Extra Info Flashcards
Endocrine
acts at a distance rom release site
Exocrine
secreted outside body (e.g. mammary gland, lumen)
Paracrine
acts on nearby cells
Autocrine
acts on its own secreting cells
Neuroendocrine
synthesized by nervous tissue and carried in blood
Neurocrine
released by nervous cells in contact with target cells
Properties used to define hormones
- produced by specific cells to act on target tissues
- hormone levels higher in blood draining gland
- determination of origin - surgical removal or destruction of producing cells –> altered physiological state
- reversal of effects - graft of gland or treatment with producing cell extracts correct abnormalities
- purification of producing cell extract increases potency (specific activity)
Hormone synthesis, release, mode of action and metabolism are based on?
Structure
4 classifications of hormones
- polypeptides, proteins, glycoproteins
- steroid
- amino acid derivatives (thyroid)
- fatty acid derivatives or eicosanoids (prostaglandin)
Protein hormones
- made and stored in granules and free to use when triggered
- products of genes
- water soluble (depending on AA make up) - not lipid soluble so need to be packaged
- accumulate in golgi vesicles and secreted via exocytosis
Steroid hormones
- stepwise conversion of cholesterol –> enzyme: cytochrome P450 family
- lipid soluble
- ABCD rings
Amino acid derivatives - thyroid
- generally derived from tyrosine and Trp
Fatty acid derivatives= eicosanoids
- derived from cell membranephospholipids (arachidonic acid)
- produced locally (autocrine and paracrine effects)
- synthesis via cyclooxyrgenase inhibited by NSAIDs
Classifications of eicosanoids
prostaglandins
prostacyclin
thromboxanes
leukotrienes
Factors involved in control of hormone release
- hormone structure
- lipophilic vs. water soluble (secretion, circulation)
Lipophilic = steroid, thyroid
- bound to carrier proteins
- bind to intracellular receptors
Water soluble = protein, catecholamines
- gene transcription, intracellular trafficking –> packaged and secreted in vesicles via exocytosis (degraded by peptidases)
- circulate free (except IGF-1)
- bind to surface receptors (require second messengers)
- protein vs. non-protein (de novo synthesis, enzyme activation)
General mechanism of action for cell surface receptors
- hormone binds to receptor on outside of cell
- kinase activated inside cell
- intracellular proteins phosphorylated –> activity altered to produce response
Termination of hormone action includes
Immediate effects = enzyme activation, exocytosis (triggered events)
Slow effects = stimulation of gene transcription, de novo protein synthesis
Signalling proteins are de-phosphorylated (by phosphatase) after signalling
R-H complex is internalized
- degraded
- dissociated –> receptor is recycled to cell surface
What is the major integration centre of the body?
hypothalamus
- regulates autonomic nervous system
- regulates most of the endocrine system
- processes all sensory info from baroreceptors, osmoreceptors and other external stimuli
pituitary stalk contains the?
hypothalamic-pituitary portal venous system
- deliver hypothalamic hormones to anterior pituitary
What is the function of GH
Direct effects
- stimulates lipolysis and reduces lipogenesis in adipose tissue = catabolic
- promotes synthesis of protein = anabolic
Indirect effects
- stimulating synthesis of IGF-1 and its binding proteins in liver –> cell growth
What is the function of TSH
- binds to its G-coupled receptor on membrane of follicular cells in thyroid gland
- stimulates cAMP pathway –> stimulates endocytosis of Tgb-I2 and synthesis of steroid hormones
What is the function of ACTH
stimulates mobilization of cholesterol in adrenal cortex –> more P450 –> increased release of corticosteroids
What is the function of LH?
In males: stimulates testosterone production by Leydig cells in the testis
In females: surge at ovulation
What is the function of FSH?
In males: stimulates secretion of inhibin by sertoli cells to regulate spermatogenesis
In females: development of follicles and secretion of estradiol
What is the function of prolactin?
stimulates synthesis of milk proteins (casein, lactalbumin)
in poultry - inhibition and maintenance of incubation behaviour = broodiness
Where do hypothalamic neurons receive info from?
- higher brain centres, emotions
- exterior, environmental and social stimuli
- internal rhythms
- metabolic state (temp., energy level, osmolarity)
- endogenous hormones by feedback
What regulates pulsatility of hormone release?
biological clock of hypothalamic suprachiasmatic nucleus
What controls hormone release from posterior pituitary?
direct nervous stimulation
what is the function of oxytocin?
causes contraction of myoepithlial cells for milk let down in the mammary gland and in the myometrium for contraction of the uterus for parturition
What is the function of vasopressin (ADH)?
stimulate reabsorption of water from distal tubular kidney to maintain blood osmolarity
What controls hormone release in the anterior pituitary?
controlled by releasing and release inhibiting factors delivered from hypothalamus by the hypothalamic-hypophyseal portal system
Which hormones regulate metabolism?
GH, TSH, MSH, ACTH, beta-LPH
Which hormones regulate reproduction?
LH, FSH, TSH and prolactin
What must you consider when choosing a model system?
Use the most simple and well defined system possible that will achieve your objectives, considering the advantages and disadvantages
What is an isolated perfused organ system used to determine?
the overall metabolic effects on a particular organ
When are in vitro models useful?`
for studying details of particular biochemical pathways involved in the endocrine effects on specific tissues/cell types
- cell culture systems – primary cells or immortalized cell lines
- culture conditions are critical
What can antibodies be used to identify?
the sites of hormone synthesis or target tissue
- polyclonal Ab can be generated against hormones and purified by affinity chromatography
- monoclonal Ab against a single epitope are more specific
What confers hormone action?
Amount/concentration
- measured by immunoassays - RIA, ELISA, FIA, other competitive binding assays
Activity
- Bioassay
Biochemical structure
- chromatography
Advantages of aptamers
- can be chemically synthesized at a low cost with no batch to batch variation
- can be easily modified with different dyes and labels without affecting their affinities
- more chemically stable, have a longer shelf life, can be reversibly denatured without loss of specificity
Assays must show:
- a dose-response relationship
- have sufficient sensitivity, accuracy, precision
- be independent of sample matrix effects
Hormone receptor binding can be measured with
saturation binding assay with Scatchard analysis and the displacement or competition binding assay
Scatchard analysis is used to determine?
- affinity of hormone binding to its receptor
- effective number of receptors present in a cell
peptides can be sequenced by
- Edman degradation
- MALDI-TOF mass spectrometry
- protein sequence can be deduced from cDNA sequence
Peptides can be made by?
- merrifield synthesis using solid phase support
- expressing the proteins in bacteria, eukaryotic cells or in transgenic animals
Endocrine systems can be manipulated by?
- altering endogenous hormone levels
- administering long acting analogues
- affecting the signal transduction process
Advantages of encapsulated cells
- increase efficacy
- reduce potential toxicity
- improve uptake by target tissue
Immune cells can’t get in, but nutrients can
