9.2 - Endocrinology + Endocrine Control Of Appetite Flashcards
What is homeostasis
mechanisms that act to counteract changes in the internal environment
- Dynamic equilibrium
- Variables are regulated so that conditions remain stable and relatively constant
- Failure in homeostasis → disease
- Mechanisms exist at all levels:
☞ cell (ie Ca2+ regulation)
☞ tissue (balance between cell proliferation + apoptosis)
☞ organ (kidney regulating water)
☞ organism (constant body temperature)
Elements of a homeostatic control system
stimulus is a change in environment → receptor detects stimuli → communication via afferent pathway (via nervous system or endocrine system) → control system (ie hypothalamus) determines the set point, analyses afferent input and determines response → communication via efferent pathway → effector causes change ie sweat glands, muscle → negative (or positive) feedback
What are the 3 main roles of the control centre
Ie the hypothalamus
- determine the set point ie core body temp
- analyse the afferent input ie thermoreceptors detecting a rise in core body temp
- determine the appropriate response ie lower core body temp by sweating etc
What are the different types of receptors
- chemoreceptors detect chemical changes eg O2, CO2 and pH levels
- thermoreceptors detect changes in temp
- proprioreceptors detect changes in position and movment (postioning of limbs)
- mechanoreceptors detect mechanical stimuli, such as pressure and stretch
- nociceptors detect potentially dangerous stimuli at the skin, such as temperature and pressure extremes. Ie detects pain
Biological rhythms
- Set point of control centre can change, resulting in biological rhythms
- circadian aka diurnal rhythms
- Human biological clock found in the hypothalamus in the form of a small group of neurones called the suprachiasmatic nucleus
- The biological clock receives input from environmental cues akazeitgeibers (light, temp, physical activity)
- Keep body on 24 hour cycle
-
melatonin hormone is secreted from pineal gland + is involved in setting biological clock
☞ examples of biological rhythms include: cortisol (peaks at 9am) and the menstrual cycle (where levels of different hormones have set points that vary according to a monthly cycle)
Positive + negative feedback
negative
- Opposing direction of change
- Most common form of feedback in physiological systems
- Brings variable back to set point
positive
- Much rarer form of feedback
- Amplifies the stimulus
- This causes variable to deviate even further from set point
- Ie during labour where loop acts to increase strength of each uterine contraction
Osmolarity vs osmolality
osmolarity = the number of osmoles per litre of solution (therefore volume)
osmolality = the number of osmoles per kg of solution (therefore mass)
Osmole = the amount of substance that dissociates in solution to form one mole of osmotically active particles
ie 1mM solution of NaCl ⇢ Na+ + Cl- (therefore osmolarity of 2mOsmol/L (1 from Na+ and 1 from Cl-)
ADH + its role in body fluid homeostasis
high blood osmolality → body needs to conserve more water → detected by osmoreceptors in hypothalamus → thirst (which causes drinking, reducing osmolality) + stimulates posterior pituitary to secrete more ADH → increased reabsorption of H2O from urine into the blood in collecting ducts in the kidney → small volume of concentrated urine → normal blood osmolality
low blood osmolality → body needs to excrete water → detected by osmoreceptors in hypothalamus → posterior pituitary secretes less ADH → decreased reabsorption of H2O from urine into blood in collecting ducts of kidney → large volume of dilute urine → normal blood osmolality
Plasma glucose homeostasis (in broad terms)
in fed state → glucose concentration increases → β cells in islets of Langerhans (pancreas) secrete insulin → stimulates glucose uptake into tissues via GLUT4 + stimulates glycogenesis in liver → plasma glucose declines
in fasted state → decreased plasma glucose → α cells in islets of Langerhans (pancreas) releases glucagon → stimulates glycogenolysis in liver → glucose released into blood → plasma glucose increases
Endocrine system: what are hormones
☞ Chemical signals produced in endocrine glands or tissues that travel in the bloodstream to cause an effect on other tissues
☞ hormones often act on distant target cell
☞ present in the blood at very low concentrations
☞ Has many different methods of communication via hormones ie autocrine, paracrine, endocrine + neurocrine (more detail on separate card)
What are some of the major endocrine glands (and other important organs + tissues)
major endocrine glands
- Hypothalamus
- Pituitary
- Pineal
- Thyroid
- Parathyroid
- Thymus
- Adrenal
- Pancreas
- Ovary / testis
other important organs + tissues
- Heart (ANP + BNP to regulate blood pressure)
- Liver (IGF1 for insulin)
- Stomach (gastrin + ghrelin)
- Placenta (inhibin, placental lactogen)
- Adipose (leptin)
- Kidney (erythropoietin, renin + calcitriol)
Methods of communication via hormones
- autocrine where hormone signal acts back on the cell of origin
