Neurohormones Flashcards
What are the 4 different types if neuronal communication?
A: Point to point communication -activation of one neurons induces activation of one or two neurons -Fast, restricted B: Neurons of secretory hypothalamus -Neurons releases hormone directly into blood stream, hence neurohormones -slow but widespread C: Networks of interconnected neurons -Autonomic Nervous System -fast, widespread influence D: Diffuse modulatory systems -slower, widespread
What are the two main control systems that the body has?
ENDOCRINE SYSTEM:
- Mediators travel within blood vessels
- Utilises chemical mediators (hormones)
- Slow communication
- Effects can be long-lasting
NERVOUS SYSTEM:
- Signalling along nerve fibres
- Transmission of electrical impulses
- Fast communication
- Effects are generally short-acting
Neurohormones are produced by specialised nerve cells called neurosecretory cells and released into the blood.
Because they are defined as hormones, they are secreted into the blood and have their effect on cells some distance away, but the same compounds can also act as neurotransmitters or as autocrine (self) or paracrine (local) messengers
What are (3) types of hormones?
Proteins and peptide hormones:
- Vary considerably in size
- Can be synthesised as a large precursor and processed prior to secretion (e.g. GH, somatostatin, insulin)
- Can be post-translationally modified (e.g. glycosylation)
- Can have multiple subunits synthesised independently and assembled (e.g. FSH, LH, TSH)
Amino acid derivatives:
- Mostly tyrosine derived
- Neurotransmitter that can also act as a hormone
- E.g. Adrenaline, noradrenaline, dopamine
Steroid hormones:
- Steroid is a class of lipids derived from cholesterol
- Not released from neurons but have a significant affect on the CNS
- Include cortisol, aldosterone, testosterone, progesterone, oestradiol
Where are neurohormones released from?
Neuropeptides (neurohormones) are functionally important transmitters in the Hypothalamo-pituitary axis
The hypothalamus is very closely connected to the pituitary
Separated to the anterior and posterior pituitary
In the hypothalamus there is a capillary network found in the anterior pituitary and these are connected via a portal system (the hypophyseal portal circulation)
There are magnocellular neurons whose cell body in the hypothalamus and these project down to the posterior pituitary so can release neurohormones produced from the neuron nucleus (in the hypothalamus) directly in the pituitary
What is the anatomy of the hypothalamo-hypophyseal system?
The pituitary lies in a bony cavity (sella turcica) in the sphenoid bone
The pituitary is connected to the hypothalamus by a stalk
The hypothalamic hormones are secreted into the portal vein system at the median eminence
The delivery of these hormones is dependent on an intact pituitary stalk (infundibulum)
Any damage of the pituitary stalk will result in failure of gonadal thyroid and adrenal function, as well as mis-regulation of growth.
How can hypothalamic neurons release neurohormones?
The hypothalamic neurons can release neurohormones directly to the primary capillary plexus in the hypothalamus and this can get transported in the portal system to the capillary plexus in the anterior pituitary which get released to specialised cells in the anterior pituitary and these can release other neurohormones
Magnocellular neurons nuclei are located in the paraventricular nucleus and the supraoptic nucleus
And the magnocellular neurons project to the posterior pituitary where there is a capillary network which can result in the release of two important hormones; oxytocin and vasopressin in the capillary network and circulation of the body
A number of these peptides act both as hormones and as neurotransmitters; sometimes the endocrine and neural functions are linked in others they are not.
The neuroendocrine secretory cells are scattered in the hypothalamus but key nuclei are the medial pre-optic, the arcuate and the paraventricular nuclei
List the hypothalamic neurohormones that control the anterior pituitary?
Corticotrophin releasing hormone (CRH): 41 a.a. peptide that controls the release of adrenocorticotrophin (ACTH) from the anterior pituitary
Thyrotrophin releasing hormone (TRH): 3 a.a. peptide that controls the release of thyroid stimulating hormone (TSH) and prolactin (PRL) from the anterior pituitary
Gonadotrophin releasing hormone (GnRH): 10 a.a. peptide that controls the release of luteinising hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary
Growth hormone releasing hormone (GHRH): 44 a.a. peptide that controls the release of growth hormone (GH) from the anterior pituitary
Growth hormone release inhibiting hormone (Somatostatin): 14 a.a. peptide that inhibits release of GH, gastrin vasoactive intestinal polypeptide (VIP), glucagon, insulin, TSH and PRL
Dopamine: a monoamine that inhibits the release of prolactin (PRL)
What is ACTH?
