Endocrine Flashcards
What is the endocrine system?
The system that integrates and controls organ function via secretion of chemicals (hormones) from cells, tissues or glands
Hormones carried in blood
Can either have slow or fast responses
What is endocrine communication?
Hormones travel in blood to their target organs/tissues
Tissues detect hormones through the presence of specific receptors for that chemical on/in cells
No receptor = no response
What is neural communication?
Neurotransmitters released from presynaptic neurons travel across synaptic cleft to postsynaptic cell to influence its activity.
A neurotransmitter is the chemical released by the neuron but, in contrast to hormones, acts locally within the synaptic cleft.
The endocrine and nervous systems co-operate intimately to provide further control, particularly for long-term phenomena, e.g. growth.
How does neural communication work with endocrine communication?
Nerves release hormones which enter blood and travel to their target cells e.g. hypothalamic – pituitary axis.
Although all hormones circulate throughout the body in the blood, the response to any one hormone is highly specific because only target cells have receptors for the hormone.
What is autocrine?
Cells secrete chemicals binding to same cell (cytokines)
What is paracrine?
Chemicals diffuse in ECF to affect nearby cells
Eg. Histamine
What is exocrine?
Chemicals released from exocrine glands via ducts to external environment including GI tract (saliva)
What are the features of an endocrine hormone?
Produced by a cell (or group of them)
Secreted into + transported by blood
Exert effects at very low concentrations
Act by binding to receptors on target tissues
Have their action terminated, often via negative feedback loops
What makes up a peptide/protein hormone?
Chains of amino acids
What makes up steroid hormones?
Synthesised from cholesterol
What are amine hormones made up from?
Either tryptophan
Or tyrosine
When are peptide hormones made?
Made ahead of time, then stored until required
How are peptide hormones synthesised?
Initial protein produced by ribosomes is large + inactive - perprohormone
>Preprohormones contain 1+ copies of the active hormone in their amino acid sequence
>Cleaved into smaller units in RER to leave smaller, still inactive proteins called prohormones
>packaged into vesicles in the golgi apparatus, along with proteolytic enzymes which break the prohormone down into active hormone and other fragments.
What can clinically be measured in regards to peptide hormones?
The inactive fragments in plasma
Eg C-peptide in diabetes
How are peptide hormones stored?
Hormones and fragments are stored in vesicles in the endocrine cells until release is triggered
>then all vesicle contents are released into plasma (co-secretion).
What is C-peptide?
Inactive fragment cleaved from the insulin prohormone.
Levels of C-peptide in plasma or urine are often measured to indicate endogenous insulin production from the pancreas (produced in equal amounts).
>Because insulin is metabolised faster, levels of C-peptide are typically about 5x higher than endogenous insulin release.
What is the mechanism of peptide hormones?
Water soluble - easily transported in blood
Difficult to cross cell membrane, need receptors on target cell
Once bound normally create a fast biological responses (seconds to minutes)
What pathways do peptide hormones activate?
Most work via modulating either the G-protein receptors, or tyrosine kinase pathways
How do peptide hormones activate their receptors?
Activates either a GPCR:
>rapid response through second messenger system
Or Activates a Tyrosine Kinase Linked Receptor:
> alter gene expression
> slower, longer lasting activity
What effects does the activation of peptide receptors have on the cell?
Phosphorylate existing proteins in the cell + modify their function
>open/close ion chanels,
>activate/inactivate enzymes
When are steroid hormones made, how are they transported?
Lipid soluble, so need carrier proteins (such as albumin) to carry them
synthesised as needed rather than stored (as would diffuse out of cell otherwise)
Where are steroid hormone receptors found?
Receptors located inside cells (cytoplasmic or nuclear receptors) due to easy crossing of membrane
>Trigger with activation/repression of gene function with nucleus (genomic effect)
What is the mechanisms of action of steroid hormones?
Genes control synthesis of protein so these hormones increase/decreased protein synthesis
Relative slow process - lag time between release + biological effect (hours - days)
Effect persists for a similar amount of time
What are some examples of amine hormones?
Dopamine
Adrenaline
Noradrenaline
Melatonin (only one to not be made from tyrosine)
What are the types of amine hormones?
Thyroid hormones - simialr mechanicms to steroid hormones
Catecholamines - stimilar mechanisms to steroid hormones
What is the law of mass action?
Dictates that as free hormone leaves plasma, more hormone released via carriers
Only minute Quantities of hormone required for physiological functions
What are the functions of carrier proteins?
Increases solubiity -> required for transport
Protects from degegation
Unable, when bound, to enter cells
As steroid taken up by cell, more releaed from carrier
>Creates reservoir of hormone ready for action
>Giving prolonged activity
How are hormones metabolised/secreted?
