Endocrine Flashcards
what is an endocrine hormone?
hormone released by gland into blood
what is a paracrine hormone?
hormone released by neighboring cell effecting neighboring cell
what is an autocrine hormone?
hormone made by that cell that acts on itself
what are some examples of polypeptide hormones?
ACTH
angiotensin II
calcitonin
glucagon
insulin
GH
PTH
ADH
What are some examples of steroid hormones?
Aldosterone
Cortisol
Calcitrol
estradiol
progesterone
testosterone
what are some examples of amine hormones?
epinephrine
norepinephrine
T4
T3
Melatonin
epinephrine is syn from which amino acid?
tyrosine
thyroid hormone (T3/4) are derived from?
tyrosine
what ion do you need to make thyroid hormone?
iodide
how are peptide hormones synthesized?
in inactive form as pre-prohormone
where are peptide hormones made?
RER
increase in what ion stimulates the release of peptide hormones?
Ca
how are steroid hormones made?
cholesterol
how are steroid hormones released?
biosynthetic pathway
–enzyme expression
–acute regulation via protein phosphorylation
all biosynthetic androgens have ___ carbons, a biosyn estrogens have ____ carbons
19, 18
what is the more potent form of testosterone called?
DHT
testosterone is the precursor to what other hormone?
17-b–estradiol
what is the rate limiting step of steroid hormone synthesis?
pregnenolone
what is the first step of steroid hormone syn?
cholesterol cleaved by CYP11A1 gene to convert cholesterol into pregnenolone
**stAR
how is stAR reguated?
protein phosphorylation
pregnenolone is the precursor for which hormones?
mineralocorticoids
glucocorticoids
Androgens
Estrogen
what is needed for gucocorticoid and androgen syn
P450c17
what are some characteristics of steroid hormones?
-lipid soluble
-carrier protein in blood
hours/days
intracellular receptor
receptor-hormone
what are some characteristics of peptide hormones?
water sol
no carrier protein
lasts mins in plasma
cell surface receptor
2nd messenger syst
what effect does the stroid hormone carrier protein have on the hormone?
influences potency and lifetime
where do steroid hormone receptors bind?
hormone response elements on DNA (increase or decrease transcription)
how is the equilibrium relationship of steroid hormone and receptorexpressed?
Kd
a steroid hormone with higher affinity will have what Kd?
lower Kd
less likely to dissociate from the carrier protein and enter the cell
What changes does carrier protein binding effect?
prolongs half life
buffers
controls potency
what happens if more free protein enters the cell?
more hormone is released from HP
on a nuclear receptor, activation domain 1 and 2 interact with:
co- repressors and co activators
on nuclear receptors DNA binding domain contains:
zinc fingers that interact with DNA
in the hormone binding domain what happens?
recognition of specific hormones biding induces dimerization
what are examples of hormones that use a tyrosine kinase receptor?
insulin, GH, PR
what are some examples of hormones that use G protein receptors?
cAMP, IP3, DAG/ Ca
apha is a _____
GTPase (inactive with GDP, active with GTP)
what are some key features of 2nd messenger systems?
-specificity
-amputation
augmentation
-rapid signal termination
what does alpha i do?
decrease adenylate cyclase, decreases cAMP
what does alpha q do?
stimulated phospholipase C, increase IP3, DAG, Ca2, PKC activated
what does alpha s do?
stimulates adenylate cyclase
increase cAMP, PKA activated
Which of the following is most likely to occur in hepatocytes, if the Gas subunit is constitutively active?
A. Decreased conversion of ATP to cAMP.
B. Inhibition of protein kinase A.
C. Increased glycogen synthesis.
D. Unregulated release of blood glucose.
E. Decreased glycogenolysis.
D. Unregulated release of blood glucose.
what are the steps for the DAG, Ca second messenger system?
–Hormone binding to the
receptor activates Gaq
–Gaq-GTP activates PLC
–PLC generates IP3 and DAG.
