endocrine System For Appetite Flashcards

1
Q

Homeostasis

A

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)

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2
Q

Biological rhythms

A

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

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3
Q

Feedback

A

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

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4
Q

Example of a control system

ADH and body fluid homeostasis

A

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

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5
Q

Plasma glucose homeostasis

A

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

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6
Q

The endocrine system

A

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)

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7
Q

Mechanisms of communication via hormones

A

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

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8
Q

The endocrine and nervous systems have several features in common

A

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

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9
Q

Classification of hormones

Polypeptide

Glycoproteins

Amino acid derivatives

Steroids

A
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

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10
Q

Hormone transport

A

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

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11
Q

3 main factors that determine hormone levels in the blood

A

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

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12
Q

Water soluble hormones (polypeptides (Insulin) glycoproteins (LH) and some amino acid derivatives (Ad/Norad)) bind to cell surface receptors

A

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

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13
Q

Lipid soluble hormones bind to intracellular receptors

A

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

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14
Q

Control of appetite

A

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.

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15
Q

Neurones of the arcuate nucleus

A

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.

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16
Q

Hormonal signals from the gut to the hypothalamus

A

Ghrelin - Peptide hormone released from stomach wall when empty - Stimulates the excitatory primary neurones in arcuate nucleus & therefore stimulates appetite
Filling of stomach inhibits ghrelin release

PYY (peptide tyrosine tyrosine) - Short (36-amino acid) peptide hormone released by cells in the ileum and colon in response to feeding

Inhibits the excitatory primary neurones of the acrcuate nucleus and stimulates the inhibitory neurones. Effect is therefore to suppress appetite
Injection of PYY into mouse brain makes them anorexic
Blunted PYY response following food intake in obese humans

17
Q

Hormonal signals from the body to hypothalamus

A

Leptin - Peptide hormone released into blood by fat cells (adipocytes)
Has 2 effects in the arcuate nucleus
1) stimulates the inhibitory (POMC) neurones
2) inhibits the excitatory (AgRP/NPY) neurones in arcuate nucleus
Overall effect is therfore to suppress appetite

Leptin induces expression of uncoupling protiens in mitochondria
Energy therefore dissipates as heat

Insulin - Suppresses appetite by similar mechanism as leptin
Seems to be less important than leptin in this respect

Amylin - Peptide hormone also secreted by ß cells in the

18
Q

Leptin

A

Discovered in 1994 by Jeffrey Friedman who studied an inbred strain of obese mouse (ob/ob)

Used positional cloning to show ob/ob mice have loss of function mutation in leptin gene.

Similar loss of function leptin gene mutations have also been discovered in humans (although incredibly rare)

These patients respond remarkably to leptin injection

Little effect of leptin however if administered to “common obesity” patients (“leptin resistance”)