- paracrine where hormone signal carried to adjacent cells over a short distance via interstitial fluid
- endocrine where hormone signal is released into blood and carried to distant target cells
- neurocrine where hormone originates in neurone, passed down axon before travelling in bloodstream, and carried to distant target cells
Endocrine + nervous system (similarities + differences)
similarities
- Both neurons + endocrine cells are capable of secreting
- Both cells can be depolarised (ie they are excitable)
- Some molecules act as both neurotransmitter + hormone (ie dopamine)
- The mechanism of action requires interaction with specific receptors in target cells
- Both systems work in parallel to control homeostasis
- Both require receptors
differences
- signal E = hormones, N = neurotransmitters + action potentials
- nature E = chemical, N = chemical + electrical
- transporting E = bloodstream, N = synapses + axons
- speed E = slow, N = fast
Classification of hormones
peptide / polypeptide
- Short chains of AAs
- Ie insulin, glucagon + growth hormone
- All water soluble
glycoproteins
- Large protein molecules with carbohydrate side chain
- Often made up of subunits
- Eg LH, FSH + TSH
- All water soluble
amino acid deriratives (amines)
- Synthesised from aromatic amino acids
- Ie adrenaline, noradrenaline, thyroid hormones (from tyrosine)
- Ie melatonin (from tryptophan)
- Mixture of water (adrenal medulla hormones) and lipid soluble (thyroid hormones)
steroid
- All derived from cholesterol
- Steroidogenic tissues convert cholesterol to different hormones
- Ie cortisol, aldosterone + testosterone
- All lipid soluble
What are the steroid hormones (names)
all derived from cholesterol + are lipid soluble
- Aldosterone
- Testosterone
- Progesterone
- Cortisol
Hormone transport
- Some hormones travel in the blood in simple solution (ie peptides and adrenaline) as they are water soluble
- Lipid soluble hormones are not easily transportable, and therefore need a carrier
- Most hormones bind to (usually) proteins, and these are usually specific (ie thyroid hormones bind to thyroxine-binding globulin)
- Dynamic equilibrium between bound + free forms of the hormone in plasma
- Only the free form is biologically active
What are the main roles of carrier proteins (3)
- Increase solubility of hormone in plasma
- Increase half-life
- Readily accessible reserve
What are the 3 main factors that determine hormone levels in the blood
- rate of production ie synthesis + secretion
- rate of delivery ie higher blood flow to a particular organ will deliver more hormone (ie by vasodilation ⇢ increased blood flow)
- rate of degradation ie hormones are metabolized + excreted from the body
- Note: hormones circulate in the blood at very low concentrations
How do hormones exert their effects? (more detail about specific types of receptor on following cards)
- Endocrine cells synthesise + release hormones into the bloodstream
- Hormone is carried in the bloodstream to distant target tissues
- Target cells have to express a specific receptor for the hormone in order to carry out the specific cellular response to the hormone
- water soluble hormones bind to cell surface receptor (as they can’t get inside the cell as not lipid soluble)
- lipid soluble hormones bind to intracellular receptors (as they can get in the cell via diffusion)
Receptors for water soluble hormones + mechanisms of action
- these are cell surface receptors (as can’t get inside cell as not lipid soluble, but still need to have receptor in order to relay information to inside of cell)
- two types of receptor: tyrosine kinase (ie insulin receptor) or G protein coupled receptor (ie adrenaline receptor)
G protein coupled receptor
Hormone binds to receptor → dissociation of G protein α subunit → activation of effector protein (eg adenylyl cyclase) → formation of second messenger (eg cAMP) → activation of protein kinase (eg PKA) → phosphorylation of target proteins → cellular reponse
tyrosine kinase receptor
Hormone binds to receptor → dimerisation → autophosphorylation of specific tyrosines → recruitment of adapter proteins and signalling complex → activation of protein kinase (eg PKB) → phosphorylation of target proteins → cellular response
Receptors for lipid soluble hormones + mechansims of action
- these are intracellular receptors
- lipid soluble can get in cell via diffusion
- act by modulating gene transcription
- once in cell there are two types:
type 1 = cytoplasmic receptor binds hormone + receptor-hormone complex enters nucleus + binds to DNA
type 2 = hormone enters nucleus + binds to pre-bound receptor on DNA. Binding relieves repression, and allows gene transcription to take place
Hormone enters cell → binds to type 1 or 2 receptor → receptor binds/ bound to specific DNA sequence called hormone response element (HRE) in promoter region of specific genes → gene transcription is stimulated (so mRNA, and new protein formed) → expression of new protein mediates the effects of hormone → cellular response
Do lipid soluble or water soluble hormones work quicker + why?