–IP3 binding to its receptor
causes release of Ca2+ from
ER
–DAG and Ca2+ activate protein kinase C
The IP3 Receptor is a _________ Calcium channel
Ligand Gated
____ binding causes the ____ receptor to open
IP3, IP3
(ca flows from ER to cytosol)
what are some examples of actions that trigger episodic hormone fluctuation?
sucking, food intake, exercise
what is an example of a pulsatile hormone?
lutinizing hormone
where do steroid hormones degrade?
outside of cell, dependent on lifetime of carrier-protein hormone complex
how are conjugated steroids excreted?
70% in urine
20% feces
how are peptide hormones degraded?
- Proteases in the blood
- Proteases in the cell surface
- Receptor-mediated endocytosis
what type of regulation occurs with steroid hormones
feedback inhibition
Big Concept: cortisol, thyroid hormone, sex
steroid hormones inhibit their production at the
level of the hypothalamus and anterior pituitary.
(Examples of long-feedback loop)
know this
what are the categories for hormone function?
1) utilization and storage of fuels; 2) maintenance of complex internal environment;
3) reproduction;
4) growth and development
Amines synthesized from tyrosine are:
epinephrine, norepinephrine; thyroxine/T4; triodothyronine/T3
are steroid hormones stored?
no
how are polypeptides and glycoproteins made?
synthesized from transcription and translation of genes
how are polypeptide hormones secreted?
inactive, as pre-pro-hormone, stored in membrane
Describe effects of plasma binding proteins on hormone levels and actions on target cells.
a. Steroid and steroid related proteins are bound to carrier proteins in the blood. The steroid carrier proteins buffer changes in blood steroid levels and modulate biological availability.
b. Some peptide hormones (like IGFs) are also bound to carrier proteins
what is the posterior pituitary called? why?
neurohypophysis- contains nerve termina endings whose cells ie in the hypothalamus
what is the anterior pituitary called?
adenophyopsisis
which part of the pituitary is considered a true endocrine gland?
anterior
what is the hypothalamus?
collection of neurons that synthesize and secrete peptide hormones in PUSATIE fashion
where do hypothalamic hormones act and how to they get there?
released to hypophyseal portal system and act on cells of the AP
what kind of hormones are released from the hypothalamus?
peptide
hypothalamic hormones are produced in and released from where?
neurons
how are peptide hormones produced in HTs?
An influx of Ca2+ through voltage-gated calcium channels
stimulates exocytosis of membrane vesicles containing
the peptide hormone
how are HP hormones released?
release from hypothalamic neurons is coordinated and
pulsatile TO HYPOSEA PORTA SYSTEM.
Hormones released into the hypophyseal portal system act on cells of the
anterior pituitary (adenohypophysis)
how are posterior pit hormones synthesized and reIeased?
- **OT and VP are synthesized in neuronal cell bodies in the hypothalamus (either paraventricular nuclei or supraoptic nucleus)
- **OT and VP are released from nerve terminal endings in the posterior pituitary.
what does oxytocin do?
**Uterine contractions
**Milk secretion
(mammary myoepithelia)
what does vasopressin do?
**Water resorption (kidney) ACTH release (AP)
**Vasoconstriction (vascular s.m.)
what are some other names for vasopressin?
- Antidiuretic Hormone (ADH)
- Vasopressin (VP)
- Arginine vasopressin (AVP)
what increases OT secretion?
ESTROGEN
suckling
cervical stretch
what is benefit of breast feeding after birth?
promotes uterine contractions to get placenta and other things out
what decreases OT secretion?
progesterone
what stimulates VP?
❑ >2% increase in osmolality of
ECF, (Osmoreceptors in the brain)
❑ >10-15% decrease in blood
volume (BP), Low pressure receptors in the left atrium of the heart
❑ Sensitivity to osmolality
increases with decreasing
blood volume.
what does VP do?
makes you retain water to add back to blood
what receptors does vasopressin trigger to hep retain water?
AQP2 (adds them to Lumina membrane, VP bind requires VP 2 receptor)
what happens in absence of VP?
