Neurohormones Flashcards
List some endocrine organs of the body
- Hypothalamus
- Pituitary gland
- Thyroid gland
- Parathyroid gland
- Pancreas
- Ovary (females
- Testosterone (Male)
What does the hypothalamus do?
- Thyrotrophin releasing hormone
- Gonadotrophin releasing hormone
- Corticotrophin releasing hormone
- Growth hormone releasing hormone
What does the Pituitary gland secrete?
Anterior pituitary:
- Thyroid stimulating hormone
- Luteinising hormone
- Follicle stimulating hormone
- Growth hormone
Posterior Pituitary:
- Vasopressin
- Oxytocin
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Name the 2 main control systems of the body
- Endocrine system
- Nervous system
Describe features of the Endocrine system
- Mediators travel within blood vessels
- Utilises chemical mediators (Hormones)
- Slow communication
- Effects can be long lasting
Describe features of the nervous system
- Signalling along nerve fibres
- Transmission of electrical impulses
- Fast communication
- Effects are generally short acting
Describe features of a neurohormone
- Produced by specialised nerve cells called neurosecretory cells
- Secreted into the blood
- Have an affect of cells with some distance away
- Can also act as neurotransmitters/autocrine or paracrine messengers
List the different types of hormones?
- Protein & Peptide hormones
- Amino acid derivatives
- Steroid hormones
Give some features of a protein & peptide hormone
- Vary in size
- Can be synthesised as a precursor
- Can be processed prior to secretion
- Can be post Transcriptionally modified
- Can have multiple subunits synthesised independently and assembled
- E.g. FSH, LH, TSH
Give some features of amino acid derivatives as hormones
- Mostly tyrosine derived
- Neurotransmitter that can also act as a hormone
- E.g. Epinephrine, Norepinephrine, Dopamine
Give some features of Steroid hormones
- Steroid is a class of lipids derived from cholesterol
- Include Cortisol, Aldosterone, Testosterone, Progesterone, Oestradiol
What does the hypothalamus contain?
Contains:
- A Hypophyseal nerve tract: Found just before the start of the pituitary gland
- A Hypophyseal portal circulation: In the bulb like area
Describe the anatomy of the hypothalamo-Hypophyseal system
- The pituitary lies in the bone cavity in the sphenoid bone
- The pituitary is connected to the hypothalamus by a stalk
- The hypothalamic hormones are secreted into a Portal vein at the median eminence
- The delivery of these hormones is dependent on an intact pituitary stalk
What would happen if there was damage to the pituitary stalk?
- Any damage of the pituitary stalk will result in failure of gonadal, thyroid and adrenal function
- As well as mis-regulation of growth
What is the problem with these peptides?
They can act as both hormones and as neurotransmitters
- Sometimes the endocrine and neural functions are linked and in others they are not
Where are the neuroendocrine secretory cells found?
- They’re scattered in the hypothalamus
- The key nuclei are the medial pre-optic, the arcuate and the paragentricular nuclei
Give some Hypothalamic neurohormones which control the anterior pituitary
Briefly describe how they do so
- Corticotrophin Releasing Hormone (CRH): 41 AA peptide controlling the release of adrenocorticotrophin (ACTH)
- Thyrotrophin Releasing Hormone (TRH): 3 AA peptide controlling the release of Thyroid stimulating hormone (TSH) and Prolactin
- Gonadotrophin Releasing Hormone (GnRH): 10 AA peptide controlling the release of luteinising hormone (LH) and follicle stimulating hormone (FSH)
Give some Hypothalamic neurohormones which control the anterior pituitary
Briefly describe how they do so
- Growth hormone releasing hormone: 44 AA peptide controlling the release of growth hormone
- Growth Hormone releasing hormone (Somatostatin)
- Dopamine: A Monoamines that inhibits the release of PRL
How does the anterior pituitary respond to hypothalamic hormones?
