What is an endocrine gland?
- Group of cells
- Secrete messenger molecules
- Directly into bloodstream
What is a hormone?
- Bioactive “messenger” molecule
- Secreted by endocrine
- Into blood
Contrast Endocrine vs Paracrine vs Autocrine
- Endocrine = hormone action on target cells at a distance from source
- Paracrine = hormone action on nearby target cells
- Autocrine = hormone having effect on own immediate source
What are the 3 classifications of hormones?
- Protein/polypeptide hormones
- Steroid Hormones
- Miscellaneous
Where are Protein Hormones (PH) synthesised?
ER
What determines the amino acid sequence in all peptides?
Specific mRNA synthesised in nucleus (mRNA sequence dictated by specific gene)
Pre / Prepro-hormone is larger than active hormone?
Yes
What is the precursor molecule to steroid hormones?
Cholesterol
Describe how protein hormone is synthesised. (6)
- mRNA synthesised within cell nucleus
- mRNA translated into pro hormone in ER
- Prohormone transported to Golgi.
- In Golgi, pro hormone packaged into vesicles (containing proteolytic enzymes).
- Prohormone cleaved within the vesicle, generates active hormone.
- Vesicles move near cell surface, and are exocytosed out of the cell when a signal arrives.
Where do the amino acids supplying for PH synthesis come from?
The blood capillary.
How are steroid hormones synthesised?
- LDLs transported into cell (containing cholesterol).
- LDLs stored as fatty acid esters.
- When SH being produced, esterase enzymes break down fatty acid esters - liberates cholesterol.
- Cholesterol enters mitochondrion via StAR proteins.
- Enzymes within StAR protein convert SH into SH of choice.
- SH passively diffuses out of cell.
What allows SH to passively diffuse out of cells?
They are highly lipid soluble.
All of the APG hormones are polypeptides? True or false
True
What produces most SH?
Adrenal Glands or Gonads.
What is the rate limiting step in SH synthesis?
StAR protein transporting cholesterol into the mitochondria.
Which type of hormones are able to circulate freely within the bloodstream?
PH, because they are water soluble.
What is the dynamic eqm formed for SH?
Free Hormone + Plasma Protein <===> Plasma Bound Hormone
What is the purpose of SH forming a dynamic eqm?
Buffer hormones and serve to protect against rapid changes in hormone concentration.
Only free hormone is biologically active in the dynamic eqm. T or F?
True
Plasma proteins such as Albumin selectively bind to SH. T or F?
False
How does binding capacity affect hormone clearance rate?
Greater binding capacity = Slower clearance rate of the hormone
Why must a receptor have a high affinity and specificity for a particular hormone?
Because hormones are only present in very small concentrations
3 factors that determine the biological response of a target cell?
- Concentration of hormone in circulation
- Concentration / number of receptors
- Affinity of hormone-receptor interaction.
Explain mechanism of hormone action (hormone signalling) for PH. (7)
- Receptor (e.g. ACTH receptor) binds to PH.
- ACTH binding to ACTH receptor activates Adenylate Cyclase.
- Adenylate Cyclase causes increase in cAMP production.
- Increased cAMP activates Protein Kinase A.
- Esterase is phosphorylated - liberates cholesterol.
- StAR protein also phosphorylated - allows cholesterol to move into mitochondria.
- Therefore, PH drives SH synthesis.
Why do PH have a very short half life?
Because they travel unbound.
Explain mechanism of action (hormone signalling) of SH. (5)
- Free hormone passively diffuses into cell.
- SH bind to intracellular receptors.
- Hormone-receptor complex translocates to nucleus - binds to DNA binding site.
- Changes DNA transcription rates/mRNA production.
- SH has a powerful effect as it changes protein machinery within the cell.
What is negative feedback?
- Closed Loop System
- Hormone switches off its own production
Which is more common for endocrine function: negative feedback or positive feedback?
Negative Feedback.
Give an example of positive feedback.
LH and Oestrogen.