Endocrine Day 2- GH/Female reproductive Flashcards
What is the pathway for short loop negative feedback for GH?
- GH released from ant pituitary somatotrophs after stimulation by GHRH
- GH “feedbacks” to arcuate nucleus and ventromediolateral hypothalamus to decrease further output of GHRH and increase somatostatin release
- Somatostatin release from periventricular nucleus, reached somatotrophs and inhibits their release of GH
What does GHRH do at cellular level of somatotrophs?
Causes increase in cAMP which leads to GH synthesis
GHRH and somatostatin are released in _____ fashion from hypothalamus
alternating
What are the 3 main feedback functions for regulation of GH?
- Long-loop negative feedback
- Insulin-like growth factor is released from liver
- this feeds back to pituitary and hypothalamus to inhibit further GHRH release from hypothalamus and GH from pituitary
- also feeds back to increase somatostatin release from hypothalamus
- Short-loop negative feedback
- GH feedsback from pituitary to hypothalamus, inhibiting further GHRH release and increasing somatostatin release
- Ultra short loop negative feedback
- GHRH neuron feedbacks on itself at hypothalamus to decrease further output GHRH
- Also ultra short loop for somatostatin to decrease its further output
GH release is very ____ because of multiple layers of feedback
defined
The ___ ___ ___ is responsible for the pulsatile pattern of GH.
Ultra short loop
___ ___ is rapid acting, robust feedback of GH
short loop
____ is longer term, regulator of output of GH
IGF-1
What molecule is GH similar to in structure?
What can this be used for?
Prolactin
- When GH present in excessive amounts, can bind to prolactin receptors and cause increase in milk production in cattle
What are some effects of GH at adipose tissue?
Decrease glucose uptake
Increase lipolysis
Overall, decrease adiposity
What does GH do at liver?
- Increase RNA synthesis
- Increase protein syntheiss
- Increase gluconeogenesis
- Increase somatomedin C
What does GH do at muscle?
- Decrease glucose uptake
- Increase amino acid uptake
- increase protein synthesis
Overall, increase lean body mass
Remember, this is only in RESTING muscle cells
GH is a _____ hormone and ____ glucose concentrations
hyperglycemic; increases
Inhibits glucose uptake by adipotcytes and resting muscle cells
What is effect of somatomedin C and GH at bone, heart and lung?
- Incrase protein synthesis
- Increase RNA synthesis
- Increase DNA synthesis
- Increase cell size and number
Overall, increase organ size and increase organ function
What are some effects of GH and somatomedin C at chondrocytes?
- Increase AA uptake
- Increase protein synthesis
- Increase RNA synthesis
- Increase DNA synthesis
- Increase collagen
- increase chondrotin sulfate
- increase cell size and number
Overall, incrases linear growth
GH targets liver to produce IGF-1, this goes on to ____ ___ and ___ ___ release
Inhibit GHRH/GH ; Increase SS
Why was IGF-1 originally called somatomedin C?
Because it regulates effects of GH by increasing SS
Both IGF and GH work ____ and ____ on bone, heart, lung and chondrocytes
together and independently
What is a potential side effect of taking growth hormone (abusing GH)?
Can cause tumor growth.
Normally, immune system takes care of tumors, BUT with extra GH, tumors can proliferate in size and metastasize
What is IGFs role at bone, heart, lung, chondrocytes?
Stimulatory, like GH up until a point, then plays a role in inhibition
“stimulation then inhibition”
From med notes:
- A point of clarification on somatomedin C (IGF-1): it is often not the IGF-1 secreted by the liver that is mediating the effects of growth hormone, but rather, the IGF-1 production and secretion by the local tissues.
- In most cases, the growth hormone will travel to the target tissues, whether that is muscle, adipose, etc. and cause a local increase in the release of IGF-1, which then mediates the effects of growth hormones on tissues nearby.
