endocrine System For Appetite Flashcards
Homeostasis
Homeostatic mechanisms act to counteract changes in the internal environment
Variables are regulated so that internal conditions remain stable and relatively constant
Homeostasis is not a steady state but a dynamic equilibrium.
Failure in homeostasis leads to disease
Mechanisms exist at all levels
Cell (e.g. regulation of intracellular Ca2+ concentration)
Tissue (e.g. balance between cell proliferation and cell death (apoptosis)
Organ (e.g. Kidney regulates water and ion concentrations in blood)
Organism (e.g. constant body temperature)
Biological rhythms
Set point of control centre can vary
Circadian (or diurnal) rhythm - “Biological clock” in brain in small group of neurones in suprachiasmatic nucleus
Cues from the environment (Zeitgebers) keep body on a 24 hour cycle.
E.g. Light, Temperature, Social interaction, Exercise and Eating/drinking pattern
Long haul flights crossing time zones can result in mismatch between environmental cues and body clock causing jet lag
Hormone melatonin from pineal gland involved in setting biological clock
Feedback
Negative feedback - response in a way to reverse the direction of change
Most common form of feedback in physiological systems
E.g. hormone release from hypothalamus - TRH, travels in local blood supply to stimulate cells in Ant Pit - TSH - this enters the blood stream towards the target gland - T3 and T4
Short loop feeds back from hormone 2 to the hypothalamus
Long loop feeds back from hormone 3 to the ant pit and to the hypothalamus
Positive feedback - Response in a way so as to change the variable even more in the direction of the change
(Rare, few examples).
Used when rapid change is desirable.
Examples of positive feedback:
Blood clotting - presence of platelets and clotting factors stimualtes the release of more clotting factors
Ovulation
Example of a control system
ADH and body fluid homeostasis
Body water homeostasis - As a % of Lean body mass - Tot body water = 50-60% for males, 45-50% for females
Osmotic pressure of blood plasma monitored by osmoreceptors in hypothalamus
Osmolality vs Osmolarity:
Osmolality = the number of osmoles per Kg of solution - i.e. mass
Osmolarity = the number of osmoles per litre of solution - i.e. volume
Antidiuretic hormone and body fluid homeostasis - If the osmolality increases then the body needs to conserve water - this is detected by osmoreceptros in the hypothalamus, which stimulates the Post Pit to secrete more ADH
This increases reabosption of H2O from urine into the blood in the collecting ducts in the kidney
If the osmolality decreases then the body needs to excrete water, this is detected by osmoreceptors in the hypothalamus, which stimulates the Post Pit to secrete less ADH which decreases reabosption of H2O from the urine into the blood in collecting ducts in the kidney
Plasma glucose homeostasis
After you eat a meal the plasma glucose is going to increase, therefore the pancreas releases insulin
Insulin then stimulates glycogenesis in the liver and also stimulates glucose uptake into tissues (via the GLUT4 receptor)
Therefore the plasma glucose declines/ goes back to normal
If you fast/ dont eat then plasma glucose decreases, this leads to the pancreas releasing glucagon
Glucagon stimulates gluconeogenesis in the liver, so glucose is released into the blood
Therefore plasma glucose increases
The endocrine system
The endocrine system is a collection of glands located throughout the body.
