L20: Puberty and Menopause Flashcards
What is Kallman’s syndrome? What does it appear like?
- GnRH deficiency goes together with anosmia (loss of smell):
i) Because GnRH neurons start off at the back of the nose (not in the hypothalamus) and migrate through to the hypothalamus, if they don’t develop men and women can’t smell properly alongside Kallmann’s syndrome - Kallmann’s syndrome more often in males than females
- Kallmann’s results in sexual imaturity
- Also gets unicoid structure (long arms and legs)
i) Without GnRH didn’t go through puberty, so bones didn’t stop growing
What are the stages of sexual maturation?
- Adrenarche (activation of adrenal gland) – around age of 8
- Puberty
i) HPG axis activation
ii) Females: menarche (first menstrual cycle) – definitive (can record)
iii) Males: 1st ejaculation (imprecise)
What is adrenarche?
awakening of adrenal gland
What is menarche?
first menstrual period in female adolescent
When does adrenarche take place?
adrenal cortex activated ~8 yo
How does adrenarche happen?
- Increased secretion of steroids from zona reticularis (DHEA, androstenedione, testosterone)
- ?role – pubic/axillary hair – people with impaired gonadal function will still show some hair
- **not associated with timing of puberty
What are the differences in gonadotrophin secretion in pre-puberty, early puberty, mid-late puberty, adult (post puberty)?
Testosterone
- Birth: high in boys, then declines (very high for first few months, then completely switched off)
- Early puberty: secretion increases at night in boys
- Mid-late puberty: increased during day as well
Oestradiol
- Birth: very high, then declines (very high for first few months, then completely switched off)
- Puberty: secretion increases
AMH
- Neonate: high and rises steadily through childhood
- Puberty: ‘wobble’
Measured by LH levels
- pre-puberty: more or less steady and low
- early puberty: initially switched on as night pulses
- mid-late puebrty: even higher pulses, during the day as well
- adult: less pulsatility, levels more steady
check slide 8
What is the general pattern of gonadotrophin secretion in early teens and mid-late puberty?
Gonadotrophin secretion
- In early teens: nocturnal switching on, all driven from the brain, not sure why, but culminates in increased LH/FSH secretion
- Mid-late puberty: nocturnal progresses until its continuous throughout the whole day
What is hypothalamic maturation theory? How was it proven?
Hypothalamic maturation theory
- In castrated female monkeys: one does not get the high gonadotrophins, that one would get in adulthood, they do not respond, GnRH is not there to switch them on
What is menarche? what is its pattern throughout female’s life?
Menarche
- over first couple of years system is dysregulated, it is normal to have anovulatory cycles for the first couple of years after puberty
- afterwards they become regular
- towards the menopause it’s dysregulated again
What is the role of kisspeptin? What is the evidence? How is kisspeptin related to puberty?
- stimulates GnRH neurons, increases reproductive function
- transgenic mice with deleted kisspeptin receptor (GPR54) fail to progress through puberty
- peripheral administration of kisspeptin to prepubertal rats stimulates LH secretion and induces ovulation
- increase in KiSS-1 mRNA and/or GPR54 mRNA expression during puberty
- the electrophysiological response of GnRH neurons to kisspeptin increases at puberty
What happens to LH levels when kisspeptin experimentally is added?
- more pulsatility
- higher levels of LH
- Kisspeptin generates pulses of GnRH that then drive secretion of LH
How is age of puberty and body weight related?
there are two critical ranges:
- critical weight range for initiation of adolescent spurt
- critical weight range for menarche
- Weight range to hit puberty: humans- 47kg for girls, 55kg for boys, a critical range to hit puberty, can also observe this in hypothalamic amenorrhea, were women lose weight, and reproductive system switches off –> thought to be largely related to leptin
What is the role of leptin? How is it important in puberty? what is the evidence?
- secreted by fat cells
- regulates appetite and energy expenditure
- metabolic signal - control of HPG axis
- mice: homozygous mutants (-/-) are infertile, reversed by leptin treatment
- humans: leptin receptor signalling failure = obese and infertile (no GnRH secretion)
How is leptin hypothesized to be related to kisspeptin?
- Leptin has positive feedback on KiSS neurons
- Fasting decreases kiss1 mRNA? Lack of leptin?
- Where people have leptin receptor activation mutations –> get early puberty
