2 Introcuction To Endocrinology

Question 1

Q: What are the 3 different types of hormone?

Answer 1

A: protein/polypeptide, steroid (cholesterol precursor), miscellaneous (fit into neither category)

Question 2

Q: What are nearly all protein/polypeptide hormones first made as? What form is this?

Answer 2

A: prohormones inactive form

Question 3

Q: How do you liberate an active hormone from its prohormone? Outline.

Answer 3

A: cleaved

1. endocytosed into the GA
2. golgi adds enzymes to the vesicles
3. vesicle then leaves GA and moves towards surface of cell
4. cleavage of the pro-hormone by GA enzymes leads to generation of the active hormone
5. vesicles filled with active hormone (e.g. ACTH) accumulate near the cell surface
6. when a signal arrives, you get exocytosis and the ACTH is released into the blood. vesicles without signal are just storage sites

Question 4

Q: How do you generally differentiate between a protein, polypeptide and oligopeptide?

Answer 4

A: protein= 50< aa, polypeptide= 50>, oligopeptide= 2-20

Question 5

Q: What is the prohormone for ACTH?

Answer 5

A: pro-opiomelanocortin (POMC)

Question 6

Q: How many amino acids make ACTH compared to its prohormone?

Answer 6

A: 39 vs 241

Question 7

Q: Where is ACTH produced?

Answer 7

A: anterior pituitary

Question 8

Q: What do all steroid hormones derive from?

Answer 8

A: cholesterol

Question 9

Q: What is the major steroid hormone?

Answer 9

A: cortisol

Question 10

Q: Outline the process by which protein/polypeptide prohormones are produced? (Specify for ACTH)

Answer 10

A: (0. aa enter cell (pituitary corticotroph cell))

1. specific mRNA is synthesised within cell nucleus
2. enters cyto
3. attaches to ribosome (rough ER)
4. translation of specific mRNA -> prohormone (POMC)

Question 11

Q: Where do the amino acids needed for protein/polypeptide synthesis come from?

Answer 11

A: blood supply

Question 12

Q: Which blood vessels are pituitary hormones secreted into?

Answer 12

A: (definitely capillary since they are closest to cell) pituitary capillary

Question 13

Q: Outline the process by which steroid hormones are synthesised. (6)

Answer 13

A: 1. LDL rich in cholesterol= transferred into cell (endocytosis)

2. cholesterol= split from lipoprotein and then esterified and stored in cytoplasmic vacuoles (fatty acid esters)- appear as fat droplets
3. break down the fatty acid esters to liberate cholesterol using esterase enzyme
4. cholesterol gets into the mitochondrion via StAR Proteins (Steroidogenic Acute Regulatory Proteins)
5. within mitochondrion, there are lots of enzymes that allows the multi-step conversion of the cholesterol into the steroid hormone of choice
6. leaves mito

Question 14

Q: Which cell is cortisol produced in?

Answer 14

A: adrenal cortical cell

Question 15

Q: Where are the adrenal glands in relation to the kidneys?

Answer 15

A: above

Question 16

Q: What is the role of LDLs in steroid hormone production?

Answer 16

A: deliver cholesterol to cell

Question 17

Q: What 2 structures produce most of our steroid hormones?

Answer 17

A: adrenal glands, gonads

Question 18

Q: Where in a cell are steroid hormones made?

Answer 18

A: mitochondria

Question 19

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?

Answer 19

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

Question 20

Q: What determines the steroid hormone produced from cell to cell?

Answer 20

A: enzymes present determines the final steroid hormone product

Question 21

Q: What occurs once a steroid hormone is made?

Answer 21

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)

Question 22

Q: Would an RNA synthesis inhibitor cause a greater reduction in protein/polypeptide hormone or steroid production?

Answer 22

A: reduces both

protein/polypeptide reduced more

Question 23

Q: Describe protein hormones. Lifetime in blood? What occurs when they’re needed?

Answer 23

A: degraded quickly (liver/things in blood will metabolise) which means short lifetime in blood

when needed-> released into blood (stored in vesicles before)

Question 24

Q: Describe steroid hormones. Where are they stored? How?

Answer 24

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

Question 25

Q: What is the specific binding globulin for cortisol?

Answer 25

A: CBG

Question 26

Q: Where are cholesterol droplets common and what are they for? What do they look like?

Answer 26

A: steroid hormone producing cells provide cholesterol to make steroid hormone clear circular vacuoles

Question 27

Q: What is albumin?

Answer 27

A: common plasma protein that binds non specifically to most steroid hormones

Question 28

Q: What is the difference between bound and unbound/free steroid hormones?

Answer 28

A: free steroid hormone can enter tissue

Question 29

Q: What is the relationship between bound and unbound/free steroid hormones? What can adjust this relationship? (2) 2 examples.

Answer 29

A: dynamic equilibrium hormone + plasma protein protein bound hormone 1. 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) 2. 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

Question 30

Q: How do protein/polypeptide hormones signal and cause effects using ACTH as an example. (7)

Answer 30

A: most are G-protein 1. 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) 2. dissociation of alpha subunit of G-protein from beta, gamma subunits 3. leads to activation of adenylate cyclase which converts ATP -> cAMP 4. Increase in cAMP activates Protein Kinase A which causes... 5. cholesterol esterase to be phosphorylated which means it's activated -> goes on to liberates cholesterol 6. StAR protein (also phosphorylated and activated) mediates transfer of cholesterol into mitochondria 7. This stimulates steroid hormone production- cortisol

Question 31

Q: Give an example of a protein/polypeptide hormone and what cell it acts on. Effect?

Answer 31

A: ACTH acting on adrenal cortical cells to produce cortisol

Question 32

Q: How do steroid hormones signal and cause effects using cortisol as an example. (5)

Answer 32

A: Only free steroid hormones can get into cells- very lipid soluble so can diffuse through the membrane 1. free cortisol enters cell by passive diffusion 2. binds to specific INTRACELLULAR RECEPTOR- glucocorticoid (GC) in cell cytoplasm 3. Once bound to the receptor, they translocate (complex) to the nucleus 4. binds to specific DNA binding sites 5. leads to changes in transcription rates of specific genes and production of mRNA (increases or decreases) (translation of mRNA to protein within endoplasmic reticulum)

Question 33

Q: Why do steroid hormones have a massive effect? Speed?

Answer 33

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

Question 34

Q: What is the relationship between hormones and homeostasis? Why is this relevant to negative feedback?

Answer 34

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

Question 35

Q: Give an example of negative feedback using hormones. (5)

Answer 35

A: EXAMPLE: ATCH/Cortisol 1. Anterior pituitary is stimulated by stress 2. Protein/polypeptide hormone ACTH is released 3. ACTH acts on the adrenal gland to increase cortisol production 4. Cortisol enters the bloodstream and carries out its function to decrease stress 5. Cortisol returns to the anterior pituitary and switches ACTH off (end consequence is that Cortisol production is also switched off)

Question 36

Q: What are the 2 hormones that cause positive feedback?

Answer 36

A: LH and Oestrogen

Question 37

Q: Which target would cortisol bind to induce negative feedback within the anterior pituitary? - albumin - cholesterol - glucocorticoid receptor - protein kinase A - StAR protein

Answer 37

A: glucocorticoid receptor