Endocrinology Flashcards
Physiological response to hormones depends on (2)
- [hormone] free, biologically active active
2. sensitivity of target cell
Hypo secretion
too little hormone activity
increased clearance
tissue resistance
hyper secretion
too much hormone activity
reduced plasma protein binding
reduced clearance
excessive response at target tissue
Role of the hypothalamus
regulates and coordinates responses to changes in the external and internal environment–
1. regulates behaviour (reproduction, feeding, rage)
2. vegetative role- maintains homeostasis
(body temp, metabolism, growth, stress, reproduction)
What is the hypothalamus made up of?
Neural tissue and endocrine gland
Small (releasing hormones)and large bodied (AVP and OT to PP) neurons.
What does the hypothalamus secrete
neurohormones
Anterior pituitary gland is made up of
endocrine cells that secrete hormones into the general circulation
What hormones are released by the AP
- TSH
- ACTH
- GH
- LH and FSH
- prolactin
What cell type of the AP produces GH
somatotrophs
What cell type of the AP produces prolactin
Lactotrophs
What cell type of the AP produces LH and FSH
Gonadotrophs
What cell type of the AP produces TSH
Thyrotrophs
What cell type of the AP produces ACTH
Corticotrophs
what are Trophic hormones and which ones are they
control activity of another endocrine gland
- ACTH
- TSH
- LH
- FSH
Non-trophic hormones
Hormones which have a direct effect
-prolactin and GH
How is the secretion of AP hormones controlled
secretion is in response to neurohormones/ releasing hormones/ releasing factors from the hypothalamus into the portal system of the AP.
what do releasing factors do? how to they function
they act on target cells to stimulate synthesis and secretion of AP hormones.
circulated in portal circulation
where are releasing hormones secreted from
nerve endings into capillaries at the median eminence
What happens to hormone secretion if the hypothalamus is disconnected from the AP
All hormones but prolactin are down regulated- they are no longer stimulated by RF. Prolactin has a Release inhibiting Factor.
what is the Releasing inhibiting factor of prolactin
dopamine
what is the Releasing inhibiting factor of GH
somatostatin
GH RF
GHRF
Structure of hGH
191 amino acid single chain polypeptide folded into a globular protein
When are the [GH] highest in the blood
during sleep
GH is pulsatile- shows rhythm. what is the difference between males and females
Females- small amplitude, frequent more continuous
males- large amplitude, infrequent, more pulsatile
How does GH secretion change over a lifetime
high in neonate
decrease in childhood
rise again at puberty
fall during childhood.
What type of receptor is the somatostatin receptor
GPCR
How is GH regulated
through a negative feedback system
what are the actions of GH
- Acts to redistribute nutrients towards production processes such as growth.
- major determinant of growth
- increase in number and size of cells in soft tissues
- increase thickness and length of long bones
+ metabolic actions
Actions through direct effects and the production of IDF1
IGF1????
- produced by liver and other tissues in response to GH
What are the iGF-1 signaling pathways
Pi3Kinase/ AKT
MAPkinase
Why are plasma IGF1 levels so stable from
hour to hour when its secretion is
stimulated by a pulsatile pattern of GH
Synthesis of IGF1 takes time following GH + IGF binding proteins maintain pool= slower degradation
Bone growth occurs at
the epiphysis.
GH causes —in bones
while IGF1 causes—
- proliferation
2. hypertrophy
what causes growth plates to close
oestrogen action after puberty
Gh/IGFH no longer cause growth- but can increase thickness
Direct GH actions in
- muscle
- AT
- Liver
- stim AA uptake, decrease glucose uptake, inhibits protein breakdown
- decreases glucose uptake, increases fat breakdown
- increase protein synthesis, increase gluconeogenesis
(increase BG)
GH hyposecretion
in adults
in children
adults: no major symptoms
children: pituitary dwarfism
GH hypersecetion
adults
children
children: gigantism
adults: acromegaly (large extremities,
Prolactin structure
Polypeptide (199 AA)
What inhibits prolactin secretion
dopamine
What Stimulates prolactin release
TRH, VIP, AVP or?
Dopamine effect on prolactin
inhibits prolactin
- secretion- short term response
- synthesis- medium term response
- Lactotroph proliferation- long term response.
How does dopamine act to prevent prolactin secretion from lactotrophs
?
What are the actions of prolactin
- stimulates alveolar epithelium cell of mammary gland to synthesise and secrete milk
- many other non-reproductive roles eg. immune system, behaviour
What signaling pathway does GH use
- JAK/STAT pathway –> gene expression
- JAK/MAPK–. gene expression
- P13K/AKT- cytoplasm
What is the somatomedin hypothesis ?
GH acts to produce another hormone (IGF1) to cause growth.
Prolactin signalling pathways
JAK/STAT
Janus Kinase Signal transducer and activator of transcription
How does a negative feedback loop function with prolactin
maintains low prolactin in non-lactating individuals. Causes dopamine release. Inhibits PRL synthesis and secretion from lactotrophs
Regulation of prolactin in lactation
Lactation inhibits dopaminergic neurons in hypothalamus
What receptors are sensitive to a baby suckling
Machanoreceptors –> hypothalamus
Too much prolactin (hyper-secretion)
form pituitary tumours “prolactinomas”
What are the two main neurohormones produces from the posterior pituitary gland
Vasopressin and oxytocin
both are peptides with 9 AA residues
Where are vasopressin and oxytocin expressed
in both the SON and PVN
Actions of Vasopressin
Decrease water excretion kidneys ‘anti- diuretic’
vasoconstriction
secretion of vasopressin is regulated by
[solute] in ECF
blood volume
Actions of oxytocin
parturition: stimulates contraction of uterine smooth muscle
lactation: milk ejection during breastfeeding due to contraction of SM
Secretion of oxytocin is stimulated by
Pressure of baby in birth canal
sucking baby
secretion is inhibited by fear, anxiety
What are the oxytocin target cells
Secretary alveolus of breast