Removal via excretion or metabolic transformation - mainly occurs in the lever + kidneys
Faster for peptide + catecholamine - short life in plasma
Steroids + thyroid takes hours -days to excrete/metabolise as potein bound
How is secretion of hormones controlled?
Most via negative feedback
Some by neural feedback loops
Other hormones have additional control mechanisms
What are other factors that contribute to hormone control?
By regulating number of hormone receptors, can influnece ability for that cell to respond
>Often after prolonged exposure to low concentration, see upregulation
»Increase in number of receptors in target tissues
> Prolonged exposure to high conentration see down regulation
>Decrease in receptors on target tissues
Not only hormone’s receptors, but receptors for other hormones
What are permissive effects?
Presence of one hormone enhances effect of another
>Eg adrenaline causes lipolysis, but massive increase in amount of lipolysis when thyroid hormones also present through increased adrenaline receptors
Where is the hypothalamus located?
Hypothalamus part of brain and is directly connected to pituitary gland via a stalk called infundibulum
How does the hypothalamus communicate with the pituitary gland?
Hypothalamic communication with pituitary gland both neural (posterior pituitary) and endocrine (anterior pituitary) leads to neuroendocrine function
What type of hormones does the hypothalamus and pituitary gland (both parts) secrete?
Anterior pituitary - Endocrine hormones
Posterior pituitary - neurohormes
Hypothalamus - neurohormones
Where are the trophic hypothalamic hormones secreted to?
Into capillaries that travel to anterior pituitary
Where are the non-trophic hypothalamic hormones secreted to?
Travel to posterior pituitary before being secreted into the blood
What is the hypothalam-hypophyseal portal system and its significance?
Hypothalamus - network of tiny vessels which transfer trophic hormones to anterior pituitary
Small numbers of neurosecretory neurones sufficient for control
Hormones released from neurosecretory neurons at the median eminence
> Very small amounts of hormones required
> Short distance – very rapid and dynamic
What are the hypothalamic trophic hormones?
Thyrotrophin Releasing Hormone (TRH) Corticotropin Releasing Hormone (CRH) Growth Hormone Releasing Hormone (GHRH) Gonadotrophin Releasing Hormone (GnRH) Prolactin Releasing Hormone (PRH)
What are the hypothalamic inhibitory hormones?
Growth Hormone Inhibiting Hormone (GHIH) aka somatostatin
Prolactin Inhibiting Hormone (PIH) aka Dopamine
Describe the anterior pituitary gland
true endocrine tissue epithelial origin connected to hypothalamus via capillary portal system also called adenohypophysis makes up 2/3rds of the gland
Describe the posterior pituitary gland
neuroendocrine tissue neural tissue origin neural connection to hypothalamus secretes neurohormones made in hypothalamus also called neurohypophysis makes up 1/3rd of the gland
How does the hypothalamus control the hormone production of the anterior of pituitary?
By producing realsing and inhibiting hormones
What are the hormones produced by the anterior pituitary?
Thyroid Stimulating Hormone (TSH) aka thyrotrophin
Adrenocorticotrophic Hormone (ACTH) aka corticotrophin
Follicle Stimulating Hormone (FSH)
Luteinising Hormone (LH) - Gonadotrophin
+ FSH - gonadadotrophin
Growth Hormone (GH)
Prolactin -non-trophic hormone
Where does prolactin act, what does it do?
Acts on the breast directly
Stimulates lactation
Where does thyroid stimulating hormone act, what does it do?
On the thyroid
Stimualtes thyroid hormone release
Where does adrenocrticotrophic hormone (ACTH) act, what does it do?
In the adrenal cortex,
Stimulatesd cortisol release
Where does growth hormone act, what does it do?
Acts on liver and tissues
Stimulates tissue metabolism and IGF1 release from the liver
Where do FSH (follicle stimulating hormone) and LH (luteinising hormone), what does it do?
Act on Gonads
Regulate reproductive function and stimulate sex hormone release
How is the hypothalamus controlled by feedback?
Both short and long loop feedback inhibits hypothalmus production of trophic hormones
Hormones produced by the anterior pituitary will negatively feedback to the hypothalmus
And the hormone from the endocrine gland will negatively feedback to both the anterior pituitary and the hypothalamus
What hormones does the posterior pituitary release and store?
Vasopressin (ADH)
Oxytocin
Where are the posterior pituitary hormones synthesised?
