sensitivity causes _____________ and overproduction causes ___________
dwarfism; pygmy; gigantism
gigantism is typically caused by
a tumor on the anterior pituitary
post-sexual maturity, underproduction/reduced sensitivity of GH is associated with ___________ and __________, whereas overproduction causes _____________
alopecia; Cushings; acromegaly
what is typically the first sign of acromegaly
diabetes mellitus (excessive release of glucose and inhibition of glucose utilization)
in >90% of acromegaly patients, the disease is caused by
a benign pituitary tumor
what can explain the variation in dog breeds
mutations in IGF-1
Receptors for:
TRH:
TSH:
T4:
T3:
TRH: GPCR (Gq aka IP3/DAG)
TSH: GPCR (Gs and Gq)
T4: NR
T3: NR
thyroxine refers to
T4
the isthmus is indistinct in
dogs and cats
what is the largest purely endocrine gland
thyroid
how many parathyroid glands are there
2 on each lobe; 4 total
is more T4 or T3 produced
more T4
what is the role of follicular cells
uptake of iodide from blood vessels via Na/I symporter and pumping into the lumen via I channel
what is the role of colloid
contains thyroglobulin and enzymes to make T3 and T4
thyroglobulin is produced in
thyrocytes (then secreted into colloid)
what are the roles of TPO
- converts iodide to iodine
- adds iodine to tyrosine residues on thyroglobulin to produce monoiodotyrosine (MIT) or diiodotyrosine (DIT)
- condenses MIT and DIT to form T3 and T4
TSH stimulation induces follicle cells to
endocytose thyroglobulin and hydrolyze the bound T3 and T4; secrete the hormones into the blood
how is thyroid hormone transported in the blood; does it have a higher affinity for T4 or T3
via thyroxine-binding globulin (TBG), which has a higher affinity for T4
T/F there is evidence of seasonal and circadian TRH secretion
T
what is the Wolff-Chaikoff effect
excess iodide inhibits iodide trapping regardless of TSH levels; prevents hyperthyroidism
what is the ratio of T4:T3 secretion; what is the ratio of T4:T3 in plasma; elevated T3 indicates
4:1; 20:1; hyperthyroidism
how does T4 become T3 and where
deiodinases convert in the kidneys and liver mainly
T/F only free T3/T4 are biologically active
T
the half-life of T4 is and the half-life of T3 is
6-7 days; 1 day
thyroid hormone increases synthesis of
GH and glucocorticoids
95% of thyroid disease is (primary/secondary/tertiary); in dogs it is commonly due to _____________ whereas in cats it is commonly due to ____________
primary; immune-mediated (dogs) or idiopathic atrophy (cats)
what are common causes of primary hyperthyroidism in cats and in dogs? what about secondary hyperthyroidism? what autoimmune disease can cause hyperthyroidism?
cats: thyroid adenoma
dogs: thyroid carcinoma
secondary: pituitary adenoma
grave’s disease (antibodies mimic TSH)
what is a consideration with euthyroid sick syndrome
no benefit to supplementing with T4, since the issue has to do with conversion of T4 to T3
what drug can be used to treat hyperthyroidism
methimazole
99% of calcium is stored in ______ as _____________; 0.9% is found _______________ and 0.1% is found _____________
bones; hydroxyapatite; intracellularly; extracellularly
50% of extracellular Ca is ____________; 40% is _____________ and 10% is __________________
ionized (free); protein-bound; with PO4 and citrate
intracellular Ca is associated with membranes in
mitochondria, ER and PM
intake of calcium
entirely through diet (1/3 absorbed in SI)
what is the role of PTH in the intestines, kidneys and bone
intestines: no direct effect
kidney: stimulates Ca reabsorption and inhibits PO4 reabsorption
bone: stimulates resorption
what is the role of 1,25 dihydroxyvitamin D3 in the intestines, kidneys, and bone
intestines: stimulates absorption of Ca and PO4