AQP2 removed by endocytosis
what can occur with inadequate secretion or utilization of VP?
diabetes incipitus (excessive thirst and urination)
what are some genetic causes for issues with vasopressin?
➢ Neurogenic DI: vasopressin deficiency
❖Mutations in neurophysin II
➢ Nephrogenic DI: kidney resistant to vasopressin
❖Mutations in VP V2 receptor
❖Mutations in AQP2 channe
what are the two anterior pituitary hormones that can make direct changes to target organ?
Growth hormone and prolactin
CRH stimulates corticotropes to produce POMC and release its major product _____.
ACTH
GHRH (somatocrinin) stimulates
sommatotropes to release ____
GH
TRH stimulates thyrotropes
to release
TSH
GnRH stimulates gonadotropes to release _____
FSH and LH
GHRIH (somatostatin) inhibits
the release of ____
GH
what is the AP hormone that is under tonic inhibition from the hypothalamus? (what controls it)
prolactin (dopamine)
memorize hormone chart on side 309
put some in cards
What does ACTH act on and what does it do?
Adrenal Cortisol
Chronic stress
What does TSH act on and what does it do?
Thyroid, T3, T4
Energy production
(fuel metabolism, BMR)
What does LH, FSH act on and what does it do?
gonads (test/est/prog)
Reproduction
Sperm production
Ovulation, Menstrual Cycle
Pregnancy
What does GH and -GH act on and what does it do?
IGF-1
Increases: blood glucose,
lipolysis adipose (GH)
Cell Growth (GH, IGF1)
What does - GH act on and what does it do?
Mammary Gland
Milk production
what does Proopiomelanocortin (POMC) do?
an Anterior Pituitary Pro-Hormone also present in
Neurons, Melanocytes and Keratinocytes
corticotropes express what and what is their products?
Corticotropes express PC1
Products: ACTH, B-lipotropin
Corticotropes express _____ which contains ______
what does it do?
ACTH
a-MSH
✓ Stimulates cortisol synthesis in adrenal gland
✓ In excess, stimulates melanin production in melanocytes
Melanocytes and Keratinocytes express what?
a-MSH
✓ Stimulates melanin production via MC1 receptor
✓ Melanin produced provides protection from u.v. radiation
what is important about the glycoprotein family of anterior pit hormones?
- TSH, FSH, LH (pituitary basophils); hCG Placenta
- Two subunits +
- Both required for activity
- subunits same
- subunits confer specific biological function
what is significant about the growth/prolactin family?
- GH/PRL/hPL family similar structure and sequence identity
- GH most abundant pituitary hormone
- GH species specific
✓ GH from other non-primates no effect on humans (imp cause issues with it cant be supplemented by other animas)
what is the most abundant AP hormone?
GH
Describe the relationship between pro-opiomelanocortin (POMC) and the hormones derived from it.
- POMC is the prohormone for ACTH, a-melanocyte stimulating hormone (a-MSH). ACTH contains amino acids encoding a-MSH which stimulates melanin production in melanocytes and can lead to hyperpigmentation of the skin.
what stimulates GH release?
- Hypoglycemia
- Decreased FA’s
- AA’s (arginine)
- Exercise
- Sleep Stages
- Estradiol
- Required (thyroid hormone
if you are conceted a patient has not enough GH how can you test?
give sugar drink and see what happens
what conditions inhibit GH release?
- Hyperglycemia
- Elevated FA’s
- IGF-1
how does IGF get through ECF?
on binding protein, not free fIoat, this ensured targeted delivery of free igf to igf receptors
- _____ is the major source
of IGF-1 in the blood.
Liver
what stim growth in bone?
GH and locally produced IGF-1 stimulate growth in bone
______ stimulates prechondrocyte in germinal zone to differentiate into chondrocytes and secrete _____
GH, IGF-1
what stim chondrocytes to proliferate?
