S2: Neuroendocrinology

Question 1

Compare signalling mechanism of hormone, neurotransmitter and neurohormone

Answer 1

HORMONE: a hormone secreting A gland cell releases a hormone into the blood which travels along and binds to its target cell.

NEUROTRANSMISSION:
Nerve cells mainly synapse with other neurones, but many do synapse with effector cells e.g. gland cells. A neurotransmitter is released that acts on neuron or target cell.

In both neurotransmission and hormone transmission, there is packaging of peptides into vesicles, the peptides are released and then the peptides interact with their receptors.

NEUROENDOCRINE TRANSMISSION
- Combination of both neural and endocrine signalling
A conventional nerve cell receives excitation and generates APs which travel down the axon and when they reach the axon terminal they cause release of a signaling molecule. But here instead we have release of a hormone into the blood. So it is a 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.

Question 2

What is paracrine, autocrine and intracrine transmission?

Answer 2

Paracrine= when something released from the cell diffuses locally and affects neighbouring cells

Autocrine= when something released acts on the cell that released it

Intracrine = something that occurs entirely within the cell

Question 3

What are neuroendocrine cells?

Give examples

Answer 3

Neuroendocrine cells are 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.

Examples:

• Chromaffin cells of adrenal medulla
• Hypothalamic magnocellular neurones
• Hypothalamic parvocellular neurones

Question 4

What 2 types of neurosecretory cells does the hypothalamus contain?

Answer 4

Magnocellular (meaning large cells)

Parvocellular (meaning small cells)

Question 5

What two lobes is the pituitary gland made of?

Answer 5

The pituitary gland itself is bi-lobed consisting of an anterior and posterior lobe. The anterior is larger and posterior smaller.

Question 6

Describe the structure of the posterior pituitary gland

Answer 6

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.

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.
So posterior pituitary is part of the hypothalamus both embyrologically and functionally, as the neurones are hypothalamic and hormones released are hypothalamic.

• We have the inferior hypophyseal artery, a capillary bed and then the inferior hypophyseal vein in posterior lobe

Question 7

Describe the structure of the anterior pituitary gland

Answer 7

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 form a second capillary bed in the anterior pituitary which then drains out through hypophyseal vein.

The anterior lobe contains 5 different types of endocrine cell that 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 parvocellular 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.

Question 8

Describe embryology of pituitary gland

Answer 8

• Envagination of the floor of the 3rd ventricle (neural ectoderm) which forms the neural tube
• Envagination of oral ectoderm (Rathke’s pouch) which forms anterior lobe
• Rathke’s pouch pinches off and wraps around the neural stalk to form the anterior lobe which leaves the posterior lobe.

Question 9

What hormones are released from the posterior pituitary gland?

Answer 9

Magnocellular neurones which project down into the posterior pituitary and store their hormones in their axon terminals until they are stimulated to release them into the blood.

The two hormones are

• Oxytocin (uterine contraction in labour and milk release during lactation from mammary glands - also neurotransmitter in brain)
• ADH/Vasopressin (Involved in osmoregulation and volume regulation)

Vasopressin and oxytocin structurally are peptide hormones (are small).

Question 10

What 5 hormones are released from the anterior pituitary gland?

Answer 10

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)

These are under feedback regulation and secreted into the general circulation.

Question 11

Mechanism of vasopressin function

Answer 11

• Vasopressin is especially released when blood volume goes down thus osmolality goes up. This is a signal of dehydration as there is loss of water so salt concentration is rising.
• This stimulates the osmoreceptors in the hypothalamus which then signal to the magnocellular neurones in hypothalamus to release ADH
• ADH leads to vasoconstriction (acting on V1a/V1 receptors on smooth muscle) and increases water retention via kidney receptors (V2) and aquaporins. This both increases blood pressure.

Question 12

Mechanism of oxytocin function

Answer 12

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.

Question 13

What are the 2 types of cells in anterior pituitary and their subdivisions?

Answer 13

Chromophobes and Chromophils

Chromophils can be broken down in acidophils and basophils

Acidophils: Growth hormones and prolactin
Basophils: TSH, ACTH, LH and FSH

Question 14

Name 5 different cells in anterior pituitary that release the 5 different hormones

Answer 14

TSH secreting cells = Thyrotrophs

ACTH = Corticotrophs

LH/FSH = Gonadotrophs

GH = Somatotrophs (A large amount of these)

Prolactin = Lactotrophs

Question 15

What stimulates and /or inhibits adrenocorticotropic hormone (ACTH) from anterior pituitary gland?

Answer 15

Stimulated by CRH (corticotropin releasing hormone)

Question 16

What stimulates and /or inhibits thyroid stimulating hormone (TSH) from anterior pituitary gland?

Answer 16

Stimulated by TRH (thyrotropin releasing hormone)

Inhibited by somatostatin (growth hormone inhibiting hormone)

Question 17

What stimulates and /or inhibits LH/FSH from anterior pituitary gland?

Answer 17

Stimulated by GnRH (gonadotropin releasing hormone)

Question 18

What stimulates and /or inhibits prolactin (PRL) from anterior pituitary gland?

Answer 18

Stimulated by TRH, GnRH, VIP

Inhibited by dopamine

Question 19

What stimulates and /or inhibits Growth hormone (GH) from anterior pituitary gland?

Answer 19

Stimulated by GHRH

Inhibited by GHIH (somatostatin)

Ghrelin produced from the stomach also appears to control its release but the important ones are the first two (stimulatory)

Question 20

Breif role of thyroid hormone, cortisol and GH

Answer 20

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)

Question 21

Describe feedback of growth hormone

Answer 21

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 (+ve) and somatostatin from the hypothalamus (-ve).
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 and on pituitary to decrease GH release in order to reduce GH levels.

Question 22

Stimulatory factors controlling GH secretion

Answer 22

GHRH
Ghrelin
Hypoglycemia
Decreased fatty acids
Starvation
Exercise, sleep
Stress

Question 23

Inhibitory factors controlling GH secretion

Answer 23

Somatostatin (GHIH)
GH (-ve feedback)
Hyperglycermia
Increased fatty acid
IGFs (insulin like growth factors)

Question 24

Function of growth hormones

Answer 24

• It stimulates production of IGF-1 (insulin like growth factors) in the liver
• It increases lipolysis = increased FFA
• Increases gluconeogenesis in liver = increased blood sugar
• Increases amino acid uptake into muscle, protein synthesis and lean body mass in muscle
• Stimulates chondrocytes = linear growth
• Stimulates somatic growth – increased organ/tissue size

Question 25

Effect IGF

Answer 25

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 for GH

Question 26

Describe Diurnal Fluctuations and time in of Growth Hormone

Answer 26

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 it 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.

Question 27

What is acromegaly?

Causes

Answer 27

Excess of growth hormone

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.

Question 28

How are pituitary adenomas classified?

Answer 28

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.