Neuroendocrinology Flashcards
Neural signalling
neuronal receptors are located very close to the release point on the other side of the synapse
Neurotransmitters
mainly from a nerve cell to a neurone to a neurone to effector cell
Neuroendocrine
combination of neurone and endocrine
Neuroendocrinology
What happens with hormone signalling?
What happens with neurotransmission? how does length of journey compare to hormones? does the receptor know where the agonist came from?
What is neuroendocrine transmission? How do they connect? What is the transduction?
What is paracrine transmission
what is autocrine transmission
what is intracrine transmission
Different signalling mechanisms are shown below, with hormones: a hormone secreting gland cell releases a hormone into the blood which travels along and binds to its target cell.
Comparing to neurotransmission, in both cases there is packaging of peptides into vesicles, the peptides are released and then the peptides interact with their receptors.
With regards to neurotransmission the release point of the peptides is very close to where the receptors are, resulting from neurosecretion of a neurotransmitter.
The receptor doesn’t know whether the agonist has come from a few nm away from an axon terminal or from many micrometres away via the circulation. The receptor binding is the same.
• Nerve cells mainly synapse with other neurones, but many do synapse with effector cells e.g. gland cells.
Finally, there is neuroendocrine transmission, this is a combination of both neural and endocrine signalling.
Here, we can see a conventional nerve cell, that receives excitation and generates APs which travel down the axon and when they reach the axon terminal they cause release of a signalling molecule. But here instead we have release of a hormone into the blood = neurohormone.
Then in the blood it circulates around acting like a normal hormone. In this process there has been transduction of an electrical signal to a chemical one.
When we release something from a cell that just diffuses locally and affects neighbouring cells = paracrine transmission.
Autocrine: cells release things and what it has released affects its own growth.
Intracrine: something that happens entirely within the cell.
Neuroendocrine cells: neurosecretory cells that release signal molecules (hormones) from their synaptic terminal into the blood. This is controlled via synaptic transmission from presynaptic neurones – neuroendocrine integration.
Hypothalamo-Pituitary Axis
what are the two parts?
how many lobes does the pituitary have? which one is bigger?
The pituitary we always consider in part of the hypothalamus, the hypothalamo-pituitary axis.
The hypothalamus contains two main types of neurosecretory cells, the magnocellular (meaning large cells) and parvicellular (meaning small cells).
The pituitary gland itself is bi-lobed consisting of an anterior and posterior lobe. The anterior is larger and posterior smaller.
Posterior Pituitary
How is this in relation to hypothalamus location wise?
what are magnoceullar cells?
what type of circulation goes to the glands? Name the arteries and veins that go to posterior pituitary
What hormones are produced and what are they produced by? where will they be stored and how are they released?
describe how the posterior pituitary is linked to hypothalamus
The posterior pituitary (also called neurohypophysis) is like a downward extension of the hypothalamus. The magnocellular cells are hypothalamic cells that axons travel down into the posterior pituitary and terminate there.
There are dual circulations for the anterior and posterior pituitary gland.
• We have the inferior hypophyseal artery, a capillary bed and then the inferior hypophyseal vein in posterior lobe.
Hypothalamic hormones (oxytocin and vasopressin) produced by the magnocellular neurones, will be stored in the axon terminal in vesicles and when electrically stimulated the hormones will be released and enter the circulation.
Posterior pituitary is part of the hypothalamus both embryologically and functionally, as the neurones are hypothalamic, and hormones released are hypothalamic.
Anterior Pituitary
outline the blood supply to the anterior pituitary (arteries, the median eminence and the vein)
how many types of endocrine cells does the anterior lobe contain?
what is the pars distalis?
what is the neuronendocrine neurones in anterior lobe and where do they project?
Where do they drain and what do they do there?
The anterior lobe is different, it receives blood from the superior hypophyseal artery, which forms two capillary beds, first at the base of the hypothalamus, called the median eminence (forms floor of hypothalamus) and these join to become the portal veins which then forms a second capillary bed in the anterior pituitary which then drains out through hypophyseal vein.
