2 Introcuction To Endocrinology Flashcards
Q: What are the 3 different types of hormone?
A: protein/polypeptide, steroid (cholesterol precursor), miscellaneous (fit into neither category)
Q: What are nearly all protein/polypeptide hormones first made as? What form is this?
A: prohormones inactive form
Q: How do you liberate an active hormone from its prohormone? Outline.
A: cleaved
- endocytosed into the GA
- golgi adds enzymes to the vesicles
- vesicle then leaves GA and moves towards surface of cell
- cleavage of the pro-hormone by GA enzymes leads to generation of the active hormone
- vesicles filled with active hormone (e.g. ACTH) accumulate near the cell surface
- when a signal arrives, you get exocytosis and the ACTH is released into the blood. vesicles without signal are just storage sites
Q: How do you generally differentiate between a protein, polypeptide and oligopeptide?
A: protein= 50< aa, polypeptide= 50>, oligopeptide= 2-20
Q: What is the prohormone for ACTH?
A: pro-opiomelanocortin (POMC)
Q: How many amino acids make ACTH compared to its prohormone?
A: 39 vs 241
Q: Where is ACTH produced?
A: anterior pituitary
Q: What do all steroid hormones derive from?
A: cholesterol
Q: What is the major steroid hormone?
A: cortisol
Q: Outline the process by which protein/polypeptide prohormones are produced? (Specify for ACTH)
A: (0. aa enter cell (pituitary corticotroph cell))
- specific mRNA is synthesised within cell nucleus
- enters cyto
- attaches to ribosome (rough ER)
- translation of specific mRNA -> prohormone (POMC)
Q: Where do the amino acids needed for protein/polypeptide synthesis come from?
A: blood supply
Q: Which blood vessels are pituitary hormones secreted into?
A: (definitely capillary since they are closest to cell) pituitary capillary
Q: Outline the process by which steroid hormones are synthesised. (6)
A: 1. LDL rich in cholesterol= transferred into cell (endocytosis)
- cholesterol= split from lipoprotein and then esterified and stored in cytoplasmic vacuoles (fatty acid esters)- appear as fat droplets
- break down the fatty acid esters to liberate cholesterol using esterase enzyme
- cholesterol gets into the mitochondrion via StAR Proteins (Steroidogenic Acute Regulatory Proteins)
- within mitochondrion, there are lots of enzymes that allows the multi-step conversion of the cholesterol into the steroid hormone of choice
- leaves mito
Q: Which cell is cortisol produced in?
A: adrenal cortical cell
Q: Where are the adrenal glands in relation to the kidneys?
A: above
Q: What is the role of LDLs in steroid hormone production?
A: deliver cholesterol to cell
Q: What 2 structures produce most of our steroid hormones?
A: adrenal glands, gonads
Q: Where in a cell are steroid hormones made?
A: mitochondria
Q: What is the rate limiting step in steroid hormone synthesis? What happens if you don’t have enough? What happens when you have more?
A: StAR protein, body can’t produce all the steroid hormone needed, more cholesterol you can get into the mitochondrion and the more steroid hormone you can produce
Q: What determines the steroid hormone produced from cell to cell?
A: enzymes present determines the final steroid hormone product
Q: What occurs once a steroid hormone is made?
A: can freely diffuse across the cell membrane into blood (blood capillary)
not stored in cell since very lipid soluble (due to its cholesterol backbone)
Q: Would an RNA synthesis inhibitor cause a greater reduction in protein/polypeptide hormone or steroid production?
A: reduces both
protein/polypeptide reduced more
Q: Describe protein hormones. Lifetime in blood? What occurs when they’re needed?
A: degraded quickly (liver/things in blood will metabolise) which means short lifetime in blood
when needed-> released into blood (stored in vesicles before)
Q: Describe steroid hormones. Where are they stored? How?
A: blood
proteins are present in blood that bind to them- some are non-specific (more common plasma protein but weaker binding-loosely) and some are specific= specific binding globulin (less common plasma protein but stronger binding)
^ mixture of specific and non specific binding
Q: What is the specific binding globulin for cortisol?