Local IGF-1 stimulates
chondrocytes to proliferate
what prevents growth in long bones?
epiphyseal pate closure
somatostatin is stimulated by
glucose and fatty acids
GH stimulates_____ synthesis
and secretion.
IGF-1
_____ is the main
source of IGF-1 in the blood
Liver
IGF-1 inhibits ____
GH release
what stimuates somatocrinin or GHRH?
Stress*
Exercise
Sleep stages
Decreased glucose
Increased a.a.’s
Which hormone could restore growth when the GH receptor does not respond to GH?
IGF-1
too much GH in aduts causes
acromegaly (enarged tounge
Which hormones are peptide hormones synthesized in cell bodies in the hypothalamus; released from nerve terminal endings in the posterior pituitary
Oxytocin and vasopressin
oxytocin:
stimulates uterine contractions during parturition and contraction of myoepithelia and milk ejection during lactation. Release stimulated by suckling, “let down” reflex, cervical stretch from uterine contraction (positive feedback loop).
Estrogen stimulates OT release; progesterone inhibits OT release
vasopressin: adh or antiduretic hormone:
Humans require arginine vasopressin.
ADH decreases osmolality of the ECF by increasing water resorption in the kidney by
stimulating Vasopressin V2 GPCR receptors, increase in cAMP/PKA and increase in insertion of aquaporin 2 channels into the luminal plasma membrane of kidney collecting duct cells. Stimuli: ≥2% increase in osmolality (i.e. NaCl) of ECF, ≥10%
decrease in BP. Sensitivity to osmolality increases with decreased BP.
Diabetes incipidus is caused by
inadequate production or utilization of ADH
neurogenic DI is caused by
vasopressin deficiency, mutations in neurophysin 2 part of ADH prohormone; Nephrogenic DI kidney resistant to ADH, causes mutations in either vasopressin V2 receptor or the AQP2 channel.
Hypothalamic hormones are ____ released from neurons in coordinated ____
secretion pattern
peptide, pulsatile
TSH (AP): stimulates
what inhibits this?
thyroid gland to produce T3/T4 which increase fuel metabolism
and basal metabolic rate (BMR). Feedback inhibited by T3.
- ACTH (AP): stimulates
what inhibits this?
the adrenal gland to produce cortisol which raises blood
glucose. Feedback inhibited by cortisol.
- FSH/LH (AP): stimulates
what inhibits?
estradiol/testosterone production in ovary and testes. LH stimulates progesterone in ovary. Feedback inhibited by estradiol
GH stimulates lipolysis of TGs in adipose and release of insulin like growth factor 1 (IGF1), it inhibits glucose uptake in muscle. Together GH and IGF1 promote growth in all tissues. GH release is stimulated by low blood glucose via somatocrinin release from the hypothalamus
what are the effects of thyroid hormone in adults?
- Increase BMR
- Increase O2 consumption
- Increase cardiac output
- Stimulates metabolism of fat, carb. and proteins
- Induces many enzymes
what does thyroid hormone do in children?
- Growth and maturation of skeletal bone
- Vital for development of the CNS
– Deficiency, untreated immediately after birth, leads to
irreversible brain damage.
thyroid hormone is derived from
tyrosine and iodide
TSH stimulates synthesis of:
T3 and T4
what transports iodide into the lumen?
pendrin
thyroid hormone synthesis requires?
thyroglobulin and iodide
how can iodide be transported against its electrochemical gradient
Na/I symporter
____________ incorporates I- into Tyr on intact Tgb to form DIT
Thyroid peroxidase
Thyroid peroxidase couples
two _____ to make _____
DIT to make T4 on Tgb
what is one difference between T3 and T4?
T4 is not as potent as T3
what is tertiary hypothyroidism
defect in hypothalamus
what is secondary hypothyroidism?
defect in pituitary
what is primary hypothyroidism?
defect in thyroid gland
Predict the TSH and T3/T4 levels for Primary Hypothyroidism
TSH: high
T3/4: low
Predict the TSH and T3/T4 levels for Secondary Hypothyroidism
TSH: low
T3/4: low
Predict the TSH and T3/T4 levels for Tertiary Hypothyroidism
TSH: low
T3/4: low
what does TRH test measure?
increase in pituitary TSH
in a 1* hypothyroidism TRH dependent stimulation testing what is the result?
