Neuroendocrine Anatomy Flashcards
What are the modes/ types of communications between cells and which is the key one?
- Intracrine- signalling molecules of a cell acting within itself (acting of the molecules remains inside the cell)
- Autocrine- signalling molecules of a cell is released and these molecules then act on the cell via its receptors on the membrane (acting molecules are released out — act on the same cell membrane) (acting back on itself)
- Paracrine- signalling between a signalling cell and a target cell.
- Neurocrine- similar to Paracrine however, it occurs within the brain- molecules are secreted from neurons and they act on other neurons in the brain.
- Endocrine- hormones/ molecules are released from endocrine cell from one part of the body, these molecules then travel via blood stream to target cells on another part of the body .e.g. testosterone which is released from the testes, it travels via the blood stream and acts on the brain.
- Neuroendocrine- neurosecretory neuron which is within the brain, secrete molecules into the blood vessels which go on to act on cells in the periphery - usually the pituitary gland. (Key one)
What are the modes/ types of communications between cells and which is the key one?
- Intracrine- signalling molecules of a cell acting within itself (acting of the molecules remains inside the cell)
- Autocrine- signalling molecules of a cell is released and these molecules then act on the cell via its receptors on the membrane (acting molecules are released out — act on the same cell membrane) (acting back on itself)
- Paracrine- signalling between a signalling cell and a target cell.
- Neurocrine- similar to Paracrine however, it occurs within the brain- molecules are secreted from neurons and they act on other neurons in the brain.
- Endocrine- hormones/ molecules are released from endocrine cell from one part of the body, these molecules then travel via blood stream to target cells on another part of the body .e.g. testosterone which is released from the testes, it travels via the blood stream and acts on the brain.
- Neuroendocrine- neurosecretory neuron which is within the brain, secrete molecules into the blood vessels which go on to act on cells in the periphery - usually the pituitary gland. (Key one)
Key neruoendocrine cell types
- Neurosecretory neuron:
- project over long distance including the posterior pituitary
- release hormones into the brain (which act as neuromodulators)
- release hormones into the peripheral circulation/ portal of vessels to stimulate hormone release from the pituitary
Cell body- within the hypothalamus - which has a gene for the hormone being secreted - these are then packaged into vesicles and transported down the axon via microtubules - once vesicles are within the axon terminals they are then secreted into portal vessels which then project to posterior pituitary.
- cell body - hypothalamus (gene for a specific hormone) —— packaged into vesicles —— vesicles transported down axon via microtubules —— vesicle in axon terminal —— portal vessel —— posterior pituitary*
Example of neurosecretroy neurons:
- Parvocellular Neuronal Projection are neurons that are found within the Paraventricular Nucleus (PVN) of the hypothalamus and there is a related population called magnocellular neurons.
Brain regions near the 3V - 3rd ventricle
- at top side of 3V- wing like structure is the PVN
- median eminence- a circumventricular organ is at the bottom of 3V- at the median eminence there are axon terminals of neurons. And median eminence is a part of the brain which separates the brain from the pituitary gland. So, axon from paravocellular neurons within the paraventricular nucleus project down to the median eminence which then separates the hypothalamus from the pituitary gland.
Target of neurosecretory neurons- Anterior pituitary cells
- Neurosecretory cells do not project to anterior pituitary.
Instead these hypothalamic neurosecretory neurons project to capillaries which are found between the hypothalamus and the pituitary gland.
This capillaries are known as the superior hypophyseal artery and they release the hypothalamic releasing hormones from the axon terminals directly to the capillary plexus of the pituitary gland.
Within the hypothalamus there are neurosecretory neurons — project to capillaries of the portal circulation of the anterior pituitary gland — they then secrete tropic hormones.
Tropic hormones (5 types) — Cell type — Pituitary hormone — target organ
For example:
CRH (+) — Corticotropes — ACHT — Adrenal gland = stimulates glucocorticoid secretion
TRH (+), SRIF (-) — Thyrotropes — TSH —- Thyroid gland = stimulates thyroid hormone secretion
GnRH (+) — Gonadotropes — FSH, LH — Ovary/ Testis = reporductive function
GHRH (+), SRIF (-) — Somatotropes — GH — Liver Adipose Tissue = growth, control lipids, proteins and carbohydrates metabolism.
