Endo physiology L intro 2022 Flashcards
Learning Objective
Be able to understand the consequences of common endocrinological diseases
Be able to understand the effects of hormones on multiple organ systems within the body to achieve growth, reproduction and maintain homeostasis (energy and mineral metabolism).
Neuroendocrine integration
The endocrine and nervous systems may share the same signalling molecules and are integrated in their control of physiological processes.
paracrine secretion
Neurotransmitter secretion
Hormonal secretion
Neurohormone secretion
Hormonal control of physiological functions
Energy metabolism:
Mineral metabolism:
Growth
Reproduction
Energy metabolism:
hormones
insulin, glucagon, cortisol, adrenaline, thyroid hormone and growth hormone.
Mineral metabolism:
parathyroid hormone, calcitonin, Vitamin D, angiotensin, renin and aldosterone.
Growth:
growth hormone, thyroid hormone, insulin, oestrogen and androgens and a large number of growth factors.
Reproduction:
oestrogen, androgens, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), prolactin and oxytocin.
Reproduction:
oestrogen, androgens, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), prolactin and oxytocin.
why aren’t hormones simple?
Fertility linked to BCS (body condition score)
So fertility also impacted by energy metabolism and partitioning of nutrients
Genetic selection for increased production (eg milk yield) will favour animals that partition nutrients to production may be at cost of BCS, decreasing fertility
Related to complex interplay of many hormones in the body, nutritional status, production status, welfare, etc
So what do hormones do??? Proteins….
Proteins can be structural, receptors, messengers, transporters etc.
Different proteins play different roles.
Hormones influence their production
Concept 1: Amplification of signal
Eg. One chemical messenger receptor on a target cell increased enzyme function
Increased production of multiple mRNA molecules to form enzymes, or
Production of cAMP which can also activate enzymes.
In such a way, very low levels of hormones (ng/100ml) in the blood stream can cause significant biological effects in cells which may be prolonged, lasting minutes to days.
Concept 2: Lipophilic versus Hydrophilic hormones (4)
Chemical structure Steroid hormones -> lipophilic Protein hormones -> hydrophilic Tyrosine hormones -> thyroid hormones lipophilic/amphipathic Fatty acid hormones -> lipophilic
Consider the properties that being lipophilic or hydrophilic conveys to a hormone
Concept 3: Hormone synthesis and storage A. Amino acid hormone synthesis
Protein and polypeptide hormones Preprohormones cleaved in the RER to form prohormones modified by Golgi to form active hormone Most of hormone produced is stored in granules before being released by exocytosis Exocytosis triggered by ATP and Ca++
B. Steroid hormone synthesis
Synthesised from triglycerides and cholesterol (synthesised by the liver) -> lipid soluble
TG or Cholesterol may be stored in the endocrine cell (lipid droplets) but steroid hormones are released as they are synthesised
Production controlled by production of enzymes in pathways
The formation of pregnenolone from cholesterol is the first step in formation, however final hormone produced depends on the enzymes produced by that cell type
Concept 4. The transport of hormones in the blood - proteins
hydrophilic
carried in plasma in dissolved form
May travel as multiple, single or as subunits of the biologically active molecule
May have binding proteins that affect their half-life or activity
Concept 4. The transport of hormones in the blood- steroids and thyroid hormones
Lipophilic
carried in plasma in association with both specific and nonspecific binding proteins
amount of unbound, active hormone relatively small
Concept 5: Plasma membrane receptors
Protein hormones have specific receptors on target cells plasma membranes
Hydrophilic – wont cross PM unaided
Formation of reversible noncovalent bonds
Hormone-receptor complex may be degraded internally by the cell
Available receptor concentration may change
Due to other hormones
Due to agonist with greater affinity
Due to pathological elevation of hormone
Concept 6: Postreceptor cell responses
Steroids act directly with the cell nucleus through the formation of a complex with its cytosolic receptor
Results in mRNA being produced
Protein hormones need a second messenger as they cannot enter the cell (hydrophilic)
Best known is cAMP which is formed from the activation of adenyl cyclase by the hormone-receptor complex.
cAMP can then phosphorylate protein kinases which are responsible for biological actions
Hydrophilic hormone action on target cells .
Eg. TSH, adrenaline.
Act on membrane receptor as cannot diffuse through cell membrane
Lipophilic hormone action on target cells.
Eg. Oestradiol.
Act on specific receptors within the cytoplasm or nucleus after diffusing through cell membrane.
Concept 7: Metabolism of hormones
Steroid hormones are metabolised by conjugation with sulphates and glucuronides, which makes them water soluble.
Largely done in liver
Thyroid hormones are de-iodinised during metabolism
Protein hormones are cleaved by peptidases
Metabolites are generally less biologically active but not always
Dihydrotestosterone more potent than testosterone
Oestrone, metabolite produced from adipose tissue is more potent than its precursor oestradiol-17β
Concept 8: Rate of hormone clearance
Generally, rate of synthesis reflects rate of clearance
Exceptions occur, eg:
Decrease clearance during pregnancy as a result of increased hormone-binding proteins
Increase clearance due to liver disease as a result of decreased hormone-binding proteins
Concept 9: Feedback control mechanisms
The most important feedback control for hormones is the negative feedback system in which increased hormone concentrations result in less production of the hormone, usually through an interaction with the hypothalamus or pituitary gland
Allows for maintenance of optimal hormone concentrations
Concept 10: Influence of pineal gland
Endocrine secretary patterns can be influenced by factors such as sleep or light, and can produce diurnal patterns (circadian rhythms) or seasonal patterns.
Through the action of the pineal gland which receives neural input regarding light
day/night patterns.
Increasing day length -> seasonal patterns
Endocrine diseases
Too little or too much hormone activity
endocrine diseases too fillet hormone activity
Hyposecretion
Increased clearance
Tissue resistance
Too much hormone activity
Hypersecretion
Reduced plasma protein binding
Reduced clearance
Excessive response at target tissue
Compare and contrast the general concepts of amino acid based hormones to fatty acid and cholesterol based hormones