In magnocellular neurones (cell bodies in specific areas of the hypothalamus)
>Different subsets make either vasopressin or oxytocin
How does the posterior pituitary release hormones into the blood?
axons project down the infundibulum from hypothalamus to posterior pituitary
do not synapse with other neurons, their terminals end directly on capillaries
hormones synthesised in the hypothalamus and transported to the nerve terminal in posterior pituitary ready for release
activity in these neurons results in release of vasopressin or oxytocin directly into the blood stream at the posterior pituitary
What is the function of vasopressin?
regulates water balance
What triggers the release of vasopressin?
increase in plasma osmolarity,
Decrease in plasma volume/blood pressure
Where does vasopressin act, what does it do?
Kidney collecting ducts
>Increase in water reabsoprtion
Vascular smoth muscle
>Leads to increased blood pressure
What are the main functions of oxytocin?
Milk ejection
Uterine contractions
What stimulates oxytocin release?
Labour - baby’s head against cervix
Suckling
Where does oxytocin act, what are its effects?
Milk duct smooth muscle
>Contracts muscle, ejecting milk
Uterine smooth muscle
>Child birth
What is a primary endocrine disoder?
Where there is a defect in the hormone secreting cells
What is a secondary endocrine disorder?
Where there is a defect in the amount of the trophic hormone released
What is a tertiary endocrine disorder?
A defect relating to the hypothalamus
What is the usual blood glucose?
5mmoles
What do alpha islet cells of the pancreas produce?
Glucagon
What do alpha Beta cells of the pancreas produce?
Insulin
What do delta islet cells of the pancreas produce?
Somatostatin
What do F islet cells of the pancreas produce?
Pancreatic polypeptide
How is insulin produced?
Produced by pancreatic cells
Synthesised as preprohomone - preproinsulin, converted to proinsulin in ER
Then packaged as granules in secretory vesicles
Within granules proinsulin –> insulin + c-peptide
Stored until activated.
How is insulin released by Beta islet cells?
Stimulated by glucose! + amino acids in blood:
b-cells have K+ sensitive to ATP
When glucose is abundant, it enters cells through GLUT proteins increasing metabolism
Leads to increase in ATP, closing KATP channels. Intracellular K+ rises, depolarising cell
Voltage dependent Ca2+ channels open, triggering insulin vesicle exocytosis
What is the mechanism of insulin?
Binds to tyrosine kinase receptors on cell membrane of insulin sensiive tissues (muscle/adipose) to increase glucose uptake by these tissues
>Hence lowers blood glucose
Stimulates mobilisation of specific transporters, GLUT-4
>When stimulated by insulin, it migrates into the membrane of cell able to transport glucose
How is the livers uptake of glucose dependant on insulin?
GLUT-2 transporters transport glucose into the cell down concentration gradient
Insulin has no direct effect, but glucose transport into hepatocytes affected by insulin status
>Insulin causes glucose conversion into glucose-6-phosphate keeping intracellular glucose low, allowing more glucose to transport across
What are the actions of insulin (10)?
> Transports glucose across muscle/adipose cell walls
Increases glycogen synthesis in muscle and liver. >Stimulates glycogen synthase
Inhibits glycogen phosphorylase.
Increases amino acid uptake into muscle, promoting protein synthesis.
Increases protein synthesis and inhibits proteolysis
Increases triacylglycerol synthesis in adipocytes and liver i.e. stimulates lipogenesis and inhibits lipolysis.
Inhibits the enzymes of gluconeogenesis in the liver
Has a permissive effect on Growth Hormone
Promotes K+ ion entry into cells by stimulating Na+/K+ ATPase. Very important clinically.
What stimuli increase insulin release?
- Increased [BG]*****
- Increased amino acid concentration in plasma
- Glucagon (insulin required to take up glucose created via gluconeogenesis stimulated by glucagon)
- Other (incretin) hormones controlling GI secretion and motility eg gastrin, secretin, CCK, GLP-1, GIP.
- Vagal nerve activity
What stimuli decrease insulin release?
- Low [BG]
- Somatostatin (GHIH)
- Sympathetic a2 effects
- Stress e.g. hypoxia
What do incretin hormones increase insulin release?
Released by ileum and jejunem in response to nutrients.
Early insulin release prevents glucose surge when absorption occurs.
How does vagus activity increase insulin release?
Vagus stimulates release of major GI hormones including insulin
Leads to insulin effect of IV being lesser than oral of same amount
>IV glucose leads to increase in insulin due to increased glucose on b cells
>Oral - direct effect on b cells, vagal stimulation + incretin
What is glucagon?
Formed from preproglucagon being cleaves to form glucagon + major proglucagon fragment
Raises blood glucose
What are the actions of glucagon?
Primarily opposes action of insulin - part of glucose counter-regulatory control system
Receptors are G-protein couple receptors linked to cAMP system resulting in
>Increased glycogenolysis
>Increased gluconeogensis
>Formation of ketones from fatty acids
All occur in liver
What hormones are part of the glucose counter-regulatory control system?