Stress activates hypothalamic neurons to release CRH which will travel along the portal system to the anterior pituitary to induce release of ACTH
Adrenocorticotrophic hormone (ACTH)
ACTH is a 39 a.a. peptide
Belongs to a family of related peptide hormones derived from a large precursor glycoproteins, pro-opiomelanocortin (POMC)
ACTH stimulates the production of glucocorticoid and sex hormones from the zona fasciculata of adrenal cortex
Cortisol released from the adrenal cortex will mobilise your energy stores so you can cope with the oncoming stress
This acts via a negative feedback look inhibiting further ACTH and CRH release
How does cortisol levels differ with the circadian rhythm?
Following changes in brain activity, plasma cortisol levels are highest first thing in the morning and decline during the day (reflecting the pattern of ACTH secretion by the anterior pituitary). This circadian rhythm must be taken into account when considering cortisol replacement therapy as a clinical treatment. The pattern of cortisol secretion probably reflects the body’s response to low blood glucose after overnight fasting.
What effect does TRH have?
Thyrotrophic releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH).
TSH acts on the thyroid to increase T4/T3 secretion. T3 is the most potent thyroid hormone and target tissues contain a deiodinase enzyme (DI) to convert T4 to T3.
The pituitary also expresses deiodinase to convert T4 to T3 to facilitate negative feedback.
Thyroxin (T4) controls metabolism, heart rate and are associated with anxiety (too much) and depression (too little)
Thyroxin levels are tightly regulated via a negative feedback mechanism
Where are vasopressin and oxytocin synthesised?
Vasopressin and oxytocin
Synthesised in the supraoptic and paraventricular nuclei in the hypothalamus
Transported to the terminal of the nerve fibres located in the posterior pituitary
Structurally quite similar, yet have very different function
What are vasopressin and oxytocin?
Vasopressin:
- AKA anti-diuretic hormone (ADH)
- Release is stimulated by changes in the activity of the osmoreceptor complex in the hypothalamus
- Controls plasma osmolality by regulating water excretion and drinking behaviour
- Stimulates vascular smooth muscle contraction in the distal tubules of the kidney to reduce loss of water and raise blood pressure
Oxytocin:
- Normally undetectable, but elevated during parturition, lactation and mating
- Release in response to peripheral stimuli of the cervical stretch receptor and suckling at the breast
- It may also be involved in responses to stroking, caressing and grooming
- Regulates contraction of smooth muscles (e.g. uterus during labour, myoepithelial cells lining the mammary duct, contraction of reproductive tract during sperm ejaculation)
How does vasopressin regulate blood pressure?
In response to low blood pressure the kidney secretes renin into the bloodstream
Renin converts angiotensinogen, produced by the kidney, to angiotensin I and that gets converted to angiotensin II which induces vasoconstriction to increase blood pressure
Angiotensin II also acts on the subfornical organ
Activation of subfornical organs stimulates magnocellular neurons to release ADH from the posterior pituitary
Also induces thirst
ADH acts on the kidney to induce water retention
What role does oxytocin play during labour?
During labour the baby’s head will start pushing out and stretching the uterus
As a result, various neurons that project from the uterus to the hypothalamus will get activated
Those neurons will activate the magnocellular neurons which will project down to the posterior pituitary to release oxytocin to the blood circulation
It will start acting on the oxytocin receptors on the uterus causing uterine contractions
As the contractions take place, the baby’s head will start to move forwards activating more oxytocin release so that contractions can increase even more
This is a positive feedback loop
How do peptide hormones work at a cellular level?
The mechanism of action depends on the classes of the hormones and their receptors
Peptide and protein hormones bind to surface receptors and activate intracellular signalling mechanism that result in alteration of target protein and/or enzyme activities
Binding of insulin and growth hormone to its cell surface receptors, subsequently recruiting tyrosine kinase (e.g. JAK2 or MAPK) which phosphorylate target protein (e.g. STAT) to induce biological responses
Mutations in the GH receptor gene can result in defective hormone binding or reduced efficiency of receptor dimerisation -> GH resistance “Laron syndrome”