- Water soluble work quicker
- water: is just triggering intracellular pathways that already exist
- lipid: need to wait for gene transcription + translation to occur before effect in place
Control of appetite
- Appetite control centre aka satiety centre is located in hypothalamus
- Hypothalamus contains several clusters of neurones = nuclei
- arcuate nucleus = plays central role in controlling appetite (in detail in different card) but neuronal, nutrient + hormonal signals are all process by primary neurones here
- Other brain areas are also involved
Why is arcuate nucleus located very near capillaries?
- It is located in the hypothalamus
- Plays central role in controlling appetite
- Near capillaries so can sense substances in blood
Neurones of the arcuate nucleus
- Hormonal and nutrient signals from blood are processed by primary neurones here
- Two types of primary neurone (stimulatory + inhibitory)
- Primary neurones synapse with secondary neurones in other regions in hypothalamus
- Signals are integrated in order to alter feeding behaviour
stimulatory primary neurones
- Contain neuropeptide Y (NPY)
- Contain Agouti-related peptide (AgRP)
- These both promote hunger: orexigenic
inhibitory primary neurones
- Contain pro-opiomelanocortin (POMC) which yields several neurotransmitters (including α-MSH and β-endorphin). α-MSH acts at MC4 receptors
- These promote satiety: anorexigenic
Hormonal signals from gut → hypothalamus
ghrelin
- Peptide hormone released from stomach wall when empty
- Stimulates the excitory primary neurones in arcuate nucleus
- Therefore stimulates appetite
- Filling of stomach inhibits ghrelin release
PYY (peptide tyrosine tyrosine)
- Short peptide hormone released by cells in ileum and colon in response to feeding
- Inhibits the excitory primary neurones of the arcuate nucleus
- Stimulates the inhibitory neurons
- Effect therefore supresses appetite
- Note: in obese individuals, PYY response in blunted following food intake
Hormonal signals from body → hypothalamus
leptin
- Peptide hormone released into blood by adipocytes
- Stimulates inhibitory neurones, and inhibits the excitory neurones in arcuate nucleus
- Overall effect = supress appetite
- Also induces expression of uncoupling proteins in mitochondria, therefore energy is dissipated as heat
- Patients can have defective leptin → become obese
insulin
- Supress appetite by similar mechanism as leptin
- Leptin seems to be more important in this process
amylin
- Peptide hormone secreted by β cells in pancreas
- Roles aren’t fully understood
- Known to supress appetite, decrease glucagon secretion and slow gastric emptying
- Amylin analogues can be used to supress appetite synthetically (ie pramlintide)
Effect of leptin resistance
- Obesity
- Leptin gene can have loss of function due to mutations (this is rare)
- These patients respond well to leptin injections, bringing them back down to lower weights
Effect of leptin resistance
- Obesity
- Leptin gene can have loss of function due to mutations (this is rare)
- These patients respond well to leptin injections, bringing them back down to lower weights