TRH (+), VIP(-) — Lactotropes —PRL — Mammary Gland — Milk production.
*SRIF (-)/ VIP (-) = inhibitory
*…….(+) = enhancement
Target of neurosecretory neuron - Posterior pituitary (neurohypophysis)
- distinct from anterior pituitary - because its not glandular (does not contain local population of secretory cells)
- contains the terminals of neurosecretory neurons (magnocellular) - which project from the brain and secret peptides into the pituitary capillaries which then joins the general circulation.
Target of neurosecretory neurons - Tanycytes
- these are specialised glia cells
- they are a type of ependymal cells which line the 3rd ventricle
- part of the CSF and blood-brain barrier (ARC/ME) - and they mediate communication between CSF which is also within the ventricles and the hypothalamus, additionally- because they also have large axonal projections they can call mediate communication between CSF and blood-brain barrier because the median eminence (ME) next to the accurate nucleus (ARC) is more permeable to blood-brain barrier.
- send projections into hypothalamic nuclei which is capable of nutrient and hormone sensing
- form part of neurogenic niche (new neurons and glia)
Blood-brain barrier (BBB)
- is a endothelial-glia barrier that protects the brain
- consists of tight junctions between endothelial and glial cells which contains specific transporters which control the entry and exit of substances from the brain.
- protects the brain from fluctuations in the periphery which might arise from infection, regulation or changes in circulating nurtients
How do hormones get into the brain?
Through- Circumventricular organs (CVOs):
CVOs are specialised structures in the brain that are permeable to capillaries allowing them to interact freely with bloodstream compared to the other parts of the brain where the BBB is quite restrictive. CVOs are involved with various homeostatic functions- including hormone release, osmoregulation and detecting blood-borne signals.
- CVOs are are areas of the brain with fenestrated capillaries (no tight junction)
There is:
- BBB with tight junction
- BBB at a CVO with no tight junction — and it is at the BBB-CVOs where specific brain areas are more receptive to nutrients and hormones in the circulation due to the absence of tight junction.
Tanycytes monitor CSF composition and pass information along to the CVOs.
Features of CVOs
- typically located at the midline of the brain
- close to ventricles within the brain but separated from CSF - here they are linked to ventricles via tanycyte processes which stretch into the brain
- most highly vascularised with fenestrated capillaries
Median eminence is one of the CVOs and it has a very few tight junctions
What are the two classes of CVOs within the brain?
1. Sensory CVOs
- these detect circulating factors in the blood .e.g. nutrients, hormones, ions etc.
- these sensory CVOs have a high expression receptors (receptors for hormones and other molecules).
- they have a high levels of neural output
Example of sensory CVOs:
—- Area postrema (AP)
—- Subfornical organ (SFO)
—- Organum vasculosum of the lamina terminals (OVLT)
And the purpose of this is that neurons within the sensory CVOs need to communicate information about the molecules they receive from the periphery to other brain sites.
2. Secretory CVOs
- these mediate the release if lipophobic hormones into the blood and/ or CSF
- these CVOs receives a high level of neural inputs
Example of secretory CVOs:
—- Median eminence (ME)
—- Pituitary gland (neurohypophysis = posterior lobe)
—- Pineal gland
Localisation and function of the CVOs
Sensory CVOs:
**AP** - located at the dorsal surface of medulla oblongata- near the floor of 4th ventricle in the brainstem - receives direct neural input from the periphery (vagus and carotid nerves) - contains metabolic hormone receptors (e.g. leptin) - transmit information from the periphery and crucial for the automatic regulatory functions - important for regulation of energy homeostasis and cardiovascular regulation (with its interaction to SFO) - involved in detecting circulating toxins and triggering vomiting reflex.
**SFO** - located in the rostral wall of the 3rd ventricle - SFO has extensive neuronal connectivity to other CVOs (OVLT) and hypothalamic nuclei - senses osmolarity (e.g. ions) and hormones (e.g.angiotensin) - transmits information from periphery to autonomic regulatory function - blood pressure, breathing, heart rate. - is crucial for fluid balance and cardiovascular regulation - has reciprocal connections - sends and receives connections from different parts of the brain - and because of this it is a key integrative CVOs.