TSH elevated before TRH;
normal pituitary response
in a 2* hypothyroidism TRH dependent stimulation testing what is the result?
TSH suppressed/undetectable;
no pituitary response.
in a 3* hypothyroidism TRH dependent stimulation testing what is the result?
delayed TSH pituitary response
Name possible causes for primary hypothyroidism
iodide def
def of thyroid peroxidase
what is the Rate-limiting step of adrena cortica steroid hormones?
cholesterol to pregnenolone
catalyzed by p450scc,
regulated by STAR
VERY IMP
________________________is required for synthesis of cortisol and DHEA
p450c17 hydroxylase lyase
_______ is required for synthesis of aldosterone and cortisol
p450c21
what can happen with a p450c21 deficiency?
- impaired aldosterone and cortisol synthesis
- elevated DHEA
Glucocorticoids named for ?
their ability to raise blood glucose
In absence of cortisol, even short periods of fasting result in ___________
catastrophic hypoglycemia
In liver, cortisol:
- Stimulates GN
- Stimulates glycogen synthesis
Glycerol used by liver as a precursor for
gluconeogenesis
In adipose:
Cortisol stimulates
lipolysis of TGs
In muscle, cortisol:
- Stimulates protein degradation
- Decreases glucose uptake
what is the chain of rxn for cortisol release?
CRH, ACTH, cortisol from adrenal gland
what does cortisol inhibit?
CRH and ACTH
Primary hypocortisolism causes increase or decrease in what?
ACTH: high
Cor: ow
hypercortisoism from oray administed cortiso causes what change?
inc cort
dec ATCH
what happens with cushing syndrome?
weight gain, rounding face, muscle weakness, thin fragile skin, high BP (cause corto)
what does Aldosterone do?
Stimulates Na+ resorption and
K+ excretion
what triggers synthesis of Aldosterone?
✓ Angiotensin (AII)
✓ Elevated K+ in ECF.
What does RAAS do?
Increases Na+ & BP, Decreases K+
what activates RAAS?
K+, decrease in BP, Na+ levels
ANG II stimuates:
✓ Increases BP
✓ Stimulates aldosterone
synthesis/release
✓ Stimulates ADH release
- Aldosterone stimulates
✓ Na+ resorption, K+ excretion
* Low BP stimulates renin release
from kidney
* Renin converts Angiotensinogen to A-I
* ACE converts A-I to A-II K+
what is Addison’s disease?
adrenal insufficiency
causes weakness, dec BP, dec bood sugar
what are eicosanoids?
–Derived from essential fatty
acids: w6, linoleic acid & w3,
linolenic acid.
–Regulate inflammatory response, smooth muscle contraction, hemostasis
Linoleic acid is converted to ______ and stored in phospholipid membranes
arachidonic acid (AA)
PLA2 activity is decreased by
glucocorticoids
(inc by cytosol Ca and protein kinase C)
Cyclo-oxygenase converts AA into
PGH2 a precursor for:
prostaglandins and thromboxanes (TXA2).
Cyclo-oxygenase is inhibited by:
- Irreversibly inhibited by aspirin
- Reversibly inhibited by non-
steroidal anti-inflammatory
drugs (NSAIDs)
____ converts AA into
PGH2 a precursor for prostaglandins
and thromboxanes (TXA2)
Cyclo-oxygenase
Aspirin as an ________
anti-thrombotic agent.
Thromboxanes DO WHAT?
increase platelet
aggregation; are synthesized by
platelets. (platelets lack nuclei and cannot make new proteins)
Prostacyclin (PGI2) DOES WHAT?
decreases platelet aggregation; is synthesized by endothelial cells of blood vessels
aspirin irreversibly inhibits?
COX
