Intercellular Communication Flashcards
What is the endocrine system?
- A blood-borne, long distance biochemical communication system
- Aims to control and regulate a huge number of physiological processes = maintain homeostasis
Exocrine
External secretion (saliva, sweat…)
Endocrine
Internal secretion = blood
Endocrine organs
- Pituitary gland
- Pineal gland
- Thyroid gland
- Parathyroid glands
- Adrenal glands (cortex and medulla)
Endocrine cells
- Pancreas
- Thymus
- Gonads
- Hypothalamus
What is an endocrine gland?
Ductless glands, comprised of endocrine cells - these glands secrete hormones directly into the blood
Are endocrine hormones long or short distance messengers?
Long distance
Acting on target cells - endocrine
Endocrine hormones act on target cells that contain specific receptors for a particular hormone
Target cells - receptors
Receptors are selective for the specific molecules that bind to them
- If there is no receptor binding, then no physiological effect results = antagonism
Where are receptors found in?
- Surface (plasma membrane)
- Cytoplasm
- Nucleus
What is cortisol?
As your body perceives stress, your adrenal glands make and release the hormone cortisol into your bloodstream. Often called the “stress hormone,” cortisol causes an increase in your heart rate and blood pressure. It’s your natural “flight or fight”
Function of hormones:
- fetal development
- cell growth and cancer
- metabolism
- cardiovascular function
- renal function
- skeletal function
- reproductive function
- immune function
- CNS function
- maintain homeostasis
What is homeostasis?
Homeostasis refers to an organism’s ability to regulate various physiological processes to keep internal states steady and balanced
Example of negative feedback homeostasis
Body temp exceeds 37C —> nerve cells in skin and brain —> temp regulatory center in brain —> sweat glands throughout the body
Order if negative feedback -
- Stimulus
- Sensor
- Control
- Effector
What is negative feedback loop?
It is responsible for reversing the stimulus by activating the opposite responses. Thus, the productivity of the stimulus is reduced. This type of feedback mechanism stabilizes biological systems maintained under homeostatic conditions, important for a constant internal environment
Examples of negative feedback
Regulation of body temperature, blood pH, hormone levels, the oxygen/carbon dioxide balance, blood sugar levels, blood pressure, acid/base balance, water balance (osmoregulation), calcium levels, and energy balance
What is positive feedback loop
Positive feedback homeostasis is a type of feedback mechanism in biological systems, reinforcing a particular stimulus in the body. Therefore, this type of feedback mechanism promotes the change to proceed further. Thus, the initial change amplifies until the removal of the stimulus
ESSENTIALLY PUSHING THE BODY OUT OF HOMEOSTATIC STATUS
Positive feedback - childbirth
Childbirth is one of the most precise examples of positive feedback mechanisms. During childbirth, the pressure on the cervix due to the pushing of the child’s head downwards induces the release of oxytocin, which in turn stimulates further contractions of the cervix. Subsequently, these contractions stimulate the release of oxytocin until the baby is born
Examples of positive feedback
- Lactation = Breastfeeding stimulates milk production, which causes further feeding. And, this continues until the baby stops feeding.
- Ovulation = The dominant follicle inside the ovary releases estrogen, which stimulates the release of FSH and LH. These hormones stimulate further growth of the follicle.
- Blood clotting = The release of clotting factors by the activated platelets stimulates the aggregation of more platelets at the site of injury.
- Fruit ripening = The ripened fruits release ethylene, which stimulates the ripening of the nearby fruits
Is childbirth homeostasis?
No
Hormone classification
- Steroid hormones
- Peptide hormones
- Amino acid derivatives
Steroid hormones
- Derived from cholesterol steroid ring structure
- Produced by the gonads, the adrenal cortex and the kidneys
- Cannot be stored in the vesicles in the endocrine cells that produce them
- Receptors are located inside target cell
Peptide hormones
- Comprised of chains of amino acids
- Can be stored in vesicles in endocrine cells
- Do not readily pass through cell membranes
- Water soluble
- Receptors are found on the cell surface of their target organs
Amino acid derivatives
Tyrosine derivatives Catecholamines: - epinephrine (adrenaline) - norepinephrine (noradrenaline) - dopamine Thyroid hormone: - T4 (thyroxine) - T3 (triidothyroine)
Tryptophan derivatives:
- melatonin
- serotonin
What do steroid hormones and thyroid hormones bind to?
