PHAR 300 Lecture Notes - Lecture 19: Prostaglandin, Macrophage, Protein Catabolism
7 Jun 2018
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PHAR300
Corticosteroids : anti inflammatory agents
Endocrine system
-autocrine, paracrine and endocrine (acts on remote targets) signalling mechanisms
Hormones
-chemical messenger that circulates in the body and has an effect on distant cells
-hormone in the circulation reaches target cells with specific receptors, communicate via the
circulation
-remote form of communication : send messages, store things far away and react to them
-major players :
-central control is in the brain : hypothalamus (= basic controller) sends messages through
the portal circulation to anterior pituitary (posterior does other things : it secretes
oxytocin, vasopressin into the blood system) -> send messages (ACTH, GH, TSH, LH and
FSH) to other endocrine tissues throughout the body (thyroid, parathyroid, pancreas, adrenal
glands, ovaries and testes)
-lots of targets => tailor the receptor to make it specific
-different responses in the anterior pituitary => different hormones
-CRF (also CRH) : corticotrophin releasing factor is an important one, released by hypothalamus,
goes to the anterior pituitary
-anterior pituitary then releases ACTH (adrenocorticotrophic hormone) acts on adrenal
cortex -> produces steroids, one of which is cortisol
-CRF : processed peptides which can make proteins ; 41 AA ; prohormone -> can be
irreversibly cut off and we end up with active hormones ; specifically controlled (right amount
made at the right time) to produce CRF
-CRF acts on G protein coupled receptors in the anterior pituitary to stimulate POMC
(proopiomelanocorticotropin) synthesis -> coupled to other proteins, one of which produces
cAMP -> when activate it => stimulate increase of cAMP, and affect synthesis of specific
products (e.g. POMC -> increase its transcription) -> get processed to make hormones and
then secrete it (e.g. ACTH and beta-LPH)
-cleavages on POMC can produce ACTH
-peptide which will interact with a specific hormone in the adrenal gland
-adrenal gland : on top of the kidney
-core part : medulla ; outside part : cortex
-ACTH receptor in the cortex -> stimulate cells in the cortex to produce hormones like
cortisol (steroid hormone, 4 rings, lipophilic, bound to proteins in liquid medium, that
transport it around)
-ACTH stimulates specific reactions => enhance production of steroids ; increase delivery
of cholesterol to the inner mitochondrial membrane (precursor to make steroids) ; increase
transcription of steroidogenic enzymes (e.g. P450 side chain cleavage enzyme CYP11A1)
-if we cleave cholesterol and release the chain -> can go along the pathway to make steroids
-> ACTH increases transcription of the enzyme that makes the cleavage
-ACTH regulates glucocorticoid synthesis in the zonae fasciculata / reticularis (special
P450 like CYP11B1 and CYP17 will push the reaction to make cortisol here)
-aldosterone (mineralocorticoid - controls water and salt in the body, comes from zona
Glomerulosa) ; glucocorticoid (controls things like glucose) ; DHEA (precursors for
androgens, made in the medulla by CYP17)
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Document Summary
Autocrine, paracrine and endocrine (acts on remote targets) signalling mechanisms. Chemical messenger that circulates in the body and has an effect on distant cells. Hormone in the circulation reaches target cells with speci c receptors, communicate via the circulation. Remote form of communication : send messages, store things far away and react to them. Fsh) to other endocrine tissues throughout the body (thyroid, parathyroid, pancreas, adrenal glands, ovaries and testes) Lots of targets => tailor the receptor to make it speci c. Different responses in the anterior pituitary => different hormones. Crf (also crh) : corticotrophin releasing factor is an important one, released by hypothalamus, goes to the anterior pituitary. Anterior pituitary then releases acth (adrenocorticotrophic hormone) acts on adrenal cortex -> produces steroids, one of which is cortisol. Peptide which will interact with a speci c hormone in the adrenal gland. Adrenal gland : on top of the kidney. Core part : medulla ; outside part : cortex.
