Anterior Pituitary Flashcards
What types of receptors are used by anterior pituitary hormones?
tyrosine kinase (STAT): GH, PRL
GPCR (cAMP): ACTH, LH, FSH, TSH
GH has ___ forms. What is the difference?
2
major form: 22kDa, shorter form 20kDA (less activity)
GH made from _____ is used to treat ____.
recombinant technology
pituitary dwarfism
What hypothalmic hormones control GH release?
GHIH/somatocrinin
GHRH/somatotropin
What is the effect of GH on the liver?
cause release of somatomedins (Insulin-like growth factors) -> cell division, protein synth, bone growth
What are metabolic effects of GH?
more fat breakdown
less glucose uptake by muscles (blood glucose rises)
GH has the opposite metabolic effects of _____
insulin
GH promotes growth/energy use, inhibit storage
What trigger the hypothalamus to stimulate Gh release?
deep sleep, exercise, stress, low blood glucose, high AA, low FA
What are the direct and indirect actions of GH?
Direct: mobilize energy and promote cell differentiation
Indirect: induce IGF-1 -> insulin-like effects + cell division
What does IGF stand for? What is another name for them, and what is their structure/function similar to?
insulin-like growth factors
somatomedins
similar to insulin
What are the IGF types?
IGF-1: GH dependent (made by liver/other tissues; act as endocrine, paracrine, or autocrine)
IGF-2: GH independent (fetal development)
True/false: IGF levels remain fairly constant
True (despite fluctuations in GH)
Does IGF have a carrier protein?
Yes, IGF binding protein
binds and modulates half life & activity
IGF-1 is most important during ______, but less important during _____, and is influenced by ____status
childhood growth
gestation/neonate
nutritional status
Describe the pattern of GH release in a growing child
pulsatile; pulses rise with age, maximum at puberty, then declines
What is the effect of GH and IGF-1 on bones in childhood?
promote growth at epiphyseal plates (chondrocyte proliferation)
What happens to bones at the end of puberty?
epiphyseal plates fuse (no more longitudinal growth)
___ stimulates chondroyte synthesis and increases their response to ____, stimulating _____
GH
IGF-1
cell division
____ produced by the ____ has negative feedback on GH
IGF-1
liver
The layer of bone cells (osteoblasts and osteoclasts) below the epiphyseal plate is known as the ____
diaphysis
The GH receptor is located in what tissues? What pathway is activated?
most tissues
Recruited TK -> STATs, MAPK, IP3-K
True/False: the GH ectodomain can break off into circulation
True (act as binding protein)
GHR is downregulated by ___ and ___
GH (bound -> endocytosed)
sex hormones
The IGF-1 receptor is of what type?
intrinsic TK
What is notable about IGF-2 signalling?
receptor doesn’t really do anything..
*but it can maybe bind to IGF-1 receptor but with 10% less affinity
the IGF-2 receptor can also bind ____
mannose-6-P
Pattern of GH release during sleep:
pulses: secretion every 1-2 hours
low blood ____ or the amino acid ____ will trigger increase in GH
glucose (hypoglycemia)
arginine
Glucose and fatty acids will increase ____ release from the hypothalamus
somatostatin (to stop GH)
The effects of IGF-1 are antagonized by ____
cortisol
What is a simple test for GH response? (2)
- glucose spike: GH should decrease in response
2. insulin injection (induced hypoglycemia): GH should rise
What hormones increase or decrease GH?
decrease: glucocorticoid
increase: estrogen
Hypothyroid children have (increased/decreased) growth. Why?
decreased (stunted)
thyroxin (T4) promotes GH gene transcription
Why does estrogen increase GH?
sensitizes somatotrophs to produce GH
The 2 major growth spurts in life:
Which one relies on GH?
postnatal growth spurt
pubertal growth spurt (GH very important)
GH (increases/decreases) with age. What is this called?
decreases
somatopause
Is GH therapy beneficial for elderly?
Overall no.
It can decrease fat, increase lean muscle, bone density, cog. function
BUT: side effects - edema, joint pain, breast dev., metabolic imbalance, cancer risk
Main function of PRL:
postpartum activation of lactation
Describe the hormones/development of the mammary gland:
estrogen, GH, cortisol -> growth of duct system
estrogen, GH, cortisol, PRL -> alveolar growth
(also involve insulin, thyroid hormone)
What 2 hormones are essential to initiate/maintain milk secretion?