Intracellular receptors, whilst all other hormones bind to extracellular
Mechanisms of hormone release
- Humoral
- Neural
- Hormonal (axis)
Humoral hormone release
Stimulation from changing levels of ions or nutrients in the blood
- parathyroid hormone (PTH)
- PTH controls calcium homeostasis, responds to Ca2+ changes
Neural hormone release
Stimulation by nerves
- the nervous system directly controls the release of the hormone
- sympathetic stimulation (presynaptic) –> chromaffin cells adrenal gland (postsynaptic) –> epinephrine/norepinephrine (neurohormone)
Hormonal hormone release
Stimulation from other hormones
- a hormone controls the release of a different hormone
Neurotransmitters
Released into the blood, secreted by chromaffin cells (neuroendocrine cells found in the medulla of the adrenal glands)
Hormones produced by neurons
Oxytocin and vasopressin, produced in the hypophysis (hypothalamus) - secreted by the posterior pituitary
Releasing hormones
Produced by neurons that will stimulate a gland instead a target organ
- They are transported along neural axons stored and released into the hypophyseal portal system. They then rapidly reach the anterior pituitary where they exert their hormonal action
Why can a steroid hormone not be stored in a vesicle?
Because they are lipophilic, they cannot be stored in vesicles from which they would diffuse easily and are therefore synthesized when needed as precursors
How do negative feedback mechanisms control hormone secretion?
In negative feedback systems, a stimulus elicits the release of a substance; once the substance reaches a certain level, it sends a signal that stops further release of the substance
The pituitary gland
- a pea sized gland
- sits in a bony hollow base of the skull (sella turcica), underneath the brain and behind of the nose
- also known as the hypophysis
Processes of the pituitary gland
Sometimes called the ‘master’ gland’, controls many different processes:
- Blood pressure
- Sexual maturation and reproduction
- Metabolism
- Growth…
Structure of the pituitary gland (hypophysis)
- Anterior pituitary = adenopophysis
2. Posterior pituitary = neuropophysis
Posterior hypophysis position
Attached to the and innervated by the hypothalamus, which controls its activity. The attachment is the stalk or infundibulum
Anterior hypophysis
Synthesises and secretes hormones, non-nerve origin. Under the control by hormones released by the hypothalamus
Hypophysis portal system
Carries blood from the hypothalamus to the anterior pituitary and between the two sides - composed of six distinctive types of secretory cells (one for each hormone)
Posterior hypophysis
Stores and secretes, but does not synthesise hormones, nervous tissue origin. Peptide hormones are synthesised in the cell bodies of hypothalamic neurons - taken to the terminal and stored.