A: CBG
Q: Where are cholesterol droplets common and what are they for? What do they look like?
A: steroid hormone producing cells
provide cholesterol to make steroid hormone
clear circular vacuoles
Q: What is albumin?
A: common plasma protein that binds non specifically to most steroid hormones
Q: What is the difference between bound and unbound/free steroid hormones?
A: free steroid hormone can enter tissue
Q: What is the relationship between bound and unbound/free steroid hormones? What can adjust this relationship? (2) 2 examples.
A: dynamic equilibrium
hormone + plasma protein protein bound hormone
- Uptake of steroid hormones by the tissue.
EXAMPLE: Cortisol is a stress hormone. At times of stress, more of the free cortisol enters the tissues and the concentration of free cortisol begins to fall. Some of the protein bound hormone releases to try and maintain the free steroid hormone levels in the blood + endocrine cells are stimulated to produce more of the steroid hormone (since the protein bound stores are low) - Rise in plasma protein levels. The more plasma proteins you have, the more likely it is that the plasma proteins are going to bind to steroid hormone and so more endocrine cell hormone synthesis and release The equilibrium is maintained.
EXAMPLE: Pregnancy - increases CBG levels (specific cortisol binding globulin) -> cortisol levels rise (more production and release) to ensure constant level of free hormone is available to tissues
Q: How do protein/polypeptide hormones signal and cause effects using ACTH as an example. (7)
A: most are G-protein
- ACTH (doesn’t diffuse easily into cell) binds to G-protein coupled receptor (specific receptor exists for each protein/polypeptide- really high affinity which is important since in low concentration)
- dissociation of alpha subunit of G-protein from beta, gamma subunits
- leads to activation of adenylate cyclase which converts ATP -> cAMP
- Increase in cAMP activates Protein Kinase A which causes…
- cholesterol esterase to be phosphorylated which means it’s activated -> goes on to liberates cholesterol
- StAR protein (also phosphorylated and activated) mediates transfer of cholesterol into mitochondria
- This stimulates steroid hormone production- cortisol
Q: Give an example of a protein/polypeptide hormone and what cell it acts on. Effect?
A: ACTH acting on adrenal cortical cells to produce cortisol
Q: How do steroid hormones signal and cause effects using cortisol as an example. (5)
A: Only free steroid hormones can get into cells- very lipid soluble so can diffuse through the membrane
- free cortisol enters cell by passive diffusion
- binds to specific INTRACELLULAR RECEPTOR- glucocorticoid (GC) in cell cytoplasm
- Once bound to the receptor, they translocate (complex) to the nucleus
- binds to specific DNA binding sites
- leads to changes in transcription rates of specific genes and production of mRNA (increases or decreases)
(translation of mRNA to protein within endoplasmic reticulum)
Q: Why do steroid hormones have a massive effect? Speed?
A: by changing the protein machinery within the cell-
massive effect on DNA Transcription and subsequent translation
effects are slow since there’s a lot of steps
Q: What is the relationship between hormones and homeostasis? Why is this relevant to negative feedback?
A: generally, endocrine hormones are released as part of a homeostatic process - the body will releases endocrine hormones for some adaptive reason
Once you’ve dealt with the issue you need to switch off the hormone and return it to baseline levels- the hormone switches off its own production
Q: Give an example of negative feedback using hormones. (5)
A: EXAMPLE: ATCH/Cortisol
- Anterior pituitary is stimulated by stress
- Protein/polypeptide hormone ACTH is released
- ACTH acts on the adrenal gland to increase cortisol production
- Cortisol enters the bloodstream and carries out its function to decrease stress
- Cortisol returns to the anterior pituitary and switches ACTH off (end consequence is that Cortisol production is also switched off)
Q: What are the 2 hormones that cause positive feedback?
A: LH and Oestrogen
Q: Which target would cortisol bind to induce negative feedback within the anterior pituitary?
- albumin
- cholesterol
- glucocorticoid receptor
- protein kinase A
- StAR protein
A: glucocorticoid receptor
