Physiology Flashcards
Mechanisms of hormone release
- humoral - respond to changing levels of ions or nutrients in the blood
- Neural - stimulation by nerves
- Hormonal - stimulation received from other hormones
Components of an endocrine axis
- Detection of homeostatic imbalance
- Ligand-Receptor activates secretory apparatus
- Release of hormone from cell
- Hormone in extracellular fluid – blood transport
- Target organ recognition of hormone - receptor
- End organ response to hormone
- Detector sense return to homeostasis – negative feedback
- Hormone cleared
- Synthesis of hormone reserves
3 types of hormones
- Hydrophilic = protein/peptide hormones
- Really small/variable = tyrosine derived hormones
- Hydrophobic = steroid hormones
Storage, release and inactivation of protein/peptide hormones
Storage: secretory granules or vesicles
Release/action: Hydrophilic bind cell surface receptors and activate intracellular signalling pathways
Rapid acting and short lived
Inactivation: internalised by receptor mediated endocytosis, sequestered by kidney –> excreted
Steroid hormones and inactivation
Lipids: derived from cholesterol. Include: cortisol, aldosterone, testosterone and progesterone.
Lipophilic:
- Require transport proteins - Bind intracellular receptors
Inactivation (Liver)
1. Cytochrome P450 oxidase 2. Conjugated
3. Excretion in bile
Examples of tyrosine-derived hormones and which bind extracellular and nuclear receptors
Catecholamines - adrenaline, and NA (extracellular)
Thyroid hormones - thyroxine (nuclear)
Dopamine (extracellular)
What determines how sensitive a receptor is to a hormone?
- number of receptors
- affinity of the receptor
- downstream signalling molecules
Capacity for maximal response is determined mainly by the number of functional cells
Overload desensitisation
Prolonged exposure to stimulus decreases cells response to the level of exposure.
Allows receptors to respond to changes in concentration of a signal rather than absolute concentration.
Biggest endocrine organ?
Most important endocrine organ?
Biggest - gut
Important - H-P-x axis
Hormones produced in the anterior pituitary
GH ACTH TSH LH PRL FSH
Hormones stored in the posterior pituitary
Oxytocin and vasopressin
Regulation of ACTH release
• Stimulation of release • CRH and ADH (hypothal.)
• Stress
• Hypoglycemia
• Circadian pattern of
release
• Highest levels early AM • Sleep-wake cycle (jet-
lag)
What is produced from pre-pro-opiomelanocortin?
- ACTH
- Endorphin
- Lipotrophin
- Melanocyte-stimulating hormone
Action of ACTH
• ACTH stimulates secretion of adrenal glucocorticoids
• Binds cell-surface melanocortin type II receptors (MC2R) • GPCR adenylyl cyclase cAMP protein kinase A
• Most dense in the zona fasciculata
• Regulates steroid hormone secretion (2 ways)
1. RAPID = stimulate lipoprotein uptake into cortical cells, cholesterol delivery
2. LONG TERM = stimulate transcription of steroidogenic enzyme genes
Adrenal gland hormones produced
Adrenal medulla - catecholamines
Zona reticularis - sex hormones
Zona fasciculata - glucocorticoids (cortisol)
Zona glomerulosa - mineralocorticoids (aldosterone)
**corticosteroids = glucocorticoids and mineralocorticoids
What mediates secretion of mineralocorticoids (aldosterone)?
- produced in zone glomerulosa
- mediated by mostly angiotensin II, and local increase in [K+]
Action of aldosterone in the kidney
- ↑ active K+, H+ secretion
- ↑ Na+/K+-ATPase
- active Na+ reabsorption (water follows) • ↑ increases of BP and blood volume
Action of glucocorticoids
- CHO metabolism – elevates blood [glucose]
- Stimulate gluconeogenesis (mobilises AAs, ↑ conversion anzymes) • ↓ cellular glucose use (oxidation of NADH)
- Lipid metabolism – elevates blood [fat] • Mobilises FAs from adipose tissue
- Also stimulates b-oxidation energy
- Protein metabolism – elevates blood [Protein, AA]
- Mobilises AAs from non-hepatic tissues (enhances liver protein synthesis)
- Anti-inflammatory
- Blocks early stage inflammatory inception
- Increases healing of inflammation
- Suppresses cellular immune response, stabilises lysosomes, reduces vessel permeability.
Production of cortical sex hormones
- Synthesised in the zona reticularis
- DHEA (dehydroepiandrosterone)
- Androstenedione
- Converted in peripheral tissues to testosterone, oestrogen
Secretions of the pancreatic islet of Langerhan cells
α-cells: secrete glucagon
β-cells: secrete insulin (+ amylin) ∆-cells: secrete somatostatin
Precursor thyroid hormone
Thyroglobulin
Thyroid hormones and what they are derived from
Derived from tyrosine
- thyroxine T4 (usually transformed into T3 within target cells, because T4 has low biological activity) - main one secreted and circulated in bloodstream
- Triiodothyronine T3 - binds to receptors, and has more biological potency than T4
2 major components of thyroid hormone synthesis
- Iodine
2. Thyroglobulin precursor
Function of iodine in thyroid hormone synthesis
Thyroidhormonesneedlargeamountsofiodine(I2). Scarce, low levels absorbed. (DRI 1mg/week)
Iodine is absorbed as iodide (I-) and converted to iodine.
Thyroidglandshavepowerfuliodidepumpstoconcentrateiodine
within the thyroid gland. ([I-] in follicular cells 20-50x > plasma)