Neuroendocrinology, Beyond Endo Glands

Question 1

Differentiate between neurocrine, endocrine and neuroendocrine

Answer 1

Endocrine (left)
Neurocrine (middle)
Neuroendocrine (right)

Question 2

Describe the embryology of the pituitary gland

Answer 2

The anterior lobe (adenohypophysis) is derived from oral ectoderm whereas the posterior lobe (neurohypophysis) derives from the neural ectoderm.
A thickening of cells in the oral ectoderm gives rise to Rathke’s pouch which is pinched off to eventually form the adult pituitary

Question 3

Which part of the forebrain contains some neuroendocrine cells?

Answer 3

Hypothalamus is at base of forebrain, composed of various nuclei (cell clusters). Some of these contain neuroendocrine cells. Median eminence is the floor of the hypothalamus, one of the few parts of the brain without BBB. Parvo- neurosecretory axons terminate here.

Question 4

What are parvocellular nuclei?

Answer 4

Parvocellular nuclei= smaller cells w shorter axons
Neurosecretory cells release hormones to capillaries of median eminence via the superior hypophysial artery. This is then carried by portal veins to anterior pituitary where they regulate endocrine secretion

Question 5

What are magnocellular nuclei?

Answer 5

Magnocellular nuclei= larger neurones w longer axons
Project to posterior pituitary and release to capillaries in the general circulation, supplied by inferior hypophysial artery

Question 6

Describe the posterior pituitary and the hormones it releases

Answer 6

Posterior Pit is an extension of the hypothalamus, with hormones stored in hypothalamic neuron terminals. The hormones released from here are oxytocin and ADH
These hormones are released under neural control into hypophysial capillaries, inferior hypophysial vein

Question 7

What are the functions of growth hormone?

Answer 7

Growth and development (anabolic)
Couples growth to nutritional status

Question 8

What is growth hormone controlled by?

Answer 8

Increased by: GH-releasing hormone (from hypothalamic parvocellular neuroendocrine cells)
Ghrelin (‘hunger hormone’ secreted by endocrine cells of the stomach)
Decreased by: GH-inhibiting hormone (aka somatostatin, from hypothalamic parvocellular neuroendocrine cells)
Negative feedback control by
GH in circulation
IGF-1 in circulation (released by liver in response to GH)

Question 9

List the factors that influence secretion of growth hormone

Answer 9

Question 10

Describe GH action

Answer 10

Stimulates production of IGF-1 by liver
Increases lipolysis: raises free fatty acids (FFA)
Increases gluconeogenesis: raises 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

Question 11

What is a pathological result of excess GH?

Answer 11

Acromegaly:
Most commonly due to pituitary adenoma: increase in GH-secreting somatotrophs
Less commonly secondary: tumour elsewhere secretes GHRH
Excess GH leads to insulin resistance
Many patients will have impaired glucose tolerance and hyperinsulinemia
May also have dyslipidaemia

Question 12

Describe the involvement of HSL and LPL in fat storage

Answer 12

When carb stores are full, glucose can be converted into fat and safely stored in adipose tissue, preventing lipotoxicity. 
Lipoprotein lipase (LPL) is involved in TG lipolysis into FFA so that they can be taken up by the adipocytes, and then esterified back into TG for storage. 
When needed, fat stored as TG is hydrolysed for energy use, involving hormone sensitive lipase (HSL)

Question 13

Explain why fat is an endocrine gland

Answer 13

Leptin , adiponectin and resistin are hormones secreted by adipose tissue
Also secretes cytokines
adipose tissue contains aromatase enzymes, which can convert androgens to oestrogen

Question 14

EExplain the link between leptin and obesity

Answer 14

Mutations of the leptin (LEP) gene (v rare) in adipose tissue or the leptin receptor gene in the hypothalamus lead to abnormal eating behaviour and early-onset obesity. Leptin deficiency is treated w leptin to reduce fat mass

But, more commonly, obesity is associated with leptin resistance (leptin levels are already high in obesity)

Question 15

What is the difference between healthy adipose tissue and adipose tissue in obesity?

Answer 15

Healthy adipose tissue:Leptin signals satiety to the brain
Adiponectin increases insulin sensitivity
Resistin levels low (correlated w insulin resistance)

In obesity: Leptin secretion high but hay leptin resistance
Adiponectin secretion low
Insulin resistance, diabetes and metabolic syndrome
Cytokines (e.g., IL-6, TNF-α)
Chemokines (chemotactic cytokines) attract macrophages

Question 16

What is metabolic syndrome?

Answer 16

General disorder of energy metabolism associated with
Obesity (especially visceral)
Hypertension
Hyperglycaemia (prediabetes)
High serum triglycerides (but low HDL)
Insulin resistance

Question 17

What are circadian rhythms?

Answer 17

Circadian rhythms are driven by the biological clock in the suprachiasmatic nucleus of the hypothalamus, which is located just above the optic chiasm. It uses light input to synchronize the biological clock to the night day cycle.

Sin the night day cycle, circadian rhythms still run independently but is ~25 hrs instead of 24

Question 18

Describe the human melatonin rhythm

Answer 18

Hay direct projections from the retina to the hypothalamus, specifically the SCN. Signals then travel via superior cervical ganglion to the pineal gland.
Darkness is the signal that stimulates production and secretion of melatonin by the pineal, and light inhibits it.

It seems to be involved in sleep, synchronizing it to the time of day.