**OVLT** - located in the anterior wall if the 3rd ventricle - has extensive neuronal connectivity with other CVO (SFO) and hypothalamic nuclei. - involved in osmoregulation and thermoregulation - it also integrates information on reproductive functions as well as fluid homeostasis
Secretory CVOs:
**ME** - located at the base of hypothalamus beneath the 3rd ventricle - contains neurosecretory neurons:
* secrete neuropeptide hormones into the capillaries which supply the pituitary gland
* GnRH, GHRH, Dopamine, TRH and CRH. - involved in the release of hypothalamic hormones that regulate anterior pituitary gland - has some sensory function as well
**Posterior Pituitary** - located below the hypothalamus - release hormones like oxytocin, vasopressin directly yo the bloodstream.
**Pineal gland** - located at the centre if the brain, between the two hemisphere at the posterior end of 3rd ventricle - so at the roof of 3rd ventricle - responsible for secretion of melatonin which regulates circadian rhythms.
Summary of CVOs
- two types of: sensory and secretory
- all are multifunctional: receptors for multiple hormone, transporters, ions etc
- each CVOs mediates multiple aspects of physiology- for example SFO regulates fluid homeostasis, reproduction and metabolism.
- they mediate communication between brain and periphery through circulating factors
- has extensive mono - and poly-synaptic connectivity to other brain regions including CVOs,
Mono = one neuron
Poly - multiple neurons
Hypothalamus - Overview
It’s Location, Function and Nuclei
Location:
Hypothalamus sits below the thalamus forming the ventral part of the diecephalon and within the hypothalamus there are various nuclei.
Function:
Hypothalamus has various functions such as the regulation of autonomic regulatory function- breathing, sleeping, hunger, thirst, mood, sexual behaviour, temperature control.
Hypothalamic nuclei refers to the various nuclei within the hypothalamus and these nuclei collectively regulate a wide range of physiological process, autonomic function, endocrine activity and behaviour response.
4 Main hypothalamic nuclei
1. Arcuate nucleus (ARC) - infundibular nucleus:
- located at the medial basal portion of the hypothalamus close to the ME and 3V
- sends projections to a variety of hypothalamic and extra-hypothalamic brain regions
- its main function is the regulation of feeding behaviour
- there are different neuropeptides and neuroendocrine neurons are expressed e.g. dopamine, NPY CART, GnRH, GHRH, AgRP, POMC, Kisspeptin etc.
- also contain tuberoinfundibular neurons which are dopamine neurons that regulate prolactin expression from the pituitary.
2. Ventromedial nucleus (VMN/VMH):
- located close to the ARC and DMH
- sends projections to a variety of hypothalamic and extra-hypothalamic brain regions.
- its main function in the regulation of glucose homeostasis, female sexual behaviour and male social aggression
- neuropeptide identity of neurons here are less well characterised but it is known to express neurons that contains BNDF,, Glucose- excited/ inhibited neurons and extensive expression of hormone receptors - like leptin, oestrogen and insulin receptors.
3. Suprachiasmatic nucleus (SCN):
- located above the optic chiasm rostrally in the hypothalamus
- receives projections from the eye and sends projections to a variety of hypothalamic sites (encoinding information about timing and seasonality) and pineal gland (melatonin production)
- its main role is the regulation of circadian rhythm
- contains neurons expressing: VIP, GRP and vasopressin
4. Paraventricular nucleus (PVN/ PVH)
- located close to the top of the 3V within the hypothalamus.
- sends projections to posterior pituitary and ME
- receives projections from the brainstem- ARC, SCN, limbic system (some of which are reciprocal)
- contains neurosecretory neurons:
——— Magnocellular which express Oxytocin and Vasopressin
——— Parvocellular/ pavicellular (nerve terminals residing in the ME) which express CRH, Vasopressin, Oxytocin - also contains parvocellular interneurons which projects to other brain regions
- PVN function include food intake, stress (HPA-axis), cardiovascular responsse, hormone secretion and thermogenesis.
Neurosecretory neurons have direct and indirect effects on hormone release from the pituitary
Direct effect = direct synapse between magnocellular neurons and cells of the posterior pituitary
Indirect = terminals of parvocellular neurons in ME or other hypothalamic nuclei will release different neuropeptides (GnRH, GHRH, CRG etc etc) into the portal vessels which will then supply the anterior pituitary.