PRL, cortisol
What happens to milk production if the pituitary is removed?
milk production immediately stops
What happens to milk production if the adrenals are removed?
gradual reduction in milk production
What hormones must decrease for milk production? What causes the decrease?
estrogen and progesterone (high levels suppress milk)
levels drop with loss of placenta
PRL stimulates the milk _____ from _____ cells into the ______.
Oxytocin induces _____ in the _____, forcing the milk out through the ____.
production; alveolar epithelial cells; lumen
contraction; alveoli; duct
What other functions (aside from milk) does PRL have?
regulate reproductive system
immunomodulation
act synergistically with other hormones
True/False: PRL receptors are found on most tissues
True (act together with other hormones)
How does high levels of PRL influence the reproductive system? (2)
too high -> hypogonadism
Lactational amenorrhea (natural birth control)
How does PRL affect immune cells?
receptors on T cells, B cells, macrophages
act as mitogen -> promote survival
The PRL receptor is similar to the ____ receptor. What type is it?
GH
recruited TK -> MAPK, STATs, IP3-K
what is the PRL releasing hormone?
Doesn’t exist
Only negative control (dopamine)
(TRH and VIP can promote release through antagonizing dopamine)
ACTH stands for:
adrenocorticotrophin
What is the precursor for ACTH? What else does it yield?
pro-opiomelanocortin (POMC)
Cleaved -> gamma-MSH, ACTH, Beta-lipotropin
Where does MSH come from?
alpha MSH: from amino-terminal fragment of POMC
beta MSH: from cleaved ACTH
gamma MSH: from cleaved beta -> gamma lipotropin
What gives rise to endorphins? (precursors)
POMC -> beta lipotropin -> beta endorphins
What effect does endorphins have?
morphine-like activity (high)
What role does MSH play?
darkening of skin
What role does ACTH play?
adrenal steroidogenesis
What is the purpose of MSH? Where does this occur?
produced by Keratinocyte (skin) -> stimulate melanocyte to make melanin
keratinocyte uses melanin to protect from UV damage
Action of ACTH:
bind receptors in adrenals -> increased cholesterol mobilization/conversion to pregnenolone
What type of receptor is the ACTH receptor?
GPCR (Gsa) - cAMP
ACTH secretion is controlled by: ______ which is affected by factors such as (4)
CRH from hypothalamus
stress (pain/fear/fever/hypoglycemia)
dark/light cycle
other hormones (vasopressin)
feedback control from cortisol
At what time of day does ACTH peak? When is it lowest?
morning peak, lowest at midnight
What is TSH?
thyrotropin (thyroid stimulating hormone)
What is the structure of TSH?
2 protein chains (a and b), glycosylated
The TSH receptor is of what type?
GPCR-cAMP
What does TSH do?
stimulate metabolism of thyroid follicular cells (forming thyroid hormones)
What is the major control system for TSH release?
feedback control
What are the gonadotropins?
LH
FSH
compare the structure of the gonadotropins with TSH:
same a subunit, but different b subunits (overall same basic structure)
Actions of LH: (4)
female: steroidogenesis in ovarian follicle, induce ovulation , maintain steroidogenesis in CL
male: stimulate testosterone production in Leydig cells (testes)
Actions of FSH: (5)
female: stimulate dev. of ovarian follicle, estradiol production
male: spermaogenesis, producing sex-hormone binding globulin
both: inhibin secretion (neg feedback)
____ is stimulated by FSH, which has negative feedback effects
inhibin
What is the pattern of gonadotropin release?
pulsatile (every 60 min in response to GnRH)
Where is inhibin produced?
Sertoli cells (testes) Ovary
How can LH stimulate the sertoli cells indirectly?
stimulate testosterone production from leydig cells -> testosterone stimulates sertoli cells
Most anterior pituitary disorders are due to:
benign tumors (adenomas)
What is an adenoma?
benign tumor, arises from adenohypophyseal cells, slow growing
microadenomas <10mm
macroadenomas >10mm
What is a non-functioning adenoma? In what age group is this more common?
does not cause excessive hormone production, usually cause function loss due to pressure/increasing size
more common in older people
What is the least common pituitary adenoma type
TSH cell adenoma (1%)
What is the most common cell-specific adenoma types?
