14.1 Endocrinology Flashcards
What is a hormone?
A chemical signal released from an endocrine cell to influence the activity of another cell via a receptor through a series of mechanisms
Compare endocrine, paracrine and autocrine communication
Endocrine: hormones travel through blood to effect distant cells
Paracrine: hormones act on neighbouring cells
Autocrine: hormones act on the same cell in a feedback loop (this is seen in hormones effecting breast cancer)
What are the different types of endocrine systems?
- Endocrine gland (well-defined collection of endocrine cells)
- Neuroendocrine systems (Neurons that release hormones both into the blood and into the CNS)
- Diffuse endocrine systems (endocrine cells not arranged in glands but are dispersed, this is seen in the gut, respiratory tract, heart, kidney and in fat)
What are the general functions of endocrine systems?
Promoting the survival of individuals and therefore species by effects on:
- development and growth, including differentiation of cells to result in functional organs and tissues
- maintaining homeostasis (constant stable internal environment, very long term)
- responding to stimuli that arise as a result of a changed external environment
- control of reproduction (e.g. gamete production and maturation is largely controlled by hormones)
How quick can endocrine reactions be and what do their response times depend on? Give examples.
- Can be anything from rapid (secs-mins) to intermediate (minutes) to prolonged (hours, days)
- Depends on rapidity of release, half-life of the hormone and rapidity of action/response
- > rapid example: adrenaline in fight or flight response, rapid release, T1/2 of ~10 secs, rapid action at receptors
- > intermediate example: insulin after eating a meal causing rapid uptake of glucose, has a rapid release and a short(ish) T1/2 of around 3-5 mins, but an intermediate action which prolongs the response over several minutes (60-90 mins)
- > long example: lung development after birth due to the hormone cortisol, produced from adrenal gland and causes production of lung surfactant, effects the genome through encouraging surfactant production with a T 1/2 of 90 mins and an action which lasts for hours (if baby premature, blue baby syndrome occurs as cortisol hasn’t been released yet so mother may be treated with cortisol before birth, if not produced at all with a normal birth then infant respiratory distress syndrome occurs as work done to breathe is far higher than it should be)
- What is a clinical way to determine disregulation?
- Hormones act in cycles
- Take regular samples throughout the day/at set intervals and then compare over a series of days to see whether patterns are regular or irregular or if they do or do not match certain events
What are the two types of control for endocrine systems?
- Feedforward (often stimulatory)
- Feedback (often negative/inhibitory)
What are the different chemical classifications of hormones (with examples)?
- Amino acid derived, e.g. T3, adrenaline
- Polypeptide, e.g. insulin
- Protein, e.g. prolactin
- Glycoproteins, e.g. luteinising hormone
- Steroids, e.g. testosterone (four rings, lipid soluble)
- Prostaglandins, e.g. prostaglandin E2 (cyclic fatty acids)
- Gaseous mediators, e.g. nitric oxide
Generally organised into two groups, hydrophobic/lipophilic or hydrophilic/lipophobic
How are polypeptide and protein hormones synthesised, stored and released?
- Translation of proteins occurs on the rough endoplasmic reticulum
- Processed and packaged by the Golgi apparatus, where it is then secreted by vesicles that have budded off of the cisternae
- Either form small clear vesicles or dense-cored vesicles
- > small clear vesicles are released via constitutive secretion, which has unregulated membrane fusion i.e. can happen randomly
- > dense-core vesicles are released via regulated secretion, where the vesicles require a hormone or transmitter signal before release
Compare constitutive and regulation secretion.
Constitutive:
- Proteins are not concentrated within the vesicles, and vesicles are not stored within the cell
- Contents are released as soon as they are produced
- Regulation is through the control of transcription, as this process cannot occurs if the proteins are not synthesised
- Seen in unpolarised cells and is the main form of secretion from tumour cells
- Growth hormones are also just released as soon as they are produced
Regulated:
- Proteins are highly concentrated within vesicles, many of these secretory vesicles are then stored within the cell
- In response to a stimulus (e.g. Ca2+ influx) the vesicles will secrete their contents very quickly via exocytosis
What is a good indicator of a secretory cell?
Lots of euchromatin/loose chromatin, so shows a high protein production and secretory action
What happens to protein hormones after secretion?
- Protease cleavage occurs at various dibasic sites
- Pre-prohormone in rough ER, pre- section is a signal peptide
- Exists as a prohormone within the Golgi apparatus (signal peptide section removed)
- > prohormones can contain several copies of the same hormone, e.g. pro-thyrotrophin-releasing protein (TRH) made in the hypothalamus
- > some endocrine cells can produce multiple active hormones from one prohormone, e.g. ProOpioMelanoCortin (POMC) made in the anterior pituitary
- In secretory vesicle or in the extracellular space, pro- section of the protein is cleaved off just leaving the active hormone and another peptide
How are catecholamines synthesised, stored and released?
- Adrenaline and noradrenaline are synthesised by the same pathway in adrenal medulla chromaffin cells
- Released by exocytosis in response to a stimulus (innervated)
- A and NA are synthesised from the amino acid tyrosine in the following steps:
-> tyrosine to L-DOPA, catalysed by the enzyme tyrosine hydroxylase (tetrahydrobiopterin as a cofactor)
-> L-DOPA to dopamine, catalysed by the enzyme DOPA decarboxylase (pyridoxal phosphate as a cofactor), dopamine is a neurotransmitter in the CNS
-> Dopamine to noradrenaline, catalysed by the enzyme dopamine beta-hydroxylase (ascorbic acid and oxygen as cofactors), noradrenaline is a neurotransmitter for the sympathetic nervous system
-> Noradrenaline to adrenaline, catalysed by the enzyme phenylethanolamine n-methyl transferase (PNMT), these enzyme is pretty much only expressed in the adrenal medulla (s-adenosylmethionine as a cofactor)
Takes 20h to make a full adrenaline vesicle
How are steroid hormones synthesised, stored and released?
- Made rapidly from cholesterol
- Enzymes that catalyse this process are stored in the mitochondria and smooth ER
- Cholesterol is from the lipid stores
- Sterols are not stored within the cell but are instead produced and released by diffusion or membrane transporter on demand
- Steroid producing cells contain drops of lipids, lots of mitochondria with tubular cristae/folds and smooth endoplasmic reticulum filling up the rest of the cell
- As steroid hormones are lipophilic, they cannot be stored in vesicles as they would just be able to diffuse out
- Testosterone is synthesised in the testes (* derivatives increase body muscle and strength)
- Oestrogen and progesterone are synthesised in the ovaries
- Cortisol and aldosterone are synthesised in the adrenal glands
How are prostaglandins synthesised, stored and released?
- Synthesised from lipids in the cell membrane
- Initially broken down by lipases into arachidonic acid, then by cyclooxygenase enzymes to produce PGG2
- > this is then converted into the different types of prostaglandins (e.g. prostaglandins E2, F2alpha, I2)
- Similar to leukotrienes and thromboxanes as also derived from arachidonic acid
- Prostaglandins are hydrophobic so cannot be stored in vesicles (would diffuse out), so are not stored in general but are produced and released upon demand
- Aspirin blocks prostaglandin receptors
- Prostaglandin E2 is used to induce labour/cause uterine contractions
