6. NEUROHORMONES Flashcards
What are the 8 principal endocrine glands of the body?
- HYPOTHALAMUS
- PITUITARY GLAND
- THYROID GLAND
- ADRENAL GLAND
- Adrenal cortex = Aldosterone, cortisol
- Adrenal medulla = Adrenaline, noradrenaline - PARATHYROID GLAND
- PANCREAS
- OVARY
- TESTES
What hormones does the anterior & posterior pituitary release?
- Anterior pituitary = ACTH, FSH, LH. TSH, GH, PRL
- Posterior pituitary = oxytocin & vasopressin (ADH)
What hormones does the adrenal medulla & cortex release?
- Adrenal medulla = Adrenaline, Noradrenaline
- Adrenal cortex = Aldosterone, cortisol
Describe the principles of the endocrine system
- Mediators travel in the blood stream, slow communication but long term effect
- Chemical mediators - hormones
Describe the principles of the nervous system
- The nervous system has fast communication but the effects are short lasting or temporary
- Transmission of electrical impulses
What are neurohormones?
- Neurohormones are produced by NEUROSECRETORY CELLS which are specialised nerve cells
- The neurohormones are then released into the blood & act on receptors at a distance
- However, neurohormones can also act as neurotransmitters, autocrine (self) or paracrine (local) factors
Give three classes of hormones
- PEPTIDE/PROTEIN - synthesised as large precursors which can be cleaved or post-translationally modified.
- E.g FSH, LH, TSH - AMINO ACID DERVIATIVES - Hormones derived from tyrosine, can also act as neurotransmitters
- E.g adrenaline, noradrenaline - STEROID HORMONES - Lipids that are derived from cholesterol
- E.g sex steroids , cortisol
How are the hypothalamus & pituitary associated?
- The hypothalamus & pituitary are joined by the HYPOPHYSEAL NERVE TRACT
- The infundibulum of the pituitary stalk also connects the two structures
How do hormones released by the hypothalamus act on the pituitary?
- Neurohormones synthesised by the hypothalamus will be carried by neurones projecting into the pituitary
- The neurohormones will be released into the hypophyseal portal circulation which is a capillary network & portal vein system
- The hormones will then be released from the pituitary gland
What are the two major hypothalamic neurones?
- Magnocellular neurones
2. Parvocellular neurones
Describe the magnocellular neurones
- The magnocellular neurones project from the hypothalamus to the posterior pituitary
- The posterior pituitary is also known as neurohypophysis & produces vasopressin & oxytocin
- The cell body of the magnocellular neurones is located in the hypothalamus but it projects to the pituitary
- Magnocellular neuronal cell bodies are located in the:
1. Paraventricular nuclei
2. Supra optic nuclei
Describe the parvocellular neurones
- Parvocellular neurones project from the hypothalamus to anterior pituitary
- The anterior pituitary is also known as adenohypophysis
- The neurohormones will be released from the neurones into the capillary network to activate specific cells of the pituitary
What does corticotrophin releasing hormone do?
- CRH released from hypothalamus
- CRH acts on corticotrophs of anterior pituitary
- ACTH released from anterior pituitary
- Cortisol released from adrenal cortex
What does the thyrotrophic releasing hormone do?
- TRH released from hypothalamus
- TRH cats on thyrotrophs of anterior pituitary
- TSH released from anterior pituitary
- Thyroid hormones released from thyroid gland
What does growth hormone releasing hormone do?
- GHRH controls release of GH from anterior pituitary
What does somatostatin do?
- Somatostatin/ Growth hormone inhibiting hormone inhibits the release of GH, VIP, TSH, PRL & insulin
What are the specialised cells of the anterior pituitary?
- Gonadotrophs - release FSH & LH in response to GnRH
- Corticotrophs - Release ACTH in response to CRH
- Thyrotrophs - Release TSH in response to TRH
- Somatotrophs - Control LH in response to GHRH
- Lactotrophs - control PRL, in response to dopamine, somatostatin, TRH
What is ACTH & what does it do?
- ACTH (adrenocorticoptrophin hormone) is released in response to CRH produced by the hypothalamus
- ACTH stimulates the release of glucocorticoids (cortisol) & sex steroids (androgens) from the zona fasciculata of the adrenal cortex
Describe the mechanism of cortisol release via the HPA axis?
- CRH released from hypothalamus
- CRH acts on corticotrophs of anterior pituitary
- Anterior pituitary releases ACTH
- ACTH causes release of cortisol & adrenal androgens from adrenal cortex
How do cortisol levels change throughout the day?
- Cortisol levels are highest in the morning & decline throughout the day due to the pattern of ACTH secretion from the anterior pituitary
Describe the HP-Thyroid axis
- TRH released by hypothalamus
- TRH acts on thyrotrophs of anterior pituitary
- TSH released from anterior pituitary
- Thyroid hormones released from thyroid glad (T3 & T4)
What are the two thyroid hormones?
- T3 - TRIIODOTHRYOXINE
- T4 - THYROXINE
- T4 can be converted to T3 with DEIODINASE
- T4 is responsible for basal metabollic rate, high T4 = weight loss
Describe the synthesis of vasopressin & oxytocin?
- Vasopressin & oxytocin are released from the posterior pituitary
- They are synthesised in the supraoptic & paraventricular nuclei of the magnocellular neurones which project into the posterior pituitary, where they’re released
What is vasopressin & it’s effects?
