Nutrition and Reproduction

Question 1

What links fat mass to the onset of puberty?

Answer 1

• Leptin is a factor secreted by adipose tissue that acts at the brain, signalling that there is adequate fuel stores present in the body for reproductive activity
• Leptin does not initiate puberty, rather leptin is PERMISSIVE for puberty to occur

Question 2

How was leptin discovered?

Answer 2

• Leptin was discovered in mice that had a homozygous inactivating mutation of the obese gene
• These mice had a number of characteristics namely obesity and infertilty due to never going through puberty
• These mice have hypogonadotropic hypogonadism
• When exogenous GnRH was restored LH secretion is restored

Question 3

What is congenital lipase deficiency?

Answer 3

• There are rare mutations in the obese gene in humans that cause a lack of functional leptin production
• Humans with this condition experience obesity and infertilty
• It is treated with leptin replacement therapy
• Treatment with a leptin-like molecule restores FSH and LH function

Question 4

How does leptin exert its effect on GnRH neurons?

Answer 4

• Leptin receptors are found at every level of the HPG axis but the primary physiological effector for this system is the action of leptin in the hypothalamus
• GnRH neurons do not have leptin receptors, rather leptin is thought to control GnRH secretion via appeptide regulating peptides such as NPY and POMC (a-MHC) which are secreted by cells in the arcuate nucleus

Question 5

What do NPY neurons do?

Answer 5

• Neuropeptin Y neurons are found in the ARC
• These neurons are inhibited by leptin
• These neurons are orexigenic and stimulate food intake and appetite
• These neurons also inhibit reproduction (when administered NPY can abolish the LH surge)
• NPY neurons project directly to KNDy cells and inhibits their activity which leads to an inhibition of GnRH secretion and thus LH seccretion

Question 6

What do POMC neurons do?

Answer 6

• POMC neurons are found in the ARC
• POMC neurons synthesise melanocortin peptides including a-MSH
• POMC neurons and a-MSH secretion is activated by leptin
• a-MSH acts to decrease food intake and stimulate reproduction (infusion of a-MSH in a thin animal will restore reproductive function in the same way as leptin)
• a-MSH acts on KNDy cells in the ARC and activates them leading to increased secretion of GnRH and increased LH

Question 7

What occurs in the brain during under nutrition?

Answer 7

1. Undernutrition leads to low fat stores and low leptin levels
2. Low leptin levels cause an increase in NPY neuron activation and thus an increase in NPY secretion
3. Low leptin levels inhibit POMC neurons and cause a decrease in a-MHC secretion
4. High levels of NPY and low levels of MHC contribute to increased inhibition of KNDy neurons in the arcuate nucleus, in addition to this kisspeptin neurons also have leptin receptors
5. Inhibited KNDy cell activity results in lower kisspeptin production and less secretion of GnRH
6. Lower levels of GnRH result in less secretion of LH
7. Lower LH levels lead to an inhibition of reproduction

Question 8

What occurs in the brain when leptin treatment is given to a thin animal?

Answer 8

1. An increase in leptin levels occurs due to leptin therapy
2. Increased leptin cause an inhibition of NPY neurons and a decrease in NPY secretion
3. Increased leptin levels cause an increase in POMC activation and an increase in a-MSH secretion
4. Decreased NPY and increased a-MSH stimulate KNDy cells to contribute to an increase in activation (leptin receptors on KNDy cells also stimulate them)
5. Activated KNDy cells leads to increased kisspeptin secretion
6. Increased kisspeptin leads to increased stimulation of GnRH which restores GnRH secretion to normal levels
7. Restored GnRH secretion restores LH secretion
8. Restored LH secretion improves fertility