Introduction to Endocrinology (1) Flashcards
what groups are hormones classified into
protein/polypeptide hormones. steroid hormones. miscellaneous
ENDOCRINE GLAND
a group of cells which secret “messenger” molecules directly into the bloodstream
ENDOCRINOLOGY
study of endocrine glands and their secretions
HORMONE
the bioactive “messenger” molecule secreted by an endocrine gland into the blood, i.e. not simply a
metabolite or energy substrate
ENDOCRINE
relates to hormone’s action on target cells at a distance from source
CRYPTOCRINE
a term devised to indicate that a hormone can have an effect within its own cell of production, i.e. hidden
AUTOCRINE
relates to hormone having an effect on its own immediate source
PARACRINE
relates to hormone’s action on nearby target cells e.g. within immediate area around source
Factors of endocrine system
Release of chemical (HORMONE) into bloodstream. Effect can be on many target cells spread throughout the body. Effect will take place over a relatively long time span ranging from seconds to days
Factors of the nervous system
Release of chemical (NEUROSTRANSMITTER)
across synapse. Effect will be restricted to those target cells actually innervated. Effect will be generated within millisecond
What are the classic endocrine glands
Gonads. Pancreas. Adrenals. Thyroid. Parathyroids. Pituitary
Where is Adrenocorticotropic Hormone (ACTH) produced and what is it initially produced as
Produced in corticotroph cells in the anterior pituitary. These hormones are usually produced as prohormones which are cleaved to generate the hormone. Prohormone of ACTH: Pro-opiomelanocortin (POMC)
An example of a protein/polypeptide hormone
Adrenocorticotropic Hormone (ACTH)
How are protein/polypeptide hormone synthesised
The blood supply provides amino acids which can be used to synthesise the hormone. Chosen pro-hormone is transcribed from the DNA and the mRNA moves into the cytoplasm and bind to the rER. Pro-hormone is endocytosed into the Golgi apparatus. Golgi adds enzymes to the vesicles containing the pro-hormone which cleave the pro-hormone. Cleavage of the pro-hormone 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.
What are steroid hormones produced from and where are most of them made
All produced from cholesterol - so cholesterol needs to be delivered to the cell. Most steroid hormones are produced by the Adrenal Glands or the Gonads
How are steroid hormones synthesised
LDLs are delivered to the adrenal cortical cell and are stored as Fatty Acid Esters (seen as fat droplets). Fatty acid esters are broken down by esterase to liberate cholesterol. Cholesterol enters mitochondrion via StAR proteins (Steroidogenic Acute Regulatory Protein) as the double membrane is aqueous. Here there are lots of enzymes that allows the step-wise conversion of the cholesterol into the steroid hormone of choice. The enzymes present in certain cells determines the final steroid hormone product (e.g. adrenal cortical cells have a set of enzymes that produced cortisol). The hormone is then secreted into the cytoplasm and then the blood.
What is the rate limiting step in steroid hormone production
Cholesterol then needs to be transported into the mitocondria by StAR protein. The more StAR proteins you have, the more cholesterol you can get into the mitochondrion and the more steroid hormone you can produce
Difference between polypeptide hormone and steroid hormone synthesis
Protein/polypeptide hormones are stored in vesicles in the cell, awaiting a stimulus triggering exocytosis. Steroid hormones are secreted into the blood stream as soon as they are produced - they’re very lipid soluble
Transport of protein/polypeptide hormones
Protein/polypeptide hormones are secreted into the blood and travel unbound to the site of action. Therefore they have very short half life (minutes). They are stored in the tissues that produce them. They aren’t bound to any plasma proteins in the blood so they are sensitive to enzymatic break down.
Transport of steroid hormones
Stored in the blood. Most steroid hormone are bound to plasma proteins in the blood. E.g. Albumin - present in large amount in the plasma - it can mop up a large amount of most steroid hormones but the interaction isn’t very specific. For each individual steroid hormone there tends to be a fairly specific plasma protein which forms a much stronger binding (e.g. Cortisol - Corticosteroid Binding Globulin (CBG)). There is a small amount of free steroid hormone in the blood.
Which type of steroid hormone can move into tissue
If the steroid hormone is bound to a plasma protein then it is not leaving the blood stream - only free steroid hormone can move into the tissues
Equilibrium of plasma protein bound and unbound steroid hormone in the blood:
At any given point you have a certain amount of hormone and plasma protein and a lot of protein bound hormone.
How does the equilibrium shift when there is an uptake of steroid hormone into the tissue
At times of stress, more of the free cortisol enters the tissues and the concentration of free cortisol begins to fall. Some of the hormone releases from the plasma protein to try and maintain the free steroid hormone levels in the blood. If the tissues start to use up more steroid hormone - it stimulates the endocrine cells to produce more of the steroid hormone
How does the equilibrium shift when there is a 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 protein bound hormone is formed. E.g. Plasma proteins that bind to cortisol rise massively during pregnancy. This sends a message to the endocrine cells to increase steroid hormone synthesis. This maintains the level of free cholesterol in the blood
What is the mechanism of action of ACTH (Protein /Polypeptide Hormone)
ACTH influences the production of steroid hormone cortisol. Protein/polypeptide hormones aren’t generally lipid soluble so you need a protein receptor to recognise the hormone - ACTH G-protein coupled receptor (in the adrenal gland). Binding of ACTH to the ACTH receptor activates Adenylate Cyclase which causes an increase in cAMP production from ATP. Increase in cAMP activates Protein Kinase A. Esterase is phosphorylated which liberates cholesterol. This stimulates steroid hormone production
How is the StAR protein activated
phosphorylation of StAR Protein activates the StAR Protein - allowing cholesterol to move into the mitochondrion
What is the mechanism of action of steroid hormones
Only free steroid hormones can get into cells. They are very lipid soluble so can diffuse through the membrane. They bind to intracellular receptors. Once bound, they translocate to the nucleus and have a massive effect on DNA Transcription and subsequent translation. Steroid hormone have a massive effect by changing the protein machinery within the cell
What is negative feedback in terms of hormone feedback
Negative Feedback is when the hormone switches off its own production. Endocrine hormones are released as part of a homeostatic process once you’ve dealt with the issue you need to switch off the hormone and return it to baseline levels.
Give an example of hormone negative feedback
Anterior pituitary is stimulated by stress. 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).