The anterior lobe contains 5 different types of endocrine cells which secrete in an endocrine way (also called adenohypophysis, contains pars distalis, location of most secretory cells).
But there still is a neuroendocrine element as the parvicellular neurones project into the median eminence.
So, when the hormones are released into the median eminence they drain into the portal veins and enter into the second capillary bed where they hormonally stimulate the various cells of the anterior pituitary.
Embryology of the Pituitary Gland
what forms the neural tube?
what invagination forms the anterior lobe?
How is the posterior lobe formed?
- There becomes an invagination of the floor of the 3rd ventricle (neural ectoderm) which forms the neural tube.
- There then develops an invagination of the oral ectoderm (called Rathke’s pouch) which forms the anterior lobe.
- Rathke’s pouch pinches off and wraps around the neural stalk to form the anterior lobe. This leaves the posterior lobe.
Posterior Pituitary Hormones
Where are the hormones stored?
what two hormones are released? What are they derived from? general function of both hormones?
When are they released?
what cells act as detectors for these hormones?
the magnocellular neurones project down into the posterior pituitary and store their hormones in their axon terminals until they are stimulated to release them into the blood.
Two hormones are released, oxytocin and ADH (also called vasopressin or AVP – arginine vasopressin).
ADH is involved in volume regulation while oxytocin as released by the pituitary is involved in uterine contraction during labour and milk release during lactation (mammary glands). It is also neurotransmitter in the brain.
Posterior Pituitary Hormones: Oxytocin and Vasopressin
• Vasopressin and oxytocin structurally are peptide hormones (are small).
Vasopressin is especially released when blood volume goes down and thus osmolality goes up. This is a signal of dehydration, as there is a loss of water so salt concentration is rising.
This stimulates osmoreceptors in the hypothalamus, which then signal to the magnocellular neurones in the hypothalamus to release vasopressin.
This then has its effects, leading to vasoconstriction increasing BP and also increases water retention via the kidney.
Oxytocin’s main function during labour is caused by stretch of the cervix leading to oxytocin release resulting in increased contractions of the cervix/uterine, which leads to more release, this is a positive feedback mechanism.
There are also sensory receptors in the nipples which when mechanically stimulated will result in oxytocin release causing contraction of myoepithelial cells in breast resulting in lactation.
Anterior Pituitary Cells and their Hormones
What are the 5 hormones released and what do they act on? what kind of troph are they?
There are five hormones released from the anterior pituitary:
- Thyroid Stimulating Hormone (TSH) – Stimulate thyroid
- ACTH – Acts on adrenal cortex
- FSH and LH – Testes or ovaries
- Growth Hormone (GH) – Entire body
- Prolactin (PRL) – Mammary gland (in mammals)
- [endorphins]
These are under feedback regulation and secreted into the general circulation.
Typically, histologically cells where categorised in the way shown below, given 3 classes (chromophobes, acidophils, basophils)
acidophils = gh anf prolactin basophils = tsh, acth, LH and fsh
- TSH secreting cells = Thyrotrophs
- ACTH = Corticotrophs
- LH/FSH = Gonadotrophs
- GH = Somatotrophs
- Prolactin = Lactotrophs
Control of Anterior Pituitary Secretions
What stimulates and inhibits each hormone?
How do thyroid hormone affect metabolism? talk about cortisol and GH
Why is gh different to other hormones?
primary vs secondary vs tertiary problems
High TSH and low T3/T4 = ?
Low TSH and high T3/T4 = ?
Low TSH and low T3/T4 = ?
- ACTH – Stimulated by CRH
- TSH– Stimulated by TRH, inhibited by somatostatin (growth hormone inhibiting hormone)
- LH and FSH – Stimulated by GnRH (gonadotropin releasing hormone)
- PRL – Inhibited by dopamine -> main control (also stimulated by TRH and others)
- Growth Hormone (GH) – Stimulated by GHRH, inhibited by GHIH
Thyroid hormones have massive effect on metabolism
- Cortisol in its anabolic and catabolic effects
- Growth hormone has widespread tissues, growth hormone is different to the others in that it directly affects its end endocrine target (IGF = insulin like growth factor)
The feedback control of the hypothalamo-pituitary axis means that there can be primary problems (the effector organ), secondary (with pituitary) or even tertiary (with hypothalamus).
