56) Neuroendocrinology

Question 1

What is endocrine signalling?

Answer 1

• Depolarization of endocrine cell membrane causes VGCCs to open allowing influx of Ca2+
• This causes mobilisation vesicles storing hormones which leads to the secretion of the hormones (via exocytosis)into the extracellular fluid
• These hormones are taken up by local capillaries and drained into circulation.
• In the CVS it it distributed throughout the body where they act on target cells that posses a receptor for the hormone
• The target cells respond to the hormone

Question 2

What is neurocrine signalling?

Answer 2

• When the cell membrane a nerve cell is depolarised by an action potential it will cause VGCCs to open leading to an influx of Ca2+
• This causes nerve cells to mobilising the vesicles that store the neurotransmitter to the synaptic terminal
• Then through exocytosis the neurotransmitter is secreted by the nerve cell and into the synapse between the nerve cell and a neuron or effector cell
• The target neuron/effector cell has receptors where the neurotransmitters bind to after diffusing after the synaptic cleft

Question 3

What is neuroendocrine signalling?

Answer 3

• When the cell membrane a nerve cell is depolarised by an action potential it will cause VGCCs to open leading to an influx of Ca2+
• This causes nerve cells to mobilising the vesicles that store the neurotransmitter to the synaptic terminal
• Then through exocytosis the neurotransmitter is secreted by the nerve cell and into the synapse between the nerve cell and a capillary (as the synapse of the nerve cell terminates near a capillary bed)
• The neurotransmitter is taken up by the capillary and enters the blood stream
• In the blood it is a hormone and not a neurotransmitter (i.e. a neurohormone) which is distributed via circulation to affect target cells in the body that have the specific receptor

Question 4

What is paracrine singalling?

Answer 4

• A type of endocrine signalling where the released hormone acts locally on adjacent/ nearby cells that posses the specific receptor
• This brings about a local response

Question 5

What is autocrine signalling?

Answer 5

• A type of endocrine signalling where hormones secreted by an endocrine cell act on the cell itself as it may posses the necessary receptor to do so

Question 6

What are neuroendocrine cells?

Answer 6

• Neuroendocrine cells are neurosecretory cells that release signalling molecules (hormones) from their synaptic terminals into the blood
• It is controlled by synaptic transmissions from many presynaptic neurones in a complex network

Question 7

How does the hypothalamus and pituitary glands work together?

Answer 7

• The hypothalamus receives a signal/impulse from the body which triggers the release of stimulating/inhibiting hormones
• These hormones travel to the pituitary gland where they either stimulate or inhibit hormone release from the pituitary

Question 8

Explain the embryonic formation of the pituitary gland

Answer 8

• In an early stage embryo there is an evagination from the floor of the neural ectoderm (3rd ventricle) downwards and an evagination of the oral ectoderm (Rathke’s pouch) upwards
• They meet and the Rathke’s pouch pinches off while the neural ectoderm remains intact
• The upward evagination (oral ectoderm) becomes the posterior lobe and the downward evagination (neural ectoderm) becomes the anterior lobe

Question 9

How is the pituitary gland perfused?

Answer 9

• Superior hypophyseal artery: Divides into a capillary network which vascularises the median eminence (floor of the hypothalamus). The capillary network then comes together to form hypophyseal portal veins that travel inferiorly to the anterior pituitary lobe. Here it forms a secondary capillary network which then drains inferiorly via hypophyseal portal veins
• Inferior hypophyseal artery: It vascularises the posterior pituitary lobe where it forms a capillary network which then drains away into a inferior hypophyseal vein

Question 10

What are parvocellular nuclei?

Answer 10

• (“Parvocellular” means containing small cells)
• They are smaller cells/nuclei with shorter axons that start in the hypothalamus and project to the median eminence (the floor of the hypothalamus)

Question 11

How do hormones that target the anterior pituitary reach their target cells?