Hormones are chemical signals produced in endocrine glands or tissues that travel in the bloodstream to cause an effect on other tissues
Apart from the endocrine glands, other organs and tissues also release important hormones
Heart (ANP & BNP)
Liver (IGF1)
Stomach (Gastrin, Ghrelin)
Placenta (Inhibin, Placental lactogen)
Adipose (Leptin)
Kidney (Erythropoietin, Renin, Calcitriol)
Mechanisms of communication via hormones
Autocrine - hormone signal acts back on the cell of origin
Paracrine - hormone signal carried to adjacent cells over a short distance via interstitial fluid
Endocrine - hormone signal released into blood and carried to distant target
Neurocrine - hormone originates in neurone and after transport down axon released into bloodstream and carried to distant target cells
The endocrine and nervous systems have several features in common
Both neurons and endocrine cells are capable of secreting
Both neurons and endocrine cells can be depolarised
Some molecules acts as both neurotransmitter and hormone
The mechanism of action requires interaction with specific receptors in the target cells
Both systems work in parallel to control homeostasis
Classification of hormones
Polypeptide
Glycoproteins
Amino acid derivatives
Steroids
Peptide/polypeptide - Largest group Short chains of amino acids. Insulin Glucagon Growth hormone All water soluble
Glycoproteins - Large protein molecules Often made up of subunits Carbohydrate side chain e.g. Luteinizing hormone (LH), Follicle stimulating hormone (FSH), Thyroid stimulating hormone (TSH) All water soluble
Amino acid derivatives (Amines) - Synthesised from aromatic amino acids Adrenaline (tyrosine) Noradrenaline (tyrosine) Thyroid hormones (tyrosine) Melatonin (tryptophan) Adrenal medulla hormones water soluble Thyroid hormones lipid soluble
Steroids - All derived from cholesterol.
Steroidogenic tissues convert cholesterol to different hormones
Cortisol
Aldosterone
Testosterone
All Lipid soluble
Steroid hormones are synthesised from cholesterol
Hormone transport
Some hormones travel in blood in simple solution
Peptides
Adrenaline
Most hormones must bind to (usually) proteins
Often specific proteins
Thyroid hormones (thyroxine-binding globulin, (TBG))
Dynamic equilibrium between bound and free forms of hormone in plasma
Only free form is biologically active
Free hormone + binding protein bound hormone
Roles of carrier protiens - increases solubility of hormone in plasma, increase half life and allows us for a readily accessible reserve
3 main factors that determine hormone levels in the blood
3 main factors determine hormone levels in blood
1) Rate of production:
Synthesis & secretion, the most highly regulated aspect of hormonal control
2) Rate of delivery:
Higher blood flow to a particular organ will deliver more hormone.
3) Rate of degradation:
Hormones are metabolized and excreted from the body
Water soluble hormones (polypeptides (Insulin) glycoproteins (LH) and some amino acid derivatives (Ad/Norad)) bind to cell surface receptors
Binding of hormone to receptor at a GPCR -
Dissociation of G protein α subunit
Activation of effector protein (e.g. adenylyl cyclase)
Formation of second messenger (e.g. cAMP)
Activation of protein kinase (e.g. PKA)
Phosphorylation of target proteins —> Cellular response
Binding of hormone to receptor at a tyrosine kinase domain -
Dimerisation (except insulin receptor which is already dimerised)
Autophosphorylation of specific tyrosines
Recruitment of adapter proteins and signalling complex
Activation of protein kinase (e.g. PKB)
Phosphorylation of target proteins —> Cellular response
Lipid soluble hormones bind to intracellular receptors
Lipid soluble hormones can readily diffuse across the plasma membrane
2 types of receptors
1) cytoplasmic receptor binds to the hormone and receptor hormone complex enters nucleus and binds to DNA
2) Hormone enters nucleus and binds to prebound receptor on DNA e.g. thyroid hormone - binding relieves repression of gene transcription - Receptor binds to specificities DNA sequence called a hormone response element in promotor region of specific genes
Both then lead to expression of new protein mediates effects of hormone
Control of appetite
Appetite control centre (Satiety Centre) is located in the hypothalamus
Hypothalamus contains several clusters of neurones referred to as nuclei
The arcuate nucleus plays a central role in controlling appetite
Other brain areas are also involved
Complex and emerging area.
Neurones of the arcuate nucleus
Neuronal, nutrient & hormonal signals are processed by primary neurones in the arcuate nucleus
Two types of primary neurone:
Stimulatory neurones contain neuropeptide Y (NPY) and Agouti-related peptide (AgRP). These promote hunger
Inhibitory neurones contain pro- opiomelanocortin (POMC) which yields several neurotransmitters including α-MSH and β-endorphin - These promote satiety
Primary neurons synapse with secondary neurones in other regions of hypothalamus and the signals integrated to alter feeding behaviour.
