PHY3181 Lecture Notes - Missense Mutation, Gene Expression, Childhood Obesity
4 Jun 2018
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Week 10. Nutrition and Reproduction & TGF-B Proteins
in Reproduction
NUTRITION AND REPRODUCTION
Learning objectives:
• Fertility and Adiposity
o Endocrine mechanisms (leptin)
- Mutations in the leptin system and leptin replacement
- Role of leptin in puberty and hypothalamic amenorrhea
• Neural mechanisms (KISS, NPY and melanocortins)
- Effects of appetite-regulating peptides on reproductive function.
- Integration of the leptin-NPY/ POMC-KISS systems
• General dogma that any factor that affects food intake has reciprocal affect to regulate
reproduction
o 2 processes are tightly linked
o eg. NPY is an appetite stimulator that inhibits production
o melanocortins inhibit food intake and stimulates reproduction
o NPY and melanocortin are in the ARC -> senses changes in body weight and relay to
GNRH
• Body weight and fertility:
o Loss in body fat drives impaired fertility (negative energy balance)
o Obesity is typically impacted by other endocrine conditions such as PCOS (hard to dissect
the exact relationships)
o Being underweight or overweight can lead to impaired reproduction
find more resources at oneclass.com
find more resources at oneclass.com
• Critical mass is required for puberty and maintenance of reproductive function
o There is an energy demand required to carry pregnancy and lactation
o Low fat content = inadequate energy supply
o More widely studied n females
o High fat content = reduced lifespan due to metabolic dysfunction in adulthood
(problematic increased incidence of childhood obesity)
• Onset of puberty – age and body weight:
o Rapid decline is due to improved nutrition (increased quality of food)
o Later shift has coincided with obesity (average age in 2000 is 10-12 years)
-> there is a direct correlation
• What links fat mass to the onset of puberty?
o Factor that is secreted by fat
o This factor should act at the brain
o Tell the brain that adequate fuel stores are present for reproductive activity
o There are a number of factors that fit these criteria -> focusing on leptin
find more resources at oneclass.com
find more resources at oneclass.com
• Leptin deficient mice -ob/ob mice
o Leptin deficient mice -ob/ob mice
o C-T missense mutation in ob gene
o Results in truncated protein that is not biologically active
o Mutation of ob results in profound obesity
o The ob gene product may function as part of a signalling pathway from adipose tissue
that acts to regulate the size of the body fat depot
o No leptin = unrestrained satiety eat util the a’t reah the food
o Also never undergo puberty – o lepti = rai thiks there’s o fat = o sigal aout
adipose stores = shuts down reproduction as a way to repartition food
o Infertility is characterised by hypogonadotropic hypogonadism
-> do’t produe GNRH/LH/F“H
o Given exogenous GNRH restores LH secretion (pituitary is capable of responding)
o Lack a functional HPG axis
o Failure to undergo pubertal development
• Congenital deficiency of leptin in humans
o Very rare
o Identified in ¾ families worldwide
o Can repair fertility
-> treat with small peptide mimic of leptin (if use whole hormone will develop resistance
– antibodies)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Nutrition and reproduction & tgf-b proteins in reproduction. Learning objectives: fertility and adiposity, endocrine mechanisms (leptin) Mutations in the leptin system and leptin replacement. Role of leptin in puberty and hypothalamic amenorrhea: neural mechanisms (kiss, npy and melanocortins) > do(cid:374)"t produ(cid:272)e gnrh/lh/f h: given exogenous gnrh restores lh secretion (pituitary is capable of responding, lack a functional hpg axis, failure to undergo pubertal development, congenital deficiency of leptin in humans, very rare. Identified in families worldwide: can repair fertility. > treat with small peptide mimic of leptin (if use whole hormone will develop resistance. Leptin therapy increases gonadotrophin secretion in patients suffering congenital leptin deficiency: takes a few days for leptin to kick in, leptin is a long-term signal for levels of adipose. Leptin therapy allows puberty to occur at an appropriate developmental age: lepti(cid:374) does(cid:374)"t trigger pu(cid:271)ert(cid:455) itself. Would see increase in lh and fsh much earlier at 12 months: leptin is permissive.
