Lec 23 Endocrine Intro Flashcards
Is set point constant across stimuli?
No - it is specific for particular stimuli and particular situations
What did Charles Edouard Brown Sequard show
concept of hormonal action
3 functions of endocrine system
- homeostasis
- growth and development
- reproduction
Where are neuropeptides synthesized?
in nerve cell body
Where do hypothalamic neuropeptides go/target?
- into vessels of hypothalamic-pituitary portal system
- transported to target cells in anterior pituitary
- tells anterior pituitary to make/secrete its hormones
What are trophs?
endocrine cells of anterior pituitary
What do lactotrophs secrete?
prolactin
what do somatotrophs secrete?
growth hormone
what do corticotrophs secrete?
ACTH
What do thyrotrophs secrete?
TSH
Where do posterior pituitary hormones come from?
- they are made in hypothalamus and stored in bulbous nerve terminals in posterior pituitary
what hormones are made in posterior pituitary?
none
What 2 hormones are secreted via posterior pituitary?
vasopressin [ADH]
oxytocin
If you took out the pituitary would you still be able to secrete vasopressin?
yes!
What are 3 classes of hormones
- polypeptides
- amino acid derivatives
- thyroid hormones and steroids
Are polypeptide hormones lipid soluble? where is receptor located on/in cell? example?
- not lipid soluble
- bind to receptors on surface of target cell
- ex: pituitary hormones
Are amino acid derivative hormones lipid soluble? where is receptor located on/in cell? example?
- most are not lipid soluble
- bind to receptors on surface of target cell
- ex. epinephrine
Are thyroid hormones lipid soluble? where is receptor located on/in cell?
- YES! they act like steroid hormones
- bind to receptor inside target cell
Are steroid hormones lipid soluble? where is receptor located on/in cell? example?
- they are lipid soluble
- bind to receptors inside target cell
- ex. cortisol
6 peptide hormones secreted by anterior pituitary?
- LH: luteinizing hormone
- FSH: follicle stimulating hormone
- GH: growth hormone
- prolactin
- TSH: thyroid stimulating hormone
- ACTH: adrenocorticotropic hormone
What organ do LH and FSH target? What effect on target?
ovary/testes
- FSH causes ovary to secrete estrogen
- LH causes testes to secrete testosterone
What organ does prolactin target? What effect on target?
breasts
- causes lactation [make milk]
What organ does GH target? What effect on target?
liver
- causes liver to secrete IGF-1 [insulin like growth factor 1]
What organ does TSH target? What effect on target?
thyroid
- causes thryoid to secrete thyroxine [T4]
What organ does ACTH target? What effect on target?
adrenal glands
- causes adrenals to secrete cortisol
What organ does ADH target? What effect on target?
kidney
- antidiuretic, causes reabsorption of water in kidney
What is effect of estrogen on FSH?
turns off FSH = negative feedback
What is effect of testosterone on LH?
turns off LH = negative feedback
What is effect of thyroxine on TSH?
turns off TSH = negative feedback
Which of the pituitary hormones do not have negative feedback from their target organs?
- only prolactin
What kind of feedback loop in prolactin?
- sucking on breast increases prolactin secretion
= positive feedback
What stimulates TSH secretion from AP?
TRH from hypothalamus
What stimulates ACTH from AP?
CRH from hypothalamus
What stimulates LH from AP?
GnRH from hypothalamus
What stimulates FSH from AP?
GnRH from hypothalamus
What does somatostatin do to anterior pituitary? where does it come from?
- released from hypothalamus
- inhibits anterior pituitary secretion of growth hormone
What does dopamine do to anterior pituitary? where does it come from?
released from hypothalamus
inhibits prolactin secretion
What are the 4 trophic releasing hormones from the hypothalamus and their targets
1 TRH –> TSH
2 CRH –> ACTH
3 GnRH –> LH + FSH
4 GHRH –> GH
What makes a cell a target cell?
specific receptors for the hormone
What causes down regulation/up regulation?
- receptor number on target cell
- affinity of target cell receptor for hormone
Severed stock experiment – continuous vs pulsatile? what explains this
- continuous infusion of GnRH down regulates LH/FSH
- pulsatile infusion increases LH/FSH
- with continuos infusion you are continuously having GnRH bound which when bound brings the receptor into cell and degraded. so in contuous activation you are degrading the receptors and lowering the number = down regulation
When is cortisol highest? lowest?
- highest in AM
- lowest in PM
When is growth hormone highest?
peak at night, within an hour of sleepish
lower during day time
What does testosterone peak?
morning
What is relation GH and insulin?
GH is counter-regulatory to insulin
Is major hypothalamic control of prolactin stimulatory or inhibitory? by what?
inhibitory – by dopamine
What is relation GH and somatostatin?
somatostatin from hypothalamus inhibits GH from AP
What are 2 effects of growth hormone
- direct action on metabolism
- stimulation IGF-1 from liver
What other hormone is in same family as growth hormone?
prolactin
What is shared in prolactin/GH family? type of Receptor?
- dimer receptor
- tyrosine kinase associated receptor
- activates Jak/stat pathway in cell
What is different insulin receptor vs growth hormone receptor
- insulin receptor: 2 beta subunits bound 2 alpha subunits bound to each other, tyrosine kinase is part of the receptor
- growth hormone receptor: 2 separate subunits
What types of hormones use JAK-STAT signaling pathway?
- growth hormone
- prolactin
- erythropoietin
- thrombopoietin
What is characteristic of jak/stat signalling pathway
- 2 separate pieces of receptor
- jak binds both receptor and Stat = signal transducer
- stat transduces signal into nucleus
Where does grhelin come from? where does it act [2 things]?
comes from stomach
- stimulates GH
- feedback to NPY [feed me] neurons from hypothalamus
3 Direct actions of GH hormone
- increase gluconeogensis in liver
- increase lypolysis
- causes liver to secrete IGF1
What are 4 [2 things, 2 hormones] positive stimuli of GH?
- puberty
- working out
- GHRH
- Ghrelin
What are 3 [2 things, 1 hormone] neg stimuli of GH?
obesity
senescence
somatostatin [SRIF]
what does IGF1 do?
- growth factor for muscle
- major growth factor for bone and strength
- —- activates osteoblasts, blocks osteoclasts
How do GH and IFG-1 work together?
GH mobilizes substrate [sugar, fat, protein via lypolysis, gluconeogenesis]
IGF-1 incorporates it for growth
What makes a cell a target cell?
specific receptors for the hormone
What causes down regulation/up regulation?
- receptor number on target cell
- affinity of target cell receptor for hormone
Severed stock experiment – continuous vs pulsatile? what explains this
- continuous infusion of GnRH down regulates LH/FSH
- pulsatile infusion increases LH/FSH
- with continuos infusion you are continuously having GnRH bound which when bound brings the receptor into cell and degraded. so in contuous activation you are degrading the receptors and lowering the number = down regulation
When is cortisol highest? lowest?
- highest in AM
- lowest in PM
When is growth hormone highest?
peak at night, within an hour of sleepish
lower during day time
What does testosterone peak?
morning
What is relation GH and insulin?
GH is counter-regulatory to insulin
What does HCG do?
- stimulates TSH receptor on thyroid [taking place of TSH] so you get more T3/T4 but low TSH
- hyperthyroidism
- in pregnancy
What is relation GH and somatostatin?
somatostatin from hypothalamus inhibits GH from AP
What are 2 effects of growth hormone
- direct action on metabolism
- stimulation IGF-1 from liver
What other hormone is in same family as growth hormone?
prolactin
What is shared in prolactin/GH family? type of Receptor?
- dimer receptor
- tyrosine kinase associated receptor
- activates Jak/stat pathway in cell
What is different insulin receptor vs growth hormone receptor
- insulin receptor: 2 beta subunits bound 2 alpha subunits bound to each other, tyrosine kinase is part of the receptor
- growth hormone receptor: 2 separate subunits
What types of hormones use JAK-STAT signaling pathway?
- growth hormone
- prolactin
- erythropoietin
- thrombopoietin
What is characteristic of jak/stat signalling pathway
- 2 separate pieces of receptor
- jak binds both receptor and Stat = signal transducer
- stat transduces signal into nucleus
Where does grhelin come from? where does it act [2 things]?
comes from stomach
- stimulates GH
- feedback to NPY [feed me] neurons from hypothalamus
3 Direct actions of GH hormone
- increase gluconeogensis in liver
- increase lypolysis
- causes liver to secrete IGF1
What are 2 positive stimuli of GH?
- puberty
- working out
What are 2 neg stimuli of GH?
obesity
senescence
what does IGF1 do?
growth factor for muscle binds binding proteins in circulation major growth factor for bone and strength act to activate osteoblasts blocks osteoclasts
How do GH and IFG-1 work together?
GH mobilizes substrate [sugar, fat, protein via lypolysis, gluconeogenesis]
IGF-1 incorporates it for growth
what is tonic inhibition? ex of AP hormone under tonic inhibition?
- most of the time we are under inhibition by default
- prolactin by dopamine
What 2 things cause increase in prolactin?
- pregnancy
- breast feeding
What is action of ghrelin?
- hunger hormone
- when food comes in it is stimulated
- it stimulates GH
What are the two hormones of thyroid? which is largest quantity? which is most active? which is used to measure thyroid function?
T4 [thyroxine]: largest quantity, used to measure thyroid function
T3 [triiodothyroxine]: most active
What is effect of T4/T3 on TSH?
inhibits TSH release from AP
What 4 things are in glycoprotein hormone family?
- TSH
- FSH
- LH
HCG
What is same vs unique in glycoprotein hormones?
- two peptide subunits
- identical alpha, unique beta chains
What does HCG do?
stimulates TSH receptor on thyroid so you get more T3/T4 but low TSH
in pregnancy
Why is glycosylation of TSH important? why can it be falsely measured as high in our blood assays?
- glycosylation of TSH is needed to convey specificity for its receptor
- improperly glycosylated TSH will not bind to receptor and have action
- clinically we can measure it and think its ok but it might not be functional –> may have normal TSH level but not internalized/functioning/etc
What is situation when you could have normal TSH but hypothyroidism?
clinically we can measure TSH levels and see its normal but it might not necessarily be functional/glycosylated
if have sick pituitary it might put out messed up TSH that doesnt work
so we have normal TSH LEVEL but not function
and very low T4/T3 [hypothyroidism]
What is action of TSH?
- thryoid cell growth and differentiation
- hromone synthesis
via cAMP
What percentage T4 vs T3?
80% T4, 20% T3
What is major circulating hormone? why?
T4 - produced in large quantity, and long 1/2 life
Where does T3 come from?
- directly from thyroid
- converted from T4 in tissue, allows tissue specificty – tissues can decide if they need it
Where in thyroid are T3/T4 made?
in thyroid colloid
What is contained in thyroid colloid?
thyroglobulin
What are the steps of T3/T4 formation?
- TG synthesis in follicular cell
- I transported into basolateral side of follicular cell via Na-I cotransport
- I enters follicular lumen and oxidized to I2 [iodine] by thyroid peroxidase
- I2 binds tyr residues on TG to form MIT and DIT by thryoid peroxidase
- MIT and DIT couple to for T3 and T4 by thryroid peroxidase
- TG endocytosed into follicular cell at stimulation from TSH
- T3 and T4 hydrolyzed in lysosomes and enter circulation by proteases
- residual MIT and DIT deiodinized and recycled by deiodinase
Where is TG [thyroglobulin] synthesized?
in follicular cell
What brings I into follicular cells?
Na I cotransport
What 2 things inhibit Na I cotransporter in thyroid?
- perchlorate
- thiocyanate
What 3 things does thyroid peroxidase do?
- oxidation I –> I2 [iodide to iodine]
- binding I2 to tyr residue of TG to make MIT / DIT
- coupling MIT and DIT to T3 [or two DIT to T4]
What does PTU [propylthiouracil] inhibit?
it inhibits thyroid peroxidase
- oxidation I –> I2 [iodide to iodine]
- binding I2 to tyr residue of TG to make MIT / DIT
- coupling MIT and DIT to T3 [or two DIT to T4]
Where is T3/T4 hydrolyzed from TG?
lysosome in follicular cell, by proteases
What happens to leftover MIT and DIT on TG?
- deiodinized in follicular cell by deiodinase
What is effect of thyroid deiodinase?
have I deficiency since you can’t recycle it
What is mechanical reason for more T4 than T3?
peroxidase rxn of combining two DIT is faster than one DIT and one MIT
What is Wolff-Chalkoff effect?
- high level of I in thryoid inhibits organification [formation MIT/DIT] and synthesis of thyroid hormones
- inhibits thyroid peroxidase
What can you use to take a thyroid scan?
radioactive iodine [in small dose]
What 2 things can radioactive iodine in large dose treat?
- treat hyperthyroidism to destroy thyroid tissue
- treat thyroid cancer in really large doses
What can large does of non-radioactive iodine treat?
- can treat hyperthyroidism
- because of Wolk-chalkoff effect, large I blocks more thyroid hormone production
What is mech for escape from wolk-chaikoff effect?
escapes after 10 days
over space of a week all that iodine actually downregulates the transporter so less I comes in so thyroid is able to recover
How does T4 normally circulate?
bound to thyroid binding globulin [TBG]
99% bound
What happens if you don’t have TBG?
lower T4 but might still be normal
Where does majority of T3 comes from?
75% from conversion from T4 in liver, heart, muscle, fat, CNS, pituitary
25% directly from thryoid
What type of deiodinase to downregulate T3?
type 3 deiodinase
What type of deiodinase to upregulate T3?
Type 1 and Type 2
Does thyroid hormone bind outside or inside cell?
inside cell
Where does T4-> T3 conversion happen [extra or intracellular]?
intracellular
What are effects of thyroid hormone
growth: growth formation, bone maturation
CNS: maturation of CNS
BMR: more Na-K atpase, more O2 consumption, more heat production, increased BMR
metabolism: more glucose absorption, more glycogenolysis, more gluconeogensis, more lypolysis, more protein synthesis and degradation [net catabolic]
CV: more CO
What happens to growth without thryoid hormone?
no growth
What happens to brain development and function without thyroid hormone?
no brain development and function
What is effect of thyroid hormone on heart
- increases BMR
- increases CO
- increases thermogenesis so radiating heat out
- can lower BP because vasodilation to radiate heat out
- increases HR
- increases contractility
Without thyroid hormone are you more likely to be hypoglycemic or hyperglycemic?
hypoglycemic
What does thyroid hormone do to cholesterol?
“helps you get rid of bad cholesterol and hold onto good cholesterol”
- increases ApoA1 [protein on HDL]
- increases good HDL levels
- increases binding of LDL to LDL receptor in liver
- increases path of LDL/cholesterol breakdown to bile acid in liver
Effects of T3 on kidney
- increases renal blood flow
- increases Na reabsorptin
- increasees RAAS
- increases GFR