kidney: stimulates reabsorption of Ca and PO4
bone: stimulates resoprtion
what is the role of calcitonin in the intestines, kidneys and bone
intestines: none
kidney: inhibits reabsorption of Ca and PO4
bone: inhibits resorption
PTH is released by _________ cells in the ___________ gland when serum Ca is _____
Chief; parathyroid; low
T/F PTH stimulates the kidneys to make the enzyme needed to convert vitamin D3 to 1,25 dihydroxyvitamin D3
T; (it is called 1α hydroxylase)
parathyroid cells that detect Ca (CaSR) use ___________ signalling
PTH uses ___________ receptors
GPCR Gs (adenylate cyclase)
GPCR (called PTHR1)
T/F PTH is stored and released when needed
F; never stored
PTH stimulates _____________ to __________ bone
osteoclasts; reabsorb
Ca reabsorption takes place in what part of the kidney
distal tubule
what channel is regulated by PTH to reabsorb Ca in the kidney
TRPV5
T/F dogs and cats can synthesize vitamin D3 from 7-dehydrocholestrol with UV light in skin
F; can only obtain from diet
in the liver, vitamin D3 is converted to ______________
in the kidney, it is converted to _______________ due to the action of _________________ (which is stimulated by PTH)
25-hydroxyvitamin D3; 1,25-dihydroxyvitamin D3; 1α hydroxylase
cholecalciferol is another name for
Vitamin D3
the primary mechanism used by 1,25-dihydroxyvitamin D3 is _________________
active reabsorption of Ca and PO4 from the intestines when Ca is low
when the diet is Ca deficient, 1,25-dihydroxyvitamin D3 stimulates
production of more osteoclasts
increased calcitriol (1,25-dihydroxyvitamin D3) ________________ PTH secretion
reduces
calcitonin is released by ______________ cells when Ca levels are ________
parafollicular cells; high
T/F calcitonin is a peptide that is stored until needed
T
what is the normal ratio of Ca:P in the blood
1-2:1
feed that has a low Ca:P ratio causes
increased PTH secretion
glucocorticoids oppose _____________ action in the ___________
Vitamin D action in the GI tract
why does hyperparathyroidism cause polyuria/polydipsia
high Ca blocks ADH effects
primary hyperparathyroidism is (common/rare) in dogs and cats, but _________ are a genetically predisposed breed
rare; Keeshonds
kidney failure and vitamin D deficiency can cause
secondary hyperparathyroidism
what is important to check when diagnosing hyperparathyroidism
kidney values for CKD
clinical signs of hypoparathyroidism are _______calcemia and _____phosphatemia
hypocalcemia; hyperphosphatemia
calcium and vitamin D deficiency in young animals causes ____________, and ____________ in older animals
rickets; osteomalacia
what percentage of cows get subclinical milk fever and what percent will get clinical
60%; 3-10%
CRH is a ________ hormone that uses ____________ receptor; ACTH is a _________ hormone that uses ___________ receptor
peptide; GPCR (Gs) for both
ACTH receptors are on what regions of the adrenal gland
zona fasciculata and zona reticularis of the adrenal cortex
T/F aldosterone is under the control of ACTH
F
the name for the ACTH receptor is
MC2-R
the primary and secondary actions of ACTH are
secretion of glucocorticoids; secretion of sex steroids
what is a phamacological target for pituitary adenomas
SSTR5
the adrenal cortex arises from what embryological tissue? what about the medulla?
mesoderm; neural crest ectoderm
mineralcorticoids regulate
Na/K balance at the kidneys
what is the starting material for production of steroids
cholesterol
all steroid production starts with conversion of ___________ to ___________
cholesterol; pregnenolone
what is the rate limiting step in steroidogenesis
movement of cholesterol into the mitochondria
what moves cholesterol to the inner mitochondrial membrane? what stimulates it’s insertion?