The hormones are released at the terminal into the bloodstream
Hypothalamus
- Works with the pituitary = main regulators of the endocrine system
- Receives input from the cortex, thalamus and limbic system
Hypophysis vasculature
Carries hormones from the hypothalamus to the anterior pituitary :
- hypothalamus secretes releasing hormones
- controls secretion of anterior pituitary hormones
Carries hormones out of the pituitary:
- anterior = endocrine cells
- posterior = from hypothalamus
Pituitary gland - hormones
The pituitary secrets 8 hormones Anterior: - TSH = thyroid stimulating hormone - ACTH = adrenocorticotropic hormone - FSH = follicle stimulating hormone - LH = luteinizing hormone - GH = growth hormone - PRL = prolactin
Posterior:
- ADH = anti-diuretic hormone (vasopressin)
- Oxytocin
ACTH - Adrenocorticotrophic hormone
- stimulates the adrenal gland to release corticosteroids
- important for responding to stress
TSH - Thyroid stimulating hormone
- stimulates the thyroid to release hormones
- thyroid hormones involved in regulating metabolism
FSH - Follicle stimulating hormone
- stimulates follicle growth and oestrogen production from ovary
- sperm production
LH - Luteinizing hormone
- plays role in ovulation
- stimulates androgen (males) secretion by the testis
GH - Growth hormone
- growth and puberty
- stimulates protein synthesis = cell production
- levels decrease throughout lifespan
PRL - Prolactin
- breast development and milk production
- normally levels are low until pregnancy
- found in males as well as females
ADH - Anti-diuretic hormone
- water retention and vessel constriction
Oxytocin hormone
- uterus contraction during childbirth
- stimulates breast milk production
- social bonding = ‘love hormone’
Pituitary gland - end organ
Several hypothalamic pituitary axes Target: the 'end organ' - the organ at which the hormone targets = home of target cells - express specific receptors - specific response to the hormone
Non-endocrine end organs
- Breasts
- Bone
- Kidneys
Other endocrine end glands
- Thyroid gland
- Adrenal gland
- Liver
- Gonads
Pituitary gland - regulation
Hypothalamus releases:
- Releasing hormones (RH) stimulates the synthesis of hormones at the anterior pituitary
- Inhibiting hormones (IH) prevent the synthesis and secretion of hormones from the anterior pituitary
Acromegaly
- excess GH in adults (tumur or dysfunction) - after growth plate fusion
Acromegaly is a hormonal disorder that develops when your pituitary gland produces too much growth hormone during adulthood
Gigantism
- excess GH in young in children or adolescents (tumur or dysfunction) - prior to growth plate fusion
- increased height
Pituitary dwarfism
- occurs due to a lack of hGH (growth hormone deficiency)
- normal body proportions
- children with GHD have abnormally short stature with normal body proportions. GHD can be present at birth (congenital) or develop later (acquired)
- can be treated with hGH
Diabetes insipidus
- too much vasopressin (ADH)
An uncommon disorder that causes an imbalance of fluids in the body. This imbalance leads you to produce large amounts of urine. It also makes you very thirsty even if you have something to drink
Cushing’s syndrome
- hyper secretion of ACTH/cortisol (‘stress hormone’)
- lipid reservers mobilized, adipose tissue accumulates on cheeks and neck
Thyroid
- in the neck anterior to the trachea inferior to larynx
- two lateral lobes and an isthmus
- produces two types of hormones
> Thyroid hormone = T4 (thyroxine) and T3 (triiodothyronine)
> Calcitonin = involved with calcium and phosphorus metabolism
T3
- responsible for most of the biological activities of the thyroid hormones
- thyroid key regulator of metabolism
- T3 deficiency produces hypothyroidism (even in the presence of normal T4 levels)
T4
- much more T4 is produced, but T3 is more potent
- binding selectivity: nuclear receptors for thyroid hormones prefer T3 to T4
- T4 is a prohormone
What is a prohormone
The body naturally produces prohormones as a way to regulate hormone expression, making them an optimal storage and transportation unit for inactive hormones
Prohormone
- is a precursor hormone
- minimal hormonal effect by itself
- circulates in the bloodstream as a hormone in an inactive form
- ‘switched on’ by post-translational modification
- T4 to T3 conversion (enzymatic) takes place in the target cell
- T3 = ‘ready to use’
= T4 needs to be converted
The TH storage issue
- thyroid can build a 6 month supply of hormones
- but = stability is a problem
- T3 = half life is very short
- T4 is 5-7 times more stable
- synthesis of the hormones on demand requires iodide, which not always available
Proteolysis release t3 and t4 from larger molecule
The TH storage issue: 2
- t3 and t4 are very hydrophobic
- their storage is very difficult
- the solution: to synthesise t3 and t4 from a larger protein (thyroglobulin)
Actions of T3 and T4
Direct and indirect effects:
- increase basal metabolic rate
- increase in oxygen consumption
- lipid synthesis and lipolysis
The effects of calcitonin on the thyroid gland
- secreted from thyroid when blood Ca2+ levels are high
- low Ca2+ inhibits secretion
Calcitonin lowers Ca2+ by:
- slowing the calcium releasing activity of osteoclasts in bone
- increased Ca2+ excretion by the kidney
Graves’ disease
- auto immune condition = antibodies against TSH receptor
- to stimulate the thyroid gland
- to produce and release thyroid hormones (t3 and t4)
Cellular changes in the gland:
- follicular cells increase in (hypertrophy)
- and in number (hyperplasia)
- Causes goitre, eye bulging (exophthalmos)
Goitre
enlarged thyroid
What glands are responsible of managing calcitonin?
