Cushings/Pituitary/Adrenal Flashcards
Single chain of 191 amino acids? What cell type of ant pituitary releases?
Growth hormone
Somatotrophs (acidophilic)
Single chain of 39 amino acids? What cell type releases?
ACTH
Corticotrope (basophilic)
Single chain of 198 amino acids? What cell type releases?
Prolactin
Lactotroph (acidophilic)
3 glycoprotein hormones released by ant pituitary and the cells producing them?
TSH (Thyrotropes)
FSH (Gonadotropes)
LH (Gonadotropes)
2 hormones produced in hypothalamus/stored in post pituitary? How do they differ in chemistry?
Oxytocin
Anti-diuretic hormone
Both are polypeptides with 9 amino acids.
Oxytocin contains isoleucine + Leucine
ADH contains phenylalanine + arginine
What are the 3 components of the anterior pituitary gland and what cell types are found in each?
Pars distalis
-All types
Pars intermedia
-Corticotrophs -> ACTH + MSH
Pars tuberalis
-Gonadotrophs + Thyrotropes -> FSH LH TSH
In what structures of neurons are hypothalamic hormones stored before release from posterior pituitary?
Herring bodies within neurosecretory granules.
How do releasing/inhibitory hormones get from the hypothalamus to the anterior pituitary?
How do anterior pituitary hormones get to the systemic circulation?
Hormones from hypothalamus are released from axon terminals at the median eminence.
They enter a primary capillary network which is derived from the superior hypophyseal artery (from int carotid)
They enter the primary capillary plexus and travel via the hypophyseal portal system to the secondary capillary plexus to reach the anterior pituitary cells.
Hormones released from the anterior pituitary exit into the system circulation via:
-Hypophyseal veins -> cavernous sinus -> petrosal sinus -> internal jugular vein.
Two functions of Anti-diuretic hormone?
Increases water reabsorption from kidneys back into blood
Regulates blood pressure/blood volume
Two physiological changes related to blood that results in ADH secretion?
Low blood pressure
- less stretch of atria stretch receptors / baroreceptors of aortic arch + carotid sinus
-Less inhibitory signals sent to medulla (and subsequently to hypothalamus) via vagus + glossopharyngeal
-increase in ADH secretion
Increased osmolarity of blood (not enough water)
-results in depolarisation of osmoreceptors in hypothalamus
-ADH release.
MOA of ADH on water reabsorption?
Collecting ducts/tubules
-Binds to its GPCR on tubular epithelial cells
-Activates Adenylyl cyclase
-Increases cAMP
-phosphorylation of aquaporin vesicles
-Insertions of aquaporins onto luminal surface of epithelial cells
Two functions of oxytocin?
Uterine contractions
-Binds to GPCR of uterine smooth muscle cells.
-Downstream cascade of intracellular signalling
-Influx of calcium
-Myosin-cross bridge formation
-Contraction
-Positive feedback for continued contractions.
Milk ejection through contraction of myoepithelial cells
From what layer of the adrenal cortex is cortisol secreted?
What hormone from the pituitary stimulates its release? What is its structure? What type of cell does this originate from? What hormone from hypothalamus stimulates this cell?
Zona fasciculata
ACTH
Single chain 39 amino acid
Corticotrope
CRH
MOA of glucocorticoids
-Travel in blood bound to steroid binding globulin- active.
-Some travels in plasma, unbound - active
-It is lipophilic and so diffuses into cell.
-Binds the intracellular receptor which is bound by a
heat shock protein
-Binding the receptor results in dissociation of HSP
-Translocates to nucleus
-Alters gene expression
- Upregulates anti-inflammatory genes (trans-activation):
(i)Anexin-1 activation
—> Activation of anexin 1 leads to inhibition of phospholipase A2-alpha.
—>This blocks release of arachidonic acid from cell membranes
—> This inhibits production of ecosanoids i.e. prostaglandins + leukotrienes.
(ii) MAPK phosphatase 1 activation
—> leads to dephosphorylation and inhibition of MAPK family of proteins
—> decreased intracellular signalling
—> inhibition of phospholipase A2-alpha
—> blocks release of arachidonic acid
- Downregulates pro-inflammatory genes (transrepression): NFkB, Activator protein 1
(i) NFkB: normally binds DNA to promote transcription of inflammatory mediators + COX-2 enzymes
(ii) Activator Protein 1: Normally acts in the transcription of inflammatory mediators.
- Increases anti-inflammatory cytokines IL-10, IL-1ra
- Also causes non-genomic changes
How does glucocorticoid use cause immunosuppression?
- Effect on T + B cells
-reduces T lymphocyte count
-reduces activation of Th2 cells
-reduces clonal expansion
-decreases cytokine release
-reduces antibody production - Reduces expression of adhesion molecules for leukocytes to adhere to.
- Decreases vascular permeability -> more difficult for leukocytes to exit into tissue.
- Reduces complement concentration in plasma
- Reduces circulating eosinophils.
How do glucocorticoids cause osteoporosis?
Can increase the RANK-L : OPG ratio therefore rate of bone resorption > bone formation (osteoclasts more active than osteoblasts).
Can also reduce calcium absorption from small intestine -> stimulates PTH secretion.
How do glucocorticoids cause hypertension?
Increased activation of alpha-1 adrenergic receptors on vascular smooth muscle -> smooth muscle contraction.
Excess glucocorticoids can also saturate the 11-Beta HSD2 enzyme in renal tubules = less conversion to cortisone -> excess GC can mimic aldosterone by binding to its mineralocorticoid receptor to trigger sodium resorption.
What is the embryological origin of the adrenal cortex and medulla?
Cortex: Mesenchymal cells (mesoderm)
Medulla: neuroectoderm( neural crest cells from ectoderm)
outline the histological and functional characteristics of
Zona Glomerulosa
- Zona Glomerulosa
- outer layer
- overlayed by capsule of the gland
- Cells organised into rounded column groups.
- Cells are smaller than other zones
- Nuclei are dark and round.
- cytoplasm is basophilic
- Capillaries run between groups
Function: production of aldosterone using aldosterone synthase in response to angiotensin II and potassium levels.
outline the histological and functional characteristics of
Zona Fasciculata
-Cells organised into cords/fascicles
-Cords separated by fenestrated, sinusoidal capillaries.
-Nuclei are light and centrally located
-cytoplasm is light, foamy/spongey due to lipid droplets within vesicles (spongiocytes)
Function:
Cortisol + Corticosterone release in response to ACTH.
outline the histological and functional characteristics of
Zona Reticularis
- Cells organised into wavy cords which are separated by sinusoidal capillaries.
-Cytoplasm is eosinophilic.
-Nucleus is large and light - Lipofuscin; produced following oxidation of intracellular lipids; gives browny tinge.
Function:
Produces Dehydroepiandosterone (DHEA)- a precursor for androgen + estrogen- in response of to ACTH
What class of hormones are produced in the adrenal cortex vs medulla? from what are they derived? How are these synthesied?
Adrenal cortex: Steroid hormones, derived from cholesterol
Synthesis:
-80% of the steroid hormones are made using LDL’s circulating within the plasma.
-The LDLs diffuse into the intersitial space and are endocytosed by adrenocorticol cell membrane receptors contained within coated pits.
- The receptors + LDL contained within vesicle which fuses with lysosome and the cholesterol is then released for use.
-The cholesterol is cleaved at the mitochondra by cholesterol desmolase to form pregenalone (rate limiting step)
Adrenal medulla: Tyrosine derived hormone
Synthesis:
-Tyrosine -> L DOPA by Tyrosine hydroxylase
- L-DOPA -> Dopamine by DOPA decarboxylase
- Dopamine-> noradrenalin by Beta-hydroxylase (within chromaffin cell vesicles)
- Noradrenalin -> Adrenalin by P-N-Methyltransferase
Outline histological and functional characteristics of Zona reticularis
Zona reticularis
- Cell cords anastomozing with eachother separated by sinusoidal capillaries
- Eosinophilic cytoplasm
- Light and large nucleus
- Lipofuscin: produced following lipid oxidation; gives browny tinge.
Function: produces Dehydroepiandosterone (DHEA) - a precursor of androgens + estrogren- in response to ACTH.
What are the 3 classes of hormones under the heading “steroid hormones” - all of which are produced in adrenal cortex?
- Mineralocorticoids
- Aldosterone
- Deoxycorticosterone
-> Zona Glomerulosa - Glucocorticoids
- Cortisol
- Corticosterone
- Cortisone
-> Zona Fasciculata - Sex hormones
- Dehydroepiandosterone
-> Zona reticularis