PRL cell adenoma (30%)
GH cell adenoma (15%)
ACTH cell adenoma (10%)
Gonadotroph adenoma (10%)
What are the possible impacts of tumours on pituitary function? (4)
hypofunction hyperfunction mass effect (pushes on gland) impinges on optic chiasm -> visual field defects (diplopia, ptosis, altered facial sensation)
A swelling pituitary tumor can push on the ___ ____, causing visual field defects such as ___, ___, or _____
optic chiasm
diplopia (double vision)
ptosis (droopy eyelids)
altered facial sensation
hypopituitarism can be caused by: (4)
adenomas, surgery, radiation, trauma
What is the sequence of function loss of the pituitary, due to mass effect (swelling)
GH
Gn
ACTH
TSH
GH deficiency leads to (3):
decreased muscle strength/exercise tolerance
lower libido
more body fat
Gn deficiency lead to: (5)
oligo/amenorrhea lower libido infertility hot flashes impotence
ACTH deficiency leads to: (4)
malaise
fatigue
anorexia
hypoglycemia
TSH deficiency leads to: (5)
The symptoms are clinically similar to ______
malaise leg cramps fatigue dry skin cold intolerance
similar to primary hypothyroidism
Why might tumours arise in the pituitary? (2)
de novo (mutation) lack of feedback control
what causes Cushing’s disease?
defect in negative feedback control of CRH and ACTH by cortisol
body keeps releasing CRH to stimulate ACTH-producing cells -> forms tumour
tumours affecting the _____ and ____ hormones are rare
gonadotropins (FSH, LH)
TSH
What is the most common cure for hyperpituitarism?
surgery through nose -> remove part of gland
excess of PRL is known as _____, and causes: (6).
prolactinoma
oligo/amenorrhea galactorrhea infertility decreased libido headache visual field defects
Effect of GH excess: (2)
gigantism/acromegaly
elevated IGFs
What is the treatment (2) for GH excess?
long-acting somatostatin analogues
surgical removal (best option)
symptoms of acromegaly:
high GH visual field defects large nose/jaw, separated teeth abnormal glucose tolerance test (glucosuria) sweat gland hypertrophy sexual dysfunction
What would be the results of a glucose tolerance test in a patient with acromegaly
no decrease in GH (remains high constantly)
What is the treatment for dwarfism?
GH therapy (hypertropin) -> allows growth to catch up to normal range
What is Cushing’s disease?
excess ACTH -> excess cortisol production
Symptoms of cushing’s disease:
upper body obesity buffalo hump red round face high BP, blood sugar acne cognitive difficulties
What does excess TSH cause? (symptoms)
What is it clinically similar to?
heat intolerance weight loss weakness tremor sinus tachycardia heart failure
similar to hyperthyroidism
How is diagnosis done for pituitary disorders? (2)
MRI
specific tests to see if hypo or hyperfunctional
How is GH deficiency diagnosed? (3)
insulin tolerance test
GH-RH arginine test
IGF-1 levels
How is gonadotropin deficiency diagnosed? (3)
sexual history
menstrual history
FSH/LH/estradiol/PRL/testosterone levels
How is ACTH deficiency diagnosed? (3)
Morning cortisol levels
cosyntropin test
insulin tolerance test
How is TSH deficiency diagnosed? (2)
T4 levels
TSH levels
the insulin tolerance test is used for diagnosing what pituitary hormone deficiencies?
GH
ACTH
How is PRL excess diagnosed?
PRL level
drug history
clinical setting
How is acromegaly diagnosed?
IGF-1 level, oral glucose tolerance test
How is Cushing’s disease diagnosed?
24 hr urine cortisol
overnight dexamethasone suppresion test
How is TSH excess diagnosed? (2)
free T4, T3 levels
TSH levels
What is the usual treatment for prolactinoma?
dopamine agonist therapy to suppress
bromocriptine -> bind/activate dopamine receptors
Somatostatin analogues are used to treat : _____ (2)
acromegaly
TSH producing adenomas