Thyroid and parathyroid
Parathyroid glands
- most people have four
- On posterior surface of thyroid gland
Types of cells found in the parathyroid glands
- chief cells = produce parathyroid hormone (peptide hormone)
- Oxyphil cells = unknown function
Function of parathyroid glands
- opposite effect to calcitonin
- increase in blood Ca2+ conc when it gets too low
Mechanism of raising blood calcium:
1. stimulating osteoclasts to release more Ca2+ from bone
2. decreasing excretion of Ca2+ by kidney
3. Activates vitamin D, which stimulates the uptake Ca2+ from the intestine
Adrenal gland - structure
- also known as suprarenal (‘suprarenal’ means on top of the kidney)
- each is really two endocrine glands
- adrenal cortex (outer, several layers - vary by species
- adrenal medulla (inner)
Adrenal gland Cortex - hormones
- secrets lipid-based steroid hormones, called ‘corticosteroids’
- Mineralocorticoids = aldosterone
- Glucocorticoids = cortisol
Adrenal gland Medulla - hormones
- adrenal medulla secrets epinephrine and norepinephrine (‘fight or flight’), produced by chromaffin cells (modified neurons)
Aldosterone
- the main mineralocorticoid
- response to a decline in either blood volume or blood pressure (eg. severe hemorrhage)
- prompts distal and collecting tubules in kidney to reabsorb more sodium
- water flows by osmosis
- blood volume and pressure thus increase = less aldosterone released - homeostatic loop
Cortisol
- the most important glucocorticoid
- helps the body deal with stressful situations within minutes
- physical = trauma, surgery, exercise
- psychological = anxiety, depression
- physiological = fasting, hypoglycemia, fever, infection
- regulates a variety of important cardiovascular, metabolic, immunologic and homeostatic functions including water balance
Further cortisol functions
- keeps blood glucose levels high to support brain’s activity
- glycogen breakdown, gluconeogenesis
- forces other body cells to switch to fats and amino acids as energy sources
- catabolic steroid: break down of proteins etc
- redirects circulating lymphocytes to lymphoid and peripheral tissues (where pathogens usually are)
- in large intestines, depresses immune and inflammatory responses = therapeutic use
Hormonal stimulation of glucocorticoids
- stress activates hypothalamus
- hypothalamus releases CTH into ant. pituitary
- anterior pituitary releases ACTH on adrenal gland
- adrenal gland releases glucocorticoids eg. cortisol
- cortisol inhibits ACTH and CTH release
= homeostatic loop
Addison’s disease
- hyposecretion by adrenal cortex
- low cortisol and aldosterone = low blood glucose and sodium
- dehydration , fatigue, loss of appetite, abdominal pain
HPG axis
- hypothalamic pituitary gonadal axis
- gonads = testes and ovaries
- begins with gonadotropin releasing hormone
- gonads release sex steroid hormones
Where are steroid hormones produced?