Answer 11

• Parvocellular nuclei release their hormones into the capillaries of the median eminence (supplied by the superior hypophyseal artery)
• These hormones are carried via the portal vein to the anterior pituitary where they regulate endocrine cells activity which secretes various hormones
• The anterior pituitary contains different classes of endocrine cells which synthesise and release different hormones

Question 12

What are magnocellular neurones?

Answer 12

• Larger neurones that have large amounts of axons in the hypothalamus
• They extend from the hypothalamus down into the posterior pituitary lobe where they terminate at a capillary network

Question 13

Explain the hormonal/endocrine action that takes place in the posterior pituitary lobe

Answer 13

• Hormones that come from the posterior pituitary lobe are not pituitary but hypothalamic in origin
• The posterior pituitary is only the site from which they are secreted from the axon terminal into the capillaries via magnocellular nuclei
• They then pass into circulation via the inferior hypophyseal vein

Question 14

What hormones are pass into circulation by the posterior pituitary lobe and what are their functions?

Answer 14

• Oxytocin: A small peptide hormone that is involved in uterine contraction and milk ejection reflex
• Vasopressin (ADH): A small peptide hormone that is involved in osmoregulation

Question 15

How is osmoregulation a neuroendocrine reflex?

Answer 15

• Within the hypothalamus there are neurons that detec the osmolarity of the extracellular fluiud
• These neurones intergrate signals (due to changes in osmolarity) which regulates the output of neuroendocrine cells
• The supraoptic neurons is a hypothalamic nuclei containing magnocellular ADH secreting neurones
• They project down towards the posterior pituitary where they secrete ADH that drains into the general circulation

Question 16

What is an endocrine reflex?

Answer 16

• Detection of a signal (e.g. ECF osmolarity) is detected by neurons
• This signals are integrated and control the output of hormones

Question 17

What hormones are produced by the anterior pituitary and what do they do?

Answer 17

• Thyroid stimulating hormone (TSH): Targets thyroid glands which increases the secretion of thyroid hormones(Also called thyrotropin). It’s release is controlled via the release of Thyrotropin Releasing Hormone (TRH) from the hypothalamus
• Adrenocorticotropic hormone (ACTH): Targets cells on the adrenal cortex which releases cortisol. Their release is controlled via the release of Corticotropin Releasing Hormone (CRH) from the hypothalamus
• Luteinising hormones (LH) and Follicle Stimulating Hormone (FSH): Targets endocrine cells within the gonads resulting in production of androgens (males) and oestrogen and progesterone (females). Their release is controlled via the release of Gonadotropin-Releasing Hormone (GnRH) from the hypothalamus

Question 18

Explain the negative feedback system of hormones produced by the hypothalamus pituitary axis

Answer 18

• There are receptors for the final hormones produced by different pathways (e.g. cortisol or thyroid hormone) on their hypothalamic and pituitary cells that release secrete them
• When the final hormone binds to these receptors found on the hypothalamus and pituitary cells it results in reduced secretion of hypothalamic and pituitary hormones
• Hence as concentration of final hormone increases the secretion of hypothalamic and pituitary hormones decreases (the same is true for the reverse)
• It allows for the stabilisation of hormones in circulation

Question 19

What is the function of growth hormone?

Answer 19

• It is responsible for longitudinal growth (i.e. increasing bone length during growing phase) and development (e.g. increasing muscle and organ mass) by stimulating chondrocytes (cartilage cells that ultimately become bone)
• It affects multiple tissues and cells around the body
• Growth hormone also has metabolic functions as it couples growth to nutritional status
• It achieves its functions by increasing lipolysis of adipose tissue, increasing gluconeogenesis and increasing protein synthesis in muscles

Question 20

What factors increase the release of growth hormone?

Answer 20

• Growth-hormone releasing hormone which is a hypothalamic hormone secreted by parvocellular neuroendocrine cells
• Ghrelin (‘hunger hormone’) secreted by endocrine cells of the stomach
• Hypoglycaemia
• Diurnal rhythm
• Decreased fatty acids
• Fasting
• Exercise/sleep
• Stress

Question 21

What factors decrease the release of growth hormone?

