physio - E4: endocrine

3 diff classes of hormones

3 diff classes of hormones

peptides, amines, steroids

peptides & amines:
- synth
- storage
- transp
- binding location

synth = nucleus (dna/rna)
storage = vesicles until stimulus comes
transp = free (they're water sol)
binding = surface of receptor

amine types

dopamine, NE/E, thyroid hormones

which amines do vs don't require a carrier in blood

carrier = thyroid hormones
no carrier = catecholamines

steroids:
- synth
- storage
- transp
- binding location

synth = cholesterol (synth & secreted on demand!!)
storage = adrenal cortex & gonads
transp = carrier protein (not water sol)
binding location = intracellular receptors -> activate/stop transcription

steroid types

cortisol, aldosterone, testosterone, estrogen, progesterone

hormone response depends on...

- rate of secretion
- rate of elimination
- binding to proteins (inactivated when bound to protein)

most hormone secretion cases are

negative feedback - hormone A will secrete hormone B, hormone B will turn off A

primary, secondary, tertiary secretions

primary = target gland
secondary = pituitary gland
tertiary = hypothalamus

T3/T4 production pathway

hypo -> TRH -> ant pituitary -> TSH -> thyroid -> T3/4

circadian vs pulsatile pattern of hormone sec

circadian = day/night pattern
pulsatile = hormones sec at diff times; be careful with blood draw times

half-life

time it takes to reduce concentration of hormone in half

metabolic clearance rate

volume of plasma cleared of the hormone per minute

3 ways hormones can be removed from plasma

1. metab or binding to tissues
2. hepatic excretion
3. renal excretion

hormone bound to protein =

it's inactive!

(binding of hormones to protein reduce its conc)

water sol hormones such as ___ & ____ are NOT protein bound and have a faster onset of action

peptides & catechol

______ is affected by number of available receptors

response

det by number of receptors (upreg vs down reg)

sensitivity

activation of the receptor results in what 2 things

1. second messangers
2. changes in gene transcription/translation (steroids)

second messanger role

activate G proteins which activate:
1. cAMP
2. DAG
3. IP3

cAMP pathway

G prot + adenylene cyclase -> cAMP -> protein kinase A (PKA)

what is cAMP broken down by?

phosphodiesterase enzyme

DAG & IP3 pathway

phospholipase C
-> DAG -> Ca2+ -> protein kinase C (PKC)

-> IP3 -> Ca2+ release

tyrosine kinase role

phosphorylation

guanylyl cyclase activates..

cGMP

guanylyl cyclase example

ANP

what breaks down guanylyl cyclase

PDE5

(phosphodiesterase type V)

arachidonic acid produces what 4 secondary messengers

1. prostaglandins
2. prostacyclins
3. thromboxanes
4. leukotrienes

(these are secondary messengers that are hormones themselves!!)

what controls secretion of pituitary hormones from the hypothalamus?

hypothalamic-pituitary Axis (HPA)

anterior pituitary secretes what 6 peptide hormones

1. growth hormone
2. TSH
3. ACTH
4. FSH
5. LH
6. prolactin

what is the only hormone NOT secreted in response to a stimulatory hypothalamic hormone

prolactin

what inhibits prolactin?

Prolactin-inhibiting factor (PIF) AKA dopamine!

review anterior pituitary slide

:)

what maintains sensitivity of anterior pit cells

pulsatile release

what does growth hormone (GH) stimulate

insulin-like growth factor (IGF-1) AKA somatomedin C

GH opposes the effects of ______

insulin

3 functions of GH

1. lipolysis
2. reduced glucose uptake in muscle
3. gluconeogenesis

when does the pulsatile secretion of GH occur

first 2 hours of sleep

↑ GH = ___ glucose

↑

hypoglycemia -> _______ -> growth hormone release

ghrelin

2 roles of IGF-1

1. promotes growth (duh)
2. can inhibit GH secretion

post pituitary secretes what 2 hormones

ADH & oxytocin

3 roles of oxytocin

1. uterine contraction & cervical dialation
2. milk ejection (suckling infant)
3. maternal behavior

T3 vs T4

T3 = triiodothyronine
T4 = thyroxine

the thyroid contains parafollicular cells surround...

colloid (in a circle)

major protein that contains T3 & T4

thyroglobulin (TG)

thyroid hormone synth steps

1. synth & transport via TG
2. I-trap = I & Na into cell
3. oxidation of I via thyroid perioxidase (I -> I2)
4. I2 + TG
5. coupling = T3 & T4 form
6. endocytosis of TG (colloid -> parafollicular)
7. release T3/4 into blood

thyroid hormones MUST be secreted into blood and bound to what 3 proteins?