Glucagon
Adrenaline
Growth hormone
Cortisol
what stimulates the secretion of glucagon?
Low [BG]
High [amino acids] . Prevents hypoglycaemia following insulin release in response to aa.
sympathetic innervation and adrenaline,
cortisol
stress e.g. exercise, infection
What inhibits the secretion of glucagon?
glucose
free fatty acids (FFA) and ketones
insulin (fails in diabetes so glucagon levels rise despite high [BG] )
somatostatin
How does the autonomic nervous system, ANS, stimulate islet cells?
Parasympathtic activity (vagus) leads to increase in insulin and lesser extent glucagon to anticipate digestion
Sympatetic activation promotes glucose mobilisation
>Increase in glucagon + epinephrine
>Inhibition of insulin
What glucose counter regulatory effects does glucagon have?
Liver glycogenolysis
Gluconeogensis
What glucose counter regulatory effects does adrenaline have?
Muscle glycogenolysis
Liver glycogenolysis
Gluconeogensis
Lipolysis
What glucose counter regulatory effects does cortisol have?
Gluconeogensis
Inhibition of glucose take up
Lipolysis
Protein catabolism
What glucose counter regulatory effects does Growth hormone have?
Gluconeogensis
Inhibition of glucose take up
Lipolysis
What are the actions of somatostatin?
Also known as GHIH - inhibiting GH
Action to inhibit GI tract activity
Function appears to be to slow down absoprtion to prevent exaggerated peaks in plasma concentrations
Not a counter-regulatory hormone in control of blood glucose
>However, strongly supressses both insulin + glucagon
How does exercise affect glucose uptake?
Normally glucose absorbed through glut 4 receptors with insulin binding to it
In exercise, it increases glut-4 expression by allowing them to migrate to the membrane without insulin being present
>This allows the muscle to uptake glucose more easily
What is growth hormone?
Growth hormone - aka somatostatin
A peptide hormone bound to a carrier protein in blood which is species specific
Promotes growth
>Requires permissive action of thyroid hormones + insulin before it does so
Maintains tissues
How does growth hormone work?
Effect mediated through stimulating both cell size (hypertrophy) and cell division (hyperplasia)
Achieves effect on cell division via insulin-like growth factor 1 - IGF1
When does growth hormone become prominent in the human body?
Becomes prominent at 8-10 months
How is growth hormone regulated?
IGF 1 released mainly from liver in response to GH release from anterior pituitary
IGF1 controls GH release through negative feedback
What are the effects of growth hormone on bone?
GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes.
During the differentiation, the cells begin to secrete IGF-1 and to become responsive to IGF-I
IGF-1 than acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes
>Cuases cell division and production of cartilage, the foundation for bone growth.
What are the direct effects of growth hormone?
Increases gluconeogenesis by the liver
Reduces ability of insulin to stimulate glucose uptake by muscle + adipose tissue
Makes adipocytes more sensitive to lipolytic stimuli.
However, unlike cortisol and just like insulin, GH:
Increases muscle, liver, and adipose tissue amino acid uptake and protein synthesis.
What controls the secretion of growth hormone?
Controlled by hypothalamus which secretes GHRH and somatostatin (SS)
Large quantities of GH are present in pituitaries of both adults and children. In both, the rate of secretion undergoes rapid spontaneous fluctuations as well as increase/decrease in response to specific stimuli.
For measurement of GH - 24 hour surveillance
Massive spike in children in early hours of sleep
What stimuli increase growth hormone secretion?
Actual or potential decrease in energy supply to cells.»_space;Eg fasting, exercise cold
Increased amounts of amino acids in the plasma, eg protein meal.
»GH promotes amino acid transport and protein synthesis by muscle and liver.
Stressful stimuli eg infection, psychological stress
Delta sleep
>may be related to growth spurts in children and adolescents and tissue repair in adults.
>Oestrogen and androgens
What stimuli decrease growth hormone secretion?
Glucose
Cortisol
FFA
REM sleep
What factors contribute towards growth?
Hormones
Nutrition
Diet
What hormones contribute towards growth?
GH, IGF1, thyroid hormones, sex hormones, glucocorticoids + insulin
What are the two rapid phases of growth?
Infancy and puberty
What is the infancy growth phase?
Growth spurts arounf 2.5cm
Then nothing for a few days
I.e episodic
what is the puberty growth phase?
Sex hormones cause spikes in GH secretion
Promote bone elongation before causing epiphyseal plates to fuse
What conditions arise from hypersecretion of GH?
Gigantism (before fusion)
Acromegaly (after fusion)