- The two hormones work together – it is a combination of the direct effects of growth hormone and those effects mediated locally by IGF-1.
Growth hormone is thought of as a ____ hormone
anabolic
Increasing muscle mass while decreasing fat
What stimulates GH/GHRH release?
- Glucose decrease- triggers stimulation of GH so it can exert its hyperglycemic/lipolytic effect and increase BG in body
- FFA decrease
- AA increase- stimulate GH to uptake excess AA to enlarge/proliferate cells
- fasting (same as glucose/ffa decrease)- same as glucose/ffa decrease
- prolonges caloric deprivation
- stage 4 sleep- largest release of GH during 24 hour period
- exercise-
- stress-physiologic (Exercise) and psychological stress will trigger output of GH to increase BG available in blood stream
- estrogen/testosterone
- dopamine
- serotonin
- alpha adrenergic agonist
- GABA
- Enkephalin
bold= talked about in class
What inhibits GHRH/GH release?
- Glucose increase
- FFA increase
- cortisol
- low cortisol- increases GH synthesis
- high cortisol levels- (ie chornic stress)- inhibits GH
- ie child in abusvie
- obesity- inhibit GH secretion byincrease in FFA/glucose
- pregnancy-
- HCG is like GH- when placenta grows and makes HCG, gives negative feedback to decrease amount of GH
- somatostatin
- GH
What is the GH plasma concentration like in males?
- Male have more testosterone than females
- Testosterone highly anabolic and increase GHRH and somatostatin
- Causes high peaks of GH and very low troughs (caused by SS)
- Very regular, every 4 hours
What is the GH plasma concentraiton like in females?
- Somewhat elevated baseline
- more peaks of release and can be more erratic
- peaks of GH are not as high
Still overall positive effect on GH
- Estrogen causes less production GH compared to testosterone
Why are females, in general, shorter in stature than males?
- Males have more regular pattern, have larger growth in stature.
- Females will be taller at start of puberty
- due to fact that females enter puberty earlier
- making lots of estrogen before males making testosterone
- estrogen at epiphyseal plates- estrogen secreed and process growth sooner, but causes earlier closure of plates and cessagtion of growth
- In males, testosterone close the end plates, but males will have maximal hormone secretion and GH production
What is the difference in response of GH to acute stress and chronic stress?
- In acute stress, cortisol is elevated and leads to increase in protein syntheiss, including GHRH, leading to increase GH synthesis
- In chronic stress, long term elevation cortisol is catabolic
- this decreases protein synthesis and drops level of GHRH and therefore GH
When is the highest amount of GH released in a 24 hours period?
Deep sleep
What is prenatal growth dependent on?
- Non GH dependent
- GH does not stimulate fetal growth since it is not produced in adequate levels to yield enough IGF-1
- Is IGF-2 dependent
- IGF2 can stimulate growth without interaction of GH
What is output of GH in childhood?
- At birth, growth process switches to be mediated by GH and IGF-1
- During childhood, relative increase in GH and plateaus until puberty
What happens to GH production during puberty?
- Huge increase in sex hormones causes increase in GH
What is the adult level of GH?
- Rate of sex steroid produciton slows after puberty causing plateau to adult level
- Total GH output slows
What does GH production look like in senescence?
- Sex steroid levels decline with age, GH declines
- Leads to loss of muscle mass, increase fat deposits
- Research to counteract effects by pulsatile releases of GH as opposed to pill (which would cause more side effects due to constant level of GH)
What is acromegaly?
- Increased growth of soft tissues of face, increasing in tissue in hands d/t excess GH (can see enlargement of lip, jutting of jaw (prognathism), increased circumference of fingers)
- after puberty/closure of epiphyseal plates
What is gigantism or giantism?
- GH secreting pituitary tumor present at onset of puberty and continuing into adulthood
- epiphyseal plates have not yet closed and GH causes increase bone growth at accelerated rate
- If this condition is not corrected in childhood, can develop acromegaly once plates close