Contains specialised cells which respond to these hormones
- Gonadotroph cells that secrete LH and FSH in response to GnRH
- Somatotrophs that control GH secretion in response to GHRH
- Corticotrophs that control ACTH in response to CRH
- Thyrotrophs that regulate TSH secretion in response to TRH
Describe ACTH as a hormone
- A 39 AA peptide
- Has a molecular weight of 4.5 kDa
- Belongs to a family of related peptide hormones derived from a large precursor glycoprotein, pro opiomelanlcortin
- Hypothalamic neurons release corticotrophin releasing hormones
- This stimulates pituitary corticotrophs to release ACTH into the circulation
- ACTH stimulates the production of glucocorticoid and sex hormones from the zona fasciculata of the adrenal cortex
Give one example of endocrine control by negative feedback (PART 1)
- Thyrotrophin releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitary to release thyroid stimulating hormone
- TSH acts on the thyroid to increase T4/T3 secretion
- T3 is the most potent thyroid hormone and target tissues contain a deiodinsxd enzyme (DI) to convert T4 to T3
Give one example of endocrine control by negative feedback (PART 2)
The pituitary also expresses deiodinase to convert T4
to T3 to facilitate negative feedback
Describe the similarities of Vasopressin and Oxytocin as hormones
- Synthesised in the supraoptic and paraventricular nuclei in the hypothalamus
- Transported to the terminals of the nerve fibres located in the posterior pituitary
- Structurally quite similar, yet have very different functions
Describe how Vasopressin in different
- Release is stimulated by changes in the activity of the osmoreceptor complex in the hypothalamus
- Controls plasma osmolality by regulating water excretion & drinking behaviour
- Stimulates vascular smooth muscle contraction in the distal tubule of the kidney to reduce water loss and raise blood pressure
Describe how Oxytocin is different
- Normally undetectable but elevated during parturition, lactation and mating
- Released in response to peripheral stimuli of the cervical stretch receptors and suckling at breasts
- It may also be involved in responses to strokes, caressing, grooming
- Regulates contraction of smooth muscle
How does the kidneys and hypothalamus interact?
- Hypothalamus secrete renin
- Angiotensin I is converted into Angiotensin II
Angiotensin II is detected by the subfornical organ - Subfornical Organ projects to vasopressin cells and neurons in the lateral hypothalamus
- Vasopressin then affects the kidneys
How is Oxytocin stimulated in the uterus
Describe the hormones mechanism of action at a cellular level for proteins (PART 1)
Mechanism of action depends on the classes of the hormone and their receptors
1. Peptide and protein hormones bind to surface receptors and activate intracellular signalling mechanisms
2. This results in alteration of target protein and/or enzyme activities
3. Binding of insulin and growth hormone to its cell surface receptors
Describe the hormones mechanism of action at a cellular level for Proteins (PART 2)
- This leads to dimerisation of the receptors
- Subsequently recruiting tyrosine kinases Which phosphorylates target protein to induce biological responses
What do mutations in the GH receptor gene result in?
- These mutations results in defective hormone binding or reduced efficiency of receptor dimerisation
- Then leads to GH resistance causing Larson syndrome
Describe the hormones mechanism of action at a cellular level for the G protein/Adenylate cyclase pathway (PART 1)
- GPCRs are the largest of the cell surface receptor groups with over 140 members
- This receptor has 7 unique transmembrane domains
- Binding of hormone to GPCR results in conformational changes in the receptor
- Leading to GTP exchange for GDP and catalytic activation of adenylate cyclase
Describe the hormones mechanism of action at a cellular level for the G protein/Adenylate cyclase pathway (PART 2)
- TSH AND ACTH bind to cell surface GPCR receptors and activate G proteins that stimulate or inhibit adenylate cyclase
- Stimulation of adenylate cyclase increases intracellular cAMP levels
- This activates protein kinase A which targets proteins
- These proteins initiate specific gene expressions and biological responses
What happens to mutations of TSH receptors?
Activated mutations of TSH receptors -> Thyroid adenomas “constitutive ON” inactivating mutations of TSH -> Resistance to TSH
Describe the mechanisms of action at cellular level for the DAG/IP3 pathway (PART 1)
- Oxytocin and GnRH bind to cell surface GOCRs and stimulate phospholipase C
- This converts phosphoridylinisitol biphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG).
- IP3 stimulates Ca2+ release from intracellular stores, particularly the endoplasmic reticulum.
Describe the mechanisms of action at cellular level for the DAG/IP3 pathway (PART 2)
- DAG activates PKC
- These stimulate the phosphorylation of proteins and alter enzyme activities to initiate a biological response
What is the result in the mutation of GnRHR?
Loss-of-function mutations in GRHR -> Sex hormone deficiency & delayed puberty (hypogonadotrophic hypogonadism
Describe the mechanism of action at cellular levels for Cytoplasmic/Nuclear receptors (PART 1)
- Steroid and Thyroid hormones can diffuse across the plasma membrane of target cells
- They can then bind to intracellular receptors in the cytoplasm or the nucleus
- These receptors function as hormone regulated transcription factors controlling gene expression
Describe the mechanism of action at cellular levels for Cytoplasmic/Nuclear receptors (PART 1)
- Nuclear receptors commonly share a transcriptional activation domain, A Zn2+ finger DNA binding domain and a ligand binding dimerisation domain
- There are more than 150 members of receptor proteins majority of which are orphan receptors
