Introduction to endocrinology Flashcards by Salma Khan

Endocrine gland?

group of cells which secrete messenger molecules directly into the bloodstream

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Hormone?

bioactive messenger molecule secreted by endocrine gland into blood (not a metabolite of energy substrate)

effects a change

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What did Bayliss and Starling demonstrate?

pancreatic secretion not under neural control, hormonal control important

secretin released from duodenal S cells stimulated pancreas to secrete HCO3

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What did Banting and Best demonstrate?

extracted and purified insulin from the pancreas

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Endocrine?

hormone acts on target cells at a distance from source via bloodstream

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Paracrine?

hormone acts on nearby target cells

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Autocrine?

hormone acts on own immediate source

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Differences between endocrine and NS messengers?

release of chemical into bloodstream vs across a synapse

effect generalised vs localised to innervated target cells

long time span (s to days) vs milliseconds because NT broken down very quickly

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What are the 3 classifications of hormones?

protein/polypeptide

steroid

miscellaneous

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What are protein polypeptide hormones?

more complex structure

complex (LH -200aa)
intermediate (insulin)
small (TRH-3aa)
dipeptides (T4 derived from 2 iodinated tyrosine residues)
derived from single aa (catecholamines)

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What are steroid hormones?

derived from steroid cholesterol

intact steroid nucleus (adrenal/gonadal steroid)
broken steroid nucleus (Vit D and metabolites)

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What are miscellaneous hormones?

hormone with protein structures (e.g. thyroid hormones have iodine incorporated - not protein specific)

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What provides amino acids to synthesise protein hormones?

blood supply

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Describe the synthesis, storage and secretion process of a protein hormone (ACTH) ?

pro-hormone transcribed from DNA
mRNA moves into cytoplasm and binds to rER
mRNA is translated on ribosome of rER and endocytosed into Golgi
proteolytic enzymes added to pro-hormone vesicles to cleave pro-hormone into its active form
vesicles containing hormone accumulate near cell surface and when signal arrives they are exocytosed and released into blood

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Why are polypeptide hormones short lasting?

quickly metabolised in the blood when unbound

broken down in the liver

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What is ACTH?

produced by anterior pituitary
from POMC pro-hormone
stored in pituitary corticotroph cells

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What are hormones produced by anterior pituitary?

polypeptide hormones

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What is POMC?

pro-opiomelanocortin
241 amino acids
pro hormone of ACTH

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Describe the synthesis, storage and secretion process of steroid hormones?

cholesterol delivered to cells via LDLs that diffuse passively across cell membrane
cholesterol stored as fatty acid esters (appear as fat droplets)
cholesterol moves into mitochondria by StAR protein
enzymes allow stepwise conversion of cholesterol into steroid hormone

What changes within steroid hormone producing cells?

balance of enzymes differs depending on hormone being produced

there is a divergence of pathways due to differing enzymes that drives the precursor down a different route

How to distinguish steroid producing cells?

lots of fat droplets (cholesterol stores as fatty acid esters)
e.g. in adrenal glands/gonads

What is the RATE LIMITING STEP and what increases its rate?

the cholesterol moving into the mitochondria by StAR protein

more StAR –> more cholesterol in mitochondria –> more steroid hormone produced

What are the differences in steroid and protein hormone production?

Protein hormones stored in vesicle in cell and await stimulus for exocytosis - steroid hormones are lipid soluble and are secreted into the blood stream as soon as they are produced

Protein uses DNA to transcribe mRNA for further processing in rER whilst steroid does not use DNA in nucleus –> use mitochondria to convert cholesterol to hormone

Steps in conversion of cholesterol to cortisol?

cholesterol
preognenolone (P450scc)
17 a pregnenolone (P450c17)
17 a progesterone (3BHSD)
11 deoxycortisol (P450c21)
cortisol (P450c11B)

How are protein hormones transported?

stored in tissues that produce them until stimulated to be exocytosed secreted into the blood travel unbound to site of action

What is the consequence of protein hormones travelling unbound?

sensitive to enzymatic breakdown | very short half life (mins)

How are steroid hormones transported?

stored in blood bound to plasma proteins | small amounts of free steroid can move into tissues

What is an example of a steroid hormone binding protein?

these are large globular proteins that cannot freely cross the cell membrane albumin high amount in the plasma weakly binds all steroid proteins specific binding proteins (corticosteroid binding globulin, CBG for cortisol)

What must be ensured in the blood for steroid hormones?

a dynamic equilibrium between bound and free hormone free hormone + plasma protein -->/< [protein bound hormone

Availability of what must be a constant value for tissues?

free hormone adjust secretion rates of hormone by endo/exocrine cells to ensure changes to free hormone /plasma protein levels are corrected

What happens with a change in uptake of steroid hormone by tissue?

change in free hormone stress --> free cortisol enters tissues --> [] in blood decreases protein bound hormone releases to maintain [] if more taken up, endocrine cells stimulated to produce more hormone

What is the use of the plasma protein in the blood?

reservoir to protect against rapid protein changes

What happens if there is an increase in plasma protein?

more likely to bind to free hormone and increase [] of protein bound hormone in pregnancy increase in CBG endocrine cells increase hormone synthesis to maintain free cholesterol in the blood

What does the capacity of a cell to respond to a hormone depend on?

presence of receptors | receptors need high specificity and affinity if the hormone is low in []

How do protein hormones work? | ACTH example

ACTH influences cortisol production via G-protein coupled receptors ACTH binds to Gs protein coupled receptor dissociation of a from g and b subunits adenylate cyclase activated cAMP production from ATP increases cAMP activates PKA esterase phosphorylated (activated) to convert cholesterol esters to free cholesterol StAR protein phosphorylated to mediate transfer of cholesterol to mitochondria stimulate steroid hormone production

Why is a protein receptor (ACTH receptor) needed to recognise ACTH hormone?

protein is not lipid soluble and so the protein receptor is needed to recognise the protein

What is the function of ACTH generally?

stimulate cortisol production

What does the biological response of a cell to receptors depend on?

the number of receptors on target cell (these are saturable) [] hormone affinity of hormone-receptor interaction

How do steroid hormones work?

only free steroid hormones enter cells as they are lipid soluble diffuse through membrane bind to intracellular receptors in the cytoplasm and nucleus bound complex (steroid-receptor complex) translocated to nucleus to affect DNA transcription hormone is then eliminated from the cell unoccupied receptor reestablished

What do steroid hormones bind to in nucleus?

bind to DNA binding sites (Respose Elements)

What is closed loop hormone feedback?

hormone produced by peripheral target organ feeds back to organ that stimulates it to control its function e.g. thyroid --> hypothalamus adrenal glands --> pituitary

What is negative feedback?

hormone switched off its own production

Give an example of negative feedback?

stress activates anterior pituitary ACTH released from corticotroph cells ACTH acts on adrenal gland to increase cortisol production cortisol enters blood stream and functions to decrease stress cortisol returns to anterior pituitary switch off ACTH cortisol switched off

Given an example of positive feedback?

LH and oestrogen

Via what does ACTH act on adrenal glands?

G protein coupled receptors

Via what does cortisol act on anterior pituitary?

glucocorticoid receptors