1. thyroid-binding globulin
2. transthyretin
3. albumin

diff btw T3 & T4

T3 = more active
T4 = more abundant

3 thyroid hormone roles:

1. ↑ BMR
2. gluconeogenesis
3. growth/development

how does thyroid hormone increase BMR

stimulate "futile" cells -> catabolism & anabolism of trig & protein -> body heat

what does the thyroid hormone make that increases body heat

brown adipose tissue

thyroid hormone increases ________ receptors

B-adrenergic (increases metabolic activity)

neonatal screen for ______ is performed to evaluate thyroid function 2-4 days after birth

hypothyroidism

if there's too much TSH = thyroid gland will enlarge = ____ will occur as homeostasis

negative feedback is exerted by T3/T4

17 vs 21 alpha-hydroxylase

17 = prod cortisol
21 = prod cortisol & aldosterone

cortisol role

increase glucose

(released in trauma, stress, illness, fever)

what do weak androgens produce...

progesterone = synth cortisol & aldosterone

(CANNOT prod testosterone/estrogen)

adrenal medulla contains what type of cells

chromaffin cells

adrenal medulla is innervated by

preganglionic sympathetic neurons = release Ach

cortisol = stimulates ______ synth

epinephrine!!

what prod steroid hormones

cholesterol

what is the rate limiting step of cholesterol

cholesterol -> pregnenolone

majority of cortisol is bound to binding protein called

transcortin (most cortisol is inactive)

3 actions of cortisol

1. mobilizes glucose, AA, FA
2. resists inflam & immune response
3. glucocorticoid (increase glucose)

glucocorticoid occurs in 4 ways...

1. gluconeogensis
2. AA from muscle
3. reduce metb of glucose
4. reduce sensitivity to insulin

hypothalamic pituitary axis (HPA) pathway (cortisol secretion)

stress -> hypo -> CRH -> anterior pit -> ACTH -> adrenal gland -> cortisol

cortisol exerts negative feedback/inhibits what?

CRH & ACTH

when is cortisol secreted

morning!

precursor of ACTH & MSH

POMC

production of dark skin pigment

MSH

renin is secreted from ___ cells in response to low bv

juxtaglomerular

3 things that stimulate renin release

1. ↓ distension of renal afferent arteriole
2. tubuloglomerular feedback sig --> due to ↓ GFR & tubular fluid
3. renal sympathetic nerves stim --> due to baroreceptor reflex by ↓ BP

↑ K = ____ aldosterone

↑

(aldosterone wants to retain Na, excrete K)

what produces E/NE

tyrosine

NE/E are stored where

chromaffin cells

release of catecholamines is controlled via ____

preganglionic symp neurons

where is Ach secreted

nicotinic cholinergic receptors on chromaffins

catecholamine pathway is stimulated by ___ & ___

ACTH & SNS

(acth makes cortisol & cortisol makes epinephrine!)

5 receptor types of catecholamines

a1 = g proteins = ↑ Ca
a2 = suppress cAMP
B1,2,3, = increase cAMP

explain NE/E receptor affinity

E = B1 & B2
NE/E both bind to = alpha

catecholamine short-term affects

↑CO, bronchodialation, ↑glucose

what stimulates conversion of cholesterol to pregnenolone?

ACTH

how are catecholamines inactivated

E -> COMT -> metanephrine -> MAO -> VMA -> excreted

NE -> COMT -> normetanephrine -> MAO -> VMA -> excreted

where is angiotensin-converting enzyme located?

lungs

Giving an asthmatic a B2 agonist can have what other side effect?

tachycardia

blood flows from center towards periphery in islets of langerhans, why is this important?

insulin cells are antagonistic to glucacon cells & can turn them off

alpha, beta, and D cells

alpha = glucagon
Beta = insulin, proinsulin, C peptide
D = somatostatin

3 steps of proinsulin degeneration:

1. synth with A, B, & C domains
2. C domain cleaved from proinsulin = C peptide
3. A & B chains joined to form insulin

useful marker of insulin production

C peptide in urine

effects of insulin on the Liver

Liver:
1. ↑ glucose metab
2. ↑ glycogen
3. ↑ trig
4. ↑ protein synth (inhibits protein bkdwn)

effects of insulin on skeletal muscle

1. glucose uptake into muscles via GLUT4
2. ↑ glycogen

effects of insulin on adipose tissue

1. glucose uptake into adipose tissue via GLUT4
2. ↑ trig

↑ insulin = ___ K

↓

(limit K bc it'll cause <3 issues)

what receptor mediates insulin

tyrosine kinase

explain obesity & insulin

↓ insulin receptors = insulin resistant = DM :(

steps of insulin secretion

1. glucose enters B cell via GLUT2 -> ATP
2. ATP -> inhibits ATP-sensitive K channel -> depol
3. Ca2+ in
4. Ca induced/Ca released -> exocytosis of insulin

anticipation of a meal causes stimulation of B cells via

cholinergic vagal neurons

incretins
- defintion
- 2 types?

stimulate insulin secretion
- GIP & GLP-1

↓ glucose = ____ insulin

↓