Answer 21

• Growth hormone inhibiting hormone (also called somatostatin) which is released by parvocellular neuroendocrine cells from hypothalamic nuclei
• Growth Hormone in circulation (negative feedback)
• IGF-1 circulation which is released by the liver in response to Growth Hormones (negative feedback)
• Hyperglycaemia
• Increased fatty acids

Question 22

What happens to levels of GH during negative feedback control?

Answer 22

• The negative feedback control of GH will stabilise the concentration of GH in circulation at a set point
• This set point can be changed which changes during the course of the day

Question 23

How is hypoglycaemia combatted by Growth Hormone?

Answer 23

• Hypoglycaemia (reduced levels of blood glucose) stimulates the hypothalamus triggering the release of Growth Hormone Releasing Hormone (GHRH)
• GHRH stimulates the pituitary to release Growth Hormone (GH) which increases gluconeogenesis which increases blood glucose levels
• This increase in blood glucose levels means hypoglycaemia no longer occurs and so the hypothalamus is no longer stimulated decreasing the release of GHRH and GH
• This means it is a negative feedback system

Question 24

How does GH encourage muscle growth?

Answer 24

• This mobilises adipose tissue from storage allowing them to be used to produce energy
• This means that muscle protein will not be used in gluconeogenesis (which would take place is lipolysis did not occur)
• This means more protein is available for synthesis and so less is available for breakdown
• This is how GH stimulates growth of muscle

Question 25

How does GH encourage muscle growth?

Answer 25

• This mobilises adipose tissue from storage allowing them to be used to produce energy
• This means that muscle protein will not be used in gluconeogenesis (which would take place is lipolysis did not occur)
• This means more protein is available for synthesis and so less is available for breakdown
• This is how GH stimulates growth of muscle

Question 26

How do we test for pituitary function?

Answer 26

• We can use the effect of hypoglycaemia on the pituitary to test its function as it is a potent stimulus of GH release
• This is done by induce hypoglycaemia (i.e. giving a dose of insulin)
• If the pituitary is functional we should see an increase in GH levels and cortisol secretion

Question 27

Describe the diurnal/daily fluctuations of GH in humans

Answer 27

• In younger adults there are a few fluctuations (of concentration of circulating GH) during they day and a larger peak in the middle of the night
• In older adults the pattern is still visible however the fluctuations are much smaller

Question 28

Describe the lifetime pattern of changes in concentration of circulating GH?

Answer 28

• After birth GH rises sharply and remains at a fairly stable level during childhood
• When reaching puberty there is another sharp increase which is followed by a sharp decrease towards the end of puberty
• During the remainder of adult life it starts to decline steadily and finally drops to very low levels in old age

Question 29

What is acromegaly?

Answer 29

• The excess stimulation of growth hormone
• It is a slowly developing condition that is normally not diagnosed for years until visible symptoms are observed (e.g. enlargement of bones, facial features, etc)
• It is most commonly caused by an adenoma (a benign tumour) in the pituitary. In this case GH-secreting somatotrophs (cells) have increased in size and number causing increased secretion of GH
• It is less commonly caused by a tumour elsewhere in the body which secretes GHRH which in turn stimulates the GH secreting somatotrophs to release more GH

Question 30

What are the consequences of acromegaly?

Answer 30

• Growth effects (e.g. enlarged bones, facial features, hands, etc)
• Excess GH leads to insulin resistance. This is because GH stimulates liver to increase gluconeogenesis which will in turn increase insulin (in response to increased glucose) leading to insulin resistance
• Many patients also have impaired glucose tolerance (plasma glucose levels rise very high after intake of carbohydrates) and hyperinsulinemia
• Can also lead to dyslipidaemia (an imbalance in lipids)