Adrenal Axis Flashcards
structure of the hypothalamus
infundibulum (stalk)
anterior pituitary
posterior pituitary
structure of the pituitary gland
Pars Tuberalis
Pars Intermedia
Pars Distalis
overview of adrenal axis
Hypothalamus secretes Corticotropin releasing hormone (CRH)
CRH acts on anterior pituitary
then ant pit secretes Adrenocorticotropin hormone (ACTH) which acts on adrenal cortex
cortex secretes cortisol which functions as the negative feedback loop
CRH synthesis and release :
central stimulatory control
CRH is made in the hypothalamic paraventricular nucleus
Central stimulatory control :
- noradrenergic
- stimulates pre-proCRH gene and protein expression (196 AA)
- processed to CRH (41 AA)
- stimulates pulsatile release of CRH
CRH synthesis and release :
Inhibitory influences
physiological levels of cortisol inhibit release of CRH (and possibly inhibit pre-proCRH gene expression)
CRH background
CRH is produced by parvocellular neuroendocrine cells within the paraventricular nucleus of the hypothalamus
CRH is released at the median eminence (at the base of the brain) from their neurosecretory nerve terminals, into blood vessels in the hypothalamo-pituitary portal system
The blood vessels carry the CRH peptides to the anterior lobe of the pituitary, where it stimulates corticotropes to secrete adrenocorticotropic hormone
ACTH synthesis & release (anterior pituitary) :
POMC family
ACTH ( adrenocorticotropic hormone) : regulates adrenal cortex function
MSH (melanocyte stimulating hormone) : skin pigmentation in response to UV radiation
End (beta-endorphin) : analgesic roles in central nervous system
Enk (enkephalin) : analgesic roles in fetus
MC3,4,5 - receptors : hypothermia, hypotension, feeding behaviour, appetite
what are convertases
enzymes that cleave POMC
different convertases give rise to different products
what is the struture of the adrenal gland
like pituitary gland; has 2 embryological distinct tissues merged during development
Adrenal cortes = steroid factory
Adrenal medulla = modified sympathetic ganglia - secrete catecholamines
what is made in the adrenal cortex ?
Glucocorticoids
Mineralocorticoids
Sex Steroids
** THREE MAIN CLASSES OF STEROID HORMONES **
what is made in the adrenal medulla
catecholamines
epinepherine
anatomy of the adrenal gland
Connective Tissue Capsule
Adrenal Cortex :
- zona glomerulosa
- zona fasciculata
- zona reticularis
Adrenal medulla
where are glucocorticoids (cortisol [ACTH]) made
zona fasciculata
how is the glucocorticoid cortisol made
cholesterol is converted into pregnenolone (via enzymes of the inner mitochondria)
becomes 17-OH pregnenolone
becomes 17-OH progesterone
becomes 11-deoxycortisol
(via enzymes of the inner mitochondria) gives cortisol
how is corticosterone (dominant glucocorticoid in rodents) made
cholesterol
pregnenolone
progesterone
deoxycorticosterone
corticosterone
why is cortisol essential for life ?
Protects against hypoglycemia (low blood sugar)
Promotes gluconeogenesis (increase blood sugar)
Plays a role in immune system, bone, muscle
cortisol and inflammation
cortisol as a natural regulator of the inflammatory response
> clinical use of glucocorticoids as anti-inflammatory agents
negative effects of cortisol
causes breakdown of skeletal muscle (for gluconeogenesis)
suppresses immune system
catabolic on bone
affects brain function (mood, memory, learning)
Cushing’s syndrome (primary)
High levels of corticosteroids in the blood cause Cushing’s Primary
- prolonged exposure to high levels of cortisol. This can be caused by taking glucocorticoid drugs, or diseases that result in excess cortisol, ACTH or CRH levels
Cushing’s disease (secondary)
A pituitary-dependent cause of Cushing’s syndrome: a tumor in the pituitary gland produces large amounts of ACTH, causing adrenals to make excess cortisol
How do you distinguish Cushing’s syndrome (primary hypercortisolism) from Cushing’s disease (secondary hypercortisolism)
ACTH levels are lower in the syndrome form
Effects of Cushing’s syndrome
causes changes in carbohydrate & protein metabolism, hypergycemia, hypertension, muscular weakness
Metabolic problems give rise to puffy appearance, CNS disorders (depression, decreased learning, memory, etc.)
Treatment of Cushing’s syndrome
- surgery to remove pituitary or adrenal gland (depending on which is causing it)
- medical management of signs and symptoms (eg/ insulin for diabetes, anti-hypertensives for BP)
if not treated, disease worsens, overall health can deteriorate, especially worsening diabetes, high BP - that can lead to strokes or MI
What is Addison’s disease ?
primary hypocortisolism
Adrenal insuffiency, many causes including genetic, autoimmune destruction of adrenal cortex
when acquired; high dose steroids >1 week begins to suppress adrenal glands by suppressing CRH and ACTH
Adrenal cortisol secretion
continuous, pulsatile, circadian rhythm
ie/ goes down when you go to bed and increases in the day
what happens with insomnia
people with insomnia secrete more cortisol around sleep time
PPID in horses
pituitary pars intermedia dysfunction
affects : older horses but has been diagnosed in horses and ponies as young as 10
cause (impaired pituitary gland) :
hyperplasia & hypertrophy of the pars intermedia of the pituitary gland
increased secretion of cortisol by adrenal glands
results in high blood glucose and suppression of the immune system
what are the common signs of PPID in horses
- Hypertrichosis (excessive hair growth)
- Abnormal hair coat including patches of long hair on the legs, wavy hair on the neck, changes in coat colous
- muscle atrophy
- excessive sweating
- formation of fat pads on top of the neck, tail and above and around the eyes
- pot-bellied appearance
how do you diagnose and treat PPID in horses ?
Diagnosis : measuring basal ACTH & fasting insulin
Treatment :
Drug - Pergolide; acts on the pituitary gland to decrease circulatinh ACTH
Management - exercise, weight loss (if obese), limit starch/sugar in horse’s diet