StAR protein (in conjunction with PBR); ACTH (via cAMP)
what converts cholesterol to pregnenolone
side chain of P450 enzyme
StAR is located on the _______ mitochondrial membrane whereas PBR is located on the ________ mitochondrial membrane
outer; inner
what are the two steroid transport proteins
albumin (25%)
transcortin (75%)
T/F mineralocorticoids have transport proteins
F
T/F cortisol stimulates glycolysis
F; it stimulates gluconeogenesis
T/F cortisol recruits glucose from non-CHO sources
T
how does cortisol dampen the inflammatory response
decreases cytokine production; inhibits chemoattraction; decreases production of some immune cells
what triggers release of cortisol (broadly)
chronic, low-grade stress; hypoglycemia
what is the role of adrenal androgens
normal physiology in females; secondary sex characteristics in males and females
how would clinical signs differ between primary and secondary hypoadrenocorticism
primary: hyposecretion of all corticosteroids, including mineralocorticoids
secondary: hyposecretion of cortisol and sex androgens due to hyposecretion of ACTH
primary hypoadrenocorticism is called
Addisons disease
adrenal disease is a common cause of hyperadrenocorticism in
ferrets
most hyperadrenocorticism cases are
secondary (ACTH oversecreting pituitary tumour)
the most common cause of hyperadrenocortisim is
administering exogenous glucocorticoids (iatrogenic)
in horses, ACTH oversecretion is usually due to
Pituitary pars intermedia dysfunction (PPID)
what is the effect of aldosterone on the kidney
increase Na reabsorption and decrease K reabsorption
what is the goal of aldosterone
maintain Na/K homeostasis and blood volume
what is the effect of ADH on the kidney
increase H2O reabsorption
what is the goal of ADH
maintain blood osmolality
what hormone inhibits Na reabsorption and acts to decrease blood volume
ANP
high K does what to the adrenal cortex
depolarizes cells of zona glomerulosa -> aldosterone secretion
aldosterone puts what receptors in the DT/CD
ENaC and Na/K ATPases
low Na does what to the adrenal cortex
low Na -> release of renin by juxtaglomerular apparatus -> renin produces angiotensin II -> angiotensin II stimulates the release of aldosterone
ADH is released with as little as a ___% increase in
1%
ADH uses what receptor type
Gs (cAMP)
ANP inhibits
ENaC and Na/K ATPase
hyperaldosteronism is typically
primary (bilateral hyperplasia or neoplasia of the zona glomerulosa)
what can be used to treat diabetes insipidus
desmopressin
diabetes insipidus can be caused by:
central:
nephrogenic:
lack of ADH from pituitary; reduced ability of kidneys to respond to ADH
effects of NE/E from medulla last ____________ than NE/E within nervous system
10x longer
what cell type produces NE/E in the medulla
Chromaffin
T/F cortisol release assists with NE/E synthesis
T
a rare tumour that secretes NE/E is called
pheochromocytoma
the brain uses ___% of glucose at rest
60%
what produces insulin/glucagon/somatostatin
pancreatic islets
α cells:
β cells:
δ cells:
glucagon; insulin; somatostatin
where is insulin cleaved
golgi
how is glucose released and what is it dependent on
dependent on Ca
- in presence of ATP, K+ channels close and depolarize the cell
- Ca channels open and mediate fusion of secretory vesicles (containing insulin) with the membrane
insulin uses a _____________ receptor
tyrosine kinase
what are target tissues for insulin
liver, adipose, skeletal muscle
in the presence of glucose, what inhibits glucagon release
insulin and somatostatin (GHIH)
as a primary action, glucagon binds to ___________ receptors in the______________ to stimulate ____________
GPCR; liver; glycogenolysis and gluconeogenesis
what other functions are mediated by glucagon (besides gluconeogenesis and glycogenolysis in the liver)
lipolysis, protein catabolism, ketogenesis
pancreatitis is associated with
premature activation of pancreatic enzymes
pancreatitis and diabetes mellitus is rare in
horses and cattle
what is one endocrine-related risk factor for pancreatitis
hyperadrenocorticism
Type I diabetes:
Type II diabetes:
insufficient insulin; insulin resistance
causes of Type I diabetes in dogs are _________________ in cats ______________; type II can be caused by ___________________ or _________________ treatment
immune-mediated or post-pancreatitis; amyloidosis; hyperadrenocorticism; glucocorticoids
measurement of serum _____________ can differentiate between diabetes mellitus and stress-induced hyperglycemia
fructosamine
hyperglycemia may be caused by what physical insult
traumatic/severe injury (can be prognostic in dogs but not cats)
insulinoma is ___________ and is common in _____________
increased insulin secretion due to a beta-cell tumor; ferrets
