Growth Hormone & Somatomedin Flashcards
Somatotrophs comprise ~ _% of the hormone-producing cells of the anterior pituitary
50%
Secretes growth hormone
Major physiological effects of GH
Stimulation of postnatal somatic growth & development
Modulation of metabolism in adults
Regulation of GH pulsatile secretion
- Hypothalamic hormones:
-
Growth hormone-releasing hormone (GHRH)
- Stimulates adenylyl cyclase and increases intracellular cAMP & Ca2+
- Somatostatin / Somatotropin release-inhibiting factor (SRIF) inhibits
-
Growth hormone-releasing hormone (GHRH)
-
IGF-1 / Somatomedin C
- inhibits GHRH
- stimulates somatostatin
Growth hormone therapy
higher mortality rate and higher risk of tumors
The phospholipase C/ DAG/ IP3 and PKC pathways regulat eGH secretion how?
Increasing Ca2+
Activating PKC
What hormones upregulate GH?
-
Stress, sleep, aa-rich meal –> hypothalamic GHRH release
- Short-term:
- Increases cAMP, Ca2+, and IP3
- Increases somatotroph’s GH release
- Long-term: increase GH transcription via Pit-1
- Short-term:
- Thyroid hormone & cortisol synergistically enhance transcription
- Estrogen & testosterone mildly increase GH transription & synthesis in young adults
Downregulation of GH synthesis & transcription
-
GH & somatomedin induces somatostatin –> inhibit GH release
- Somatostatin binds its own receptor to inhibit GH secretion by decreasing cAMP and Ca2+
Describe the biological action of GH
- Anabolic & diabetogenic.
- Mediated directly AND indirectly through GH-stimulated production of IGF-1 by the liver and local nonliverproduction
- IGF-1 –> linear growth, organ size, lean body mass
What impact does fasting have on GH & IGF-1?
Increase in GH (anabolic) will promote lipolysis because we now want to conserve glucose for essential tissue (e.g. brain) –> burn fat
Decrase glucose uptake by the muscle
Increase gluconeogenesis by liver
When do GH level peak in fetal serum?
Do premature of full-term infants have higher serum GH?
When does GH peak in the lifetime?
20th wk of gestation
Premature infants have higher GH
Amt of GH secreted is greatest during adolescence, then decreases with age
Somatostatin
aka
GH-inhibiting hormone
Hypothalamic peptide that diminishes the frq and amplitude of GHRH pulses
Does this by acting through its own membrane receptor –> decrease intracellular Ca2+ and cAMP
GH release pattern is also influenced by
What stimulates somatostatin (GHIH)?
Hyperglycemia
High FA
How does [glucose] and [FA} impact GH?
A sharp drop in [glucose] or [FA}, such as in short-term fasting
–> increase plasma GH
Elevation of glucose or FFA, such as in obesity
–> reduces plasma GH
How do deep vs light sleep impact GH?
How do various stresses (trauma, surgery, fever) impact GH?
Deeper sleep –> more GH
Stress increases plasma GH
What do children who have GH deficiency look like?
What does GH replacement therapy cause?
Short & moderately obese
GH therapy
- enhances positive nitrogen balance
- decreases urea production
- redistributes fats
- reduces carbohydrate utilization
Unlike other hormones, GH for humans must come from
other primates
(e.g. cant use pig like insulin
mechanism of GH at the receptor
- GH binds to JAK-STAT receptor dimer
- Intracellular domains dock and activate the JAK-STAT tyrosine kinase pathway
- Activated JAK tyrosine kinases phposphorylate STAT transcription factors –> activates GH-dependent gene transcription and expression
Somatomedins / IGFs
where do they originate? what are they produced in response to?
What happens if you have high GH but not IGF?
Produced in response to GH and are produced by many tissues, but mostly in the liver.
They mediate the typical GH responses, so not having IGFs –> retarded growth despite high GH
How are IGF’s availability to tissues regulate?
They circulate bound to large binding proteins
Both IGFs, but especially __, are greatly reduced in the plasma of GH-deficient subjects
IGF-1 is greatly reduecd in the plasma of GH-deficient subjects
Describe IGF & GH levels in the fasting condition
High GH, low IGF
Because fasting -> low insulin, high GH -> IGFs activated neg feedbacks on itself to low IGF (but GH stays high in response to low IGF) ?
Locally-produced IGF-1 contributes to the stimulatory effects of GH, especially ____
enhancement of longitudinal growth
GH & IGF in longitudinal growth of bones
GH –> stimulate differentiation of prechondrocytes into early chondrocytes, which secrete IGF-1
IGF –> stimulate clonal expansion and chondrocyte maturation
Administration of IGFs to GH-deficient children or adults decreases has what impact on:
- plasma amino acid levels
- lean body mass
- fat mass
- bone formation
- resting metabolic rate, exercise capacity, well-being
amino acid lvls decrease bc *protein synthesis*
lean body mass INcrease & fat mass DEcreases
Bone formation is enhanced
Metabolic rate, exercise capacity, and wellbeing INcrease
The most specific effect of GH is
Acceleration of linear cartilage growth center growth in long bones
Cartilage-forming cells stimulated during collagen & proteoglycan chondroitin synthesis, which forms the ECM of cartilage
Most specific tissues share in the anabolic response to GH
GH stimulates DNA, RNA, and protein synthesis in almost all cell types.
GH & senescence
Decrease in GH with aging –> less anabolic effects
In what ways does GH oppose the actions of insulin?
- GH stimulates insulin gene expression, BUT it also induces insulin resistance
- Inhibits glucose uptake by muscle & adipose cells –> increase plasma glucose
- Enhances lipolysis & opposes insulin’s lipogenesis
GH is a ___genic hormone
diabetogenic
GH has what impact on plasma free FA and ketoacids? What about on adipose tissue?
Increases plasma fFA & ketoacids
Decreases adipose tissue
Acromegaly
Excessive GH secretion after puberty
- Causes: pituitary tumor, hyperpituitarism, somatotroph tumors
- Characteristics:
- Thick & oily skin, esp face and scalp
- Delayed diagnosis: often not diagnosed until 15-20yrs old
Both GH & insulin together augment ____, leading to increased lean body mass.
What is the purpose of insulin-antagonistic effect of GH?
What happens to insulin, GH, and IGF during fasting?
Together, they augment IGF production
The insulin-anatagonistic effect of GH prevents hypoglycemia when you’re fasting (dont want high insulin)
Fasting: GH rises -> inuslin falls -> IGF declines
Prolactin’s structure is homologous to ___ and is synthesized as a ___.
What happens to it in the ER? In the Golgi?
Homologous to GH
Synthesized as a preprohormone
Temporarily N-glycosylated in the ER
Deglycosylated in the Golgi
What form of prolactin is the major circulating form in NONpregnant women?
Glycosylated prolactin is constituvely secreted because it exhibits lower biological activity
Prolactin secretion is regulated by
- Inhibited:
- Dopamine
- Somatostatin
- <strong>GnRH (alternative form)</strong>
- Stimulated: TRH
Biological effects of prolactin
- Breat development
- Milk production
- Reproductive function in both genders
Disruption of pituitary connections to hypothalamus can have what impact on prolactin secretion?
Increase prolactin secretion
Why does excess prolactin cause infertility in women and men?
Excess prolactin inhibits GnRH release –> lack of ovulation, decreased sperm production
__ contributes to stimulation of parental protective behavior in newborns
prolactin