- High TSH and low T3/T4 means there is primary hypothyroidism
- Low TSH and high T3/T4 means there is primary hyperthyroidism
- Low TSH and low T3/T4 means there is secondary hypothyroidism -> feedback not working, thyrotrophs not working.
Control of Growth Hormone Secretion
what stimulate GH release and what inhibits it? (2 most important ones)
short feedback loop and long feedback after GH release - from where?
what is a somatotrope?
where is GH released from? and what does it do after released?
how does it promote growth? (liver, muscles and fat processes)
IGFs - what are they and what do they do for growth?
LIst of stimulants
list of inhibitors
outline the general function of GH
Growth Hormone Releasing hormone controls GH release from the anterior pituitary and somatastatin (GHIH) also has an inhibitory control. Ghrelin produced from the stomach also appears to control its release, but the important ones are the first two.
There is a short feedback loop by GH and a long feedback indirectly by insulin like growth factor which is secreted by the liver in response to GH.
The predominant hypothalamic influence is GHRH
The somatotrope, a cell type in the pituitary that synthesises and releases growth hormone under the influence of GHRH and somatostatin from the hypothalamus.
The short feedback loop is simply from GH itself, GH released into the portal vein circulates around the body and when it re-circulates it acts on the hypothalamus to decrease GHRH release -> decrease GH release by pituitary -> reduce GH levels.
Growth hormone does various things to promote growth, it increases gluconeogenesis in the liver, increases protein synthesis in muscle, mobilises stored fats in adipose tissue for energy usage.
Insulin-like growth factors are synthesised by the liver in response to GH, IGFs have their own effects, including somatic cell growth, increasing chondrocyte (cartilage cells important in bone growth) function and bone modeling/remodelling.
The IGF also goes back and enters the negative feedback loop = long feedback loop.
Partial list of factors controlling GH Secretion:
Stimulatory o GHRH o Ghrelin o Hypoglycemia o Decreased fatty acids o Starvation o Exercise, sleep o Stress
Inhibitory o Somatostatin o GH o Hyperglycemia o Increased fatty acids o IGFs
GH Action:
- It stimulates production of IGF-1 in the liver
- It increases lipolysis = increased FFA
- Increases gluconeogenesis = increased blood sugar
- Increases amino acid uptake into muscle, protein synthesis and lean body mass
- Stimulates chondrocytes = linear growth
- Stimulates somatic growth – increased organ/tissue size
Diurnal Fluctuations in of Growth Hormone
when does GH peak during a day?
what is this called?
how does GH change over life? (treatments?)
We do appear to have diurnal fluctuations of GH, peaking in the early hours before waking.
This is through circadian control.
There is also changes in mean concentrations of GH throughout life, with its low levels at birth, increases and then remains stable childhood. It then surges during puberty and then decreases and continuous to slowly decrease throughout adult life and old age.
- There has been some interest in GH replacement therapy in older people.
Excess Growth Hormone: Acromegaly
what is it most commonly due to?
does negative feedback work?
what is a less common reason?
Acromegaly is most commonly due to pituitary adenoma, where there is an increase in the GH-secreting somatotrophs.
The negative feedback still works, but because the mass is so big and pumping out so much GH, the –ve feedback loop is now working at a much higher resting level. This means overall there is a rise in circulating GH.
Less commonly there is a secondary cause, which would be a tumour elsewhere secreting GHRH.
Pituitary Adenomas
the two different classifications
size of classification
symptoms of both classifications
Pituitary adenomas are classified by size and hormones they produce
- Microadenomas are <1cm
- Macroadrenomas are > 1cm
Microadenomas tend to be present with symptoms of hormonal excess
Macroadenomas, with the pituitary gland being so close to the optic chiasm, a large growth can push things apart leading to visual loss, sellar enlargement, suprasellar damage and hypopituitarism.