- gonads
- adrenal cortex
- kidneys
Sex hormones
- cholesterol
- progesterone and oestrogen
- androgens
- glucocorticoids
- mineralocorticoids
Androgens
- testosterone and dihydrotestosterone (DHT)
- Effect = stimulate spermatogenesis (sperm production), development of secondary sexual characteristics
- the precursor of all estrogens (oestrogens)
Estrogen and progesterone
Estogens
- estrine, estradiol, estriol, estetrol
- like testosterone, have anabolic effects
Effect
- stimulate ovulation
- with progesterone, regulate the menstrual cysle
- sperm production
- the development of sexual secondary characteristics
Brain to the gonads
- GnRH from hypothalamus
- release of LH/FSH from pituitary
- release of sex steroid hormones from gonads
- effect on gonads, inhibit pituitary and hypothalamus
- homeostatic loop
- rise in GnRH, rise in steroid, then decrease in GnRH
Puberty
- not an isolated event
- it is a process which takes place over several years
Through puberty: - rise in GnRH - rise in LH/FSH - rise in sex hormones but steroids (mostly) inhibit production of GnRH and LH/FSH
‘Gonadostat hypothesis’
- initially less gonadal steroid, but strong inhibition
- at puberty hypothalamic sensitivity to gonadal steroid inhibition starts to decrease
- rise in GnRH , LH/FSH and gonadal steroids
Pancreas
- not an endocrine organ it has both exocrine and endocrine cells
- acinar cells (forming most of the pancreas) = exocrine cells
- islet cells (of Langehans) = endocrine cells
Cells that form most of the pancreas
Acinar cells
- exocrine function
- secrete digestive enzymes
Pancreatic islet endocrine cells
- alpha cells = secrete glucagon, raises blood sugar
- beta cells = secrete insulin, lowers blood sugar
- rare delta cells = secrete somatostatin inhibits glucagon
Reactive homeostasis
- Calcitronin
calcium levels release hormone to manage calcium levels
Predictive homeostasis
- Insulin
consumption of a meal can trigger insulin before blood glucose rises
Type 1 diabetes
- autoimmune, beta cell loss
Type 2 diabetes
- insulin insensitivity (sometimes poor diet)
Pineal gland
- another pea sized gland
- shaped like a pine cone
- secretes melatonin
- role in sleep patterns
Melatonin
- not melanin
- produced from serotonin
- production = stimulated by darkness, inhibited by light
Pineal gland - hormones
- receives inout from the retina
- melatonin increases as light decreases
- cortisol rhythm (wakefulness) follows the melatonin rhythm
Pineal gland - dysfunction
- insomnia/ sleep cycle disturbance
- pineal tumor = block in cerebral aqueduct
Endocrine cells in the heart
- atrial natriuretic peptide (ANP)
- stimulates kidney to excrete more salt
- decrease in excess blood volume and high blood sodium concentration
Endocrine cells in the placenta
- estrogens, progesterone
- hCG (human chorionic gonadotropin = Gr. Khorion - membrane enclosing the fetus
Endocrine cells in the kidneys
- juxtaglomerular cells secrete renin
- renin, angiotensin –> adrenal cortex –> aldosterone
Endocrine cells in the skin
- modified cholesterol with UV exposure becomes vitamin D3 precursor
- vitamin D3 necessary for Ca2+ metabolism = signals intestine to absorb Ca2+
Is breathing homeostatic?
Yes - body detects O2 levels, but high CO2 is big driver of increased breathing
Autonomic effects on cardiac function
- SNS = increase heart rate and force
- PNS = decrease heart rate and equal force
ANS - alpha
receptor activation causes contraction and secretion
ANS - beta 1
receptor activation stimulates the heart
ANS - beta 2
receptor activation causes relaxation and dilation
Atropine effects on eye
Dilate the pupil
Atropine effects on heart
Atropine increases the heart rate and improves the atrioventricular conduction by blocking the parasympathetic influences on the heart
Muscarinic antagonists
- atropine = heart failure (bradycardia), premedication
- ipratropium = asthma
- hyoscine = nausea
- pirenzepine = peptic ulcer
Adrenaline
- anaphylaxis
- cardiac failure
Phenylephrine
- nasal decongestion
Salbutamol
- asthma
Prazosin
- hypertension
Beta blocker - propranolol, metoprolol
- anxiety
- angina, cardiac arrythimias
- hypertension
An antagonist that lowers the maximum efficacy of an agonist is a?
Non-competitive antagonist
The potency of a competitive antagonist is quantified using what scale?
pA2
What is a prodrug?
A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug
Example of a prodrug
Paracetamol and aspirin
Postganglionic fibres of the sympathetic nervous system are stimulated by which neurotransmitter?
Noradrenaline
A craniosacral outflow is an anatomical characteristic of the?
Parasympathetic NS
What effect would kidney failure have on the half life?
Increase
Atropine will have which effects?
Bradycardia and dry mouth
What should never be taken with aspirin?
Paracetamol
Propranolol is a?
Beta receptor antagonist