- Vasopressin is also known as antidiuretic hormone
- It’s released from the posterior pituitary in response to changes in osmoreceptors of the hypothalamus
1. Controls osmolalilty - regulates water excretion & thirst
2. Stimulates contraction of smooth muscle of the kidney to cause vasoconstriction - Both of these changes help to regulate blood volume
Describe RAAS & it’s interaction with the hypothalamus to release ADH
- A drop in blood pressure or plasma volume causes teh kidneys to release RENIN
- RENIN converts ANGIOTENSINOGEN into ANGITENSIN I
- ANGIOTENSIN I circulates in the blood & is converted to ANGIOTENSIN II
- ANGIOTENSIN II causes vasoconstriction
- ANGIOTENSIN II is detected by the SUB-FORNICAL REGION
- Neuronea of the sub-fornical region project to the magnocellular neurones of the hypothalamus releasing vasopressin/ADH
- Vasopressin affects the kidneys & increases water retention to regulate blood volume
What is oxytocin?
- Oxytocin is synthesised in the hypothalamus & is released by the posterior pituitary
- Oxytocin levels can elevated during lactation & mating
- Oxytocin can be produced in response to cervical stretch receptors, stroking, grooming etc.
What are the peripheral effects of oxytocin?
- Stimulates contraction of uterine wall smooth muscle during labour
- Contracts myoepithelial cells of mammary glands - lactation
- Contracts reproductive duct during sperm ejaculation in males
What are the central nervous system effects of oxytocin?
- Oxytocin can be released into central areas of the brain such as the cortex
- The functions of oxytocin in these areas are not well understood, but it’s thought to be involved in trust, empathy, social bonding & cognition
- It can therefore be used as treatment for autism, OCD, depression
Give examples of hormones that bind to a tyrosine kinase receptor?
- Growth hormone
- Insulin
Describe the mechanism of action for tyrosine kinase receptors
- (GH or insulin) Peptide hormone binds to tyrosine kinase receptor
- Leads to dimerisation of the receptor
- Activates tyrosine kinases (JAK2/MAPIC)
- Tyrosine kinases phosphorylate target proteins to cause signalling cascade
Give examples of hormones that bind to a G-protein adenylate cyclase receptor?
- TSH
- ACTH
Describe the pathway for G-protein adenylate cyclase receptors
- TSH or ACTH bind to receptor & activate Gs or Gi protein
- Adenylate cyclase can be stimulated or inhibited depending on G protein
- Stimulation of AC= increased cAMP & increased PKA
- PKA phosphorylates target proteins to cause signalling
Give examples of hormones that bind to a G-protein phospholipase C receptor?
- Oxytocin
- GnRH
Describe the pathway for G-protein phospholipase C receptors
- Oxytocin & GnRH bind to receptor coupled to Gq
- Phospholipase C is activated which converts PIP2 -> IP3 + DAG
- IP3 causes increase in intracellular Ca2+
- DAG activates PKC which phosphorylates target proteins
Give examples of hormones that bind to a nuclear receptor?
- Sex steroids (testosterone, oestrogen)
- Cortisol
Describe the pathway for nuclear receptors receptors
- Steroid hormones pass through cell membrane as they’re lipophillic, don’t act on surface receptors
- Bind to receptors within cytoplasm to form hormone-receptor complex
- Hormone-receptor complex enters nucleus
- Hormone-receptor complex acts as a transcription factor by binding to a motif in the DNA sequence
- Initiates protein synthesis
What are diseases caused by too much GH & PRL?
- Too much GH = Acromegaly or Gigantism
- Too much PRL = Hyperprolactinaemia
What is hyperthyroidism & hypothyroidism?
- Hyperthyroidsim = too much thyroid hormone
- Hypothyroidism = too little thyroid hormone
Give an example of a hypothyroidism disease
- Hashimoto’s disease = too little thyroid
- Autoimmune disease, antibodies to thyroid hormone
- Causes: Radioactive iodine treatment, thyroid surgery, pituitary dysfunction
Give an example of a hyperthyroidism disease
- Grave’s disease = too much thyroid
- Autoimmune disease, antibodies attack thyroid gland which mimic TSH causing thyroid production
- Symptoms: fatigue, goitre, anxiety, weight loss
What is adrenal insufficiency & give an example of a disease
- Adrenal insufficiency is when too little adrenal hormones are produced e.g cortisol. The adrenal glands don’t produce enough cortisol
- Addison’s disease is an example of primary adrenal insufficiency
- Symptoms: fatigue, darkened skin, irregular menstruation
What is Cushing’s syndrome?
- Cushing’s syndrome occurs when there’s too much cortisol production
- Causes:
- External steroids (medications e.g asthma)
- Surgery
- Adrenal adenoma
- Cushing’s disease - produces too much ACTH leading to too much cortisol
What’s the difference between Cushing’s disease & Cushing’s syndrome?
- Both Cushing’s disease & Cushing’s syndrome result in elevated cortisol levels but have different cortisol
- Cushing’s disease can lead to Cushing’s syndrom
- In Cushing’s disease, a pituitary adenoma scretes too much ACTH which results in adrenal hyperplasia causing too much cortisol
- Whereas, Cushing’s syndrome is simply an increase in cortisol due to other reasons
