lecture 7: puberty Flashcards
1
Q
What is puberty?
A
- period of transition from adolescence to adulthood
- in humans takes 4-5 years
- development of secondary sexual characters
- many other physical and endocrine changes
- menarche - first menstruation
- first ejaculation
2
Q
What happened with the boy with a right testis interstitial cell tumour?
A
- boy age 5 years 3 months
- height = 9.5 years
- bone-age 13.5 years
- muscular build
- pubic hair
- penis large
- acne
- deep voice
- right testis swollen
- right testis: interstitial cell tumour
- seminiferous cords outside the tumour
- no maturation to spermatics or spermatozoa
- it is the leydig cells that are proliferating and therefore producing very high levels of testosterone and driving the precocious puberty seen in this boy
3
Q
What changes in growth are seen?
A
- adolescent growth spurt
- minimum growth velocity
- peak height velocity
- decrease and cessation of growth and start of epiphyseal fusion
- growth spurt in boys later than girls
- sex differences in pattern of growth
- shoulders
- hips
- growth hormone and sex-steroids
- increasing bone density
4
Q
What are the stages of puberty as defined by Tanner?
A
female
- breast development (stage 1 - 5)
- height spurt
- menarche (happens way down the track, a lot of things have happened before the first menstruation)
- pubic hair (1 - 6)
- all of these things have some sort of temporal relationship
- first ovulation occurs after first menstruation
male
- height spurt
- penis
- testis
- pubic hair
- spermatogenesis begins with first height spurt (12.5 - 13)
- apex strength spurt with second height spurt
- starts early occurs over a long time
5
Q
What is individual variation in timing of puberty?
A
- lots of individual variation
- boys all aged 14 can range from clearly pre-pubertal to clearly post-pubertal
6
Q
Does the adrenal gland make androgens?
A
- yes but much less than the gonads do (normally)
7
Q
What is Adrenarche?
A
- adrenal changes
- from 8 years old until about 13-15 years
- increased secretion of dehydroepiandrosterone DHEA and DHEAS (DHEA-sulphate)
- weak androgens but very high concentrations
- independent of glucocorticoid and mineralcorticoid
- promotion of pubic and axillary hair growth
- not closely linked to puberty - just happens to be occuring at the same time
- can be metabolised to more active androgens
8
Q
What is thelarche?
A
- pubertal changes due to oestrogens
- breast development
- hip fat distribution
- increase in vaginal cell:
- glycogen content
- secretions
- uterine development which can lead to menarche before ovulation
9
Q
What drives development of the gonads?
A
- gonadotrophins and gonadal steroids
- female
- increasing gonadotrophins (FSH and LH)
- driven by GnRH
- increasing oestradiol
- some androgens (DHEA) from adrenal
- increasing gonadotrophins (FSH and LH)
- male
- increasing gonadotrophins
- increasing androgens
- small amounts of oestrogen from testis; more from peripheral aromatisation of testosterone
10
Q
What are the levels of control for puberty?
A
Organisation
- Hypothalamus: MBH GnRH neurons: GnRH oscillator (pulse generator) frequency of pulses
- Portal vessels: GnRH: hormanal signal: pusatile
- pituitary: gonadotropes: frequency and amplitude modulated
- LH and FSH: signal, pulsatile secretion
- Gonads: testes and ovaries: activation of gonadal gonadotrophin receptors
- amplitude modulated
- testosterone and oestradiol: act via gonadal steroid receptor
11
Q
What is the gonadostat hypothesis?
A
- reflects changing characteristics in the HPG feedback system, but may be a consequence rather than cause of puberty
- note: +ve feedback system develops late in puberty in females, first cycles often anovulatory
- turn down sensitivity therefore increase levels of hormones
- seen typically in something like a sheep
12
Q
What is the maturation of the CNS seen in primates?
A
- after castration, FSH and LH rise to adult levels until week 20, then fall to basal until after 120
- result from changed GnRH output in absence of