Physiology 3120 Lecture Notes - Lecture 6: Gluconeogenesis, Birth Weight, Corepressor
9 May 2018
School
Department
Course
Professor
Physiology 3120
Dr. Hardy
Adrenal Hormones
Functional Anatomy
- Cortex
o zones
▪ zona glomerulosa - aldosterone
▪ zona fasciculata – cortisol
▪ zona reticularis – sex steroids
o source of adrenal steroids
o regulated by pituitary ACTH
- medulla
o composed of chromaffin cells
▪ neuroendocrine cells that provide an additional source of catecholamines (in
addition to the SYN)
▪ so when dealing with short term stress, its not just enough for the SYN to kick in,
we also have the adrenal medulla to make catecholamines
o secretion controlled by direct innervation; neuroendocrine
Adrenal Steroidogenesis
- this all occurs in the adrenal gland
- the precursor to all steroid hormones is cholesterol
- due to different intracellular enzymes in the adrenal cortex, cholesterol can be converted into
different hormones (depending on the activity of these intracellular enzymes)
- its the interplay and the activity of these intracellular enzymes which almost matters more than
the actual amount of the hormone produced
- steroidogenic enzymes are cytochrome p450s—e.g. CYP17
o dont need to memorize all the enzymes or the structure of the hormones just know that
all steroid hormones come from cholesterol and that the interconversion of hormones
occurs due to these cytochromes p450s enzymes which are found in the adrenal cortex
- these enzymes are found in membranes of mitochondria and ER
- energy comes from electron transport
find more resources at oneclass.com
find more resources at oneclass.com
Major Pathways for the Synthesis of Steroid Hormones in the Adrenal Cortex
HPA Axis
- hypothalamic-pituitary adrenal axis
- in response to systemic stress (long term stress) like cold, hypoglycemia, or fear, it stimulates
higher areas of the brain
- the hypothalamus will release corticotropin releasing hormone and via parvicellular cells it acts
on the CRH receptors in the ant pituitary which will release adrenocorticotrophin hormone
(ACTH)
- ACTH is a peptide hormone that will circulate the blood and bind to ACTH receptors in the
adrenal cortex
- This will elicit an increase in cortisol production
- If the levels of cortisol get too high in production, it causes a –ive feedback loop to shut down
production of CRH in the hypothalamus and ACTH in the ant pituitary
- Ultimately, cortisol will help raise blood glucose
o It also promotes gluconeogenesis in the liver and other organs
find more resources at oneclass.com
find more resources at oneclass.com
o It also causes muscle catabolism (break down proteins to liberate amino acids which
will be used by the liver to make more glucose)
o It will also inhibit GLUT4 activity in the muscle or adipose
▪ This will keep circulating glucose levels high to get to the brain
Adrenal Steroidogenesis
- ACTH comes from the ant pituitary
- It circulates and binds to ACTH receptors in the adrenal cortex
- How do we get an upregulation of cortisol in the adrenal cortex then?
- 4 things happen when ACTH binds to its receptor in the adrenal cortex:
o ACTH binds to its receptor (which is a GPCR)
o Activation of GPCR causes an increase in adenylyl cyclase activity to ultimately increase
intracellular cAMP
o This will activate cholesterolesterhydrolase (CEH) this will remove the esters from
cholesterol esters to liberate cholesterol
o Now we have cholesterol ready to go to be made by the adrenal cortex cells into
cholesterol
o Cholesterol is then brought into the mitochondria by steroid acute regulatory protein
(stAR)
o ACTH binds to its receptor and the following things occur:
1. Upregulation of the ACTH receptor itself further facilitating the feedforward
cascade making more cortisol bc there is more receptor to bind ACTH
2. Upregulation of CEH activity liberating more cholesterol
3. Increase stAR activity more cholesterol is brought into the mitochondria
(THIS IS THE RATE LIMITING STEP OF STEROID HORMONE SYNTHESIS)
4. It upregulates the receptor for low density lipoprotein (LDL)
• This is a precursor to cholesterol that can be brought it to ultimately
create cholesterol
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Adrenal steroidogenesis this all occurs in the adrenal gland the precursor to all steroid hormones is cholesterol. Major pathways for the synthesis of steroid hormones in the adrenal cortex. Acth is a peptide hormone that will circulate the blood and bind to acth receptors in the adrenal cortex. This will elicit an increase in cortisol production. If the levels of cortisol get too high in production, it causes a ive feedback loop to shut down production of crh in the hypothalamus and acth in the ant pituitary. Ultimately, cortisol will help raise blood glucose. It also promotes gluconeogenesis in the liver and other organs. It also causes muscle catabolism (break down proteins to liberate amino acids which will be used by the liver to make more glucose) It will also inhibit glut4 activity in the muscle or adipose: this will keep circulating glucose levels high to get to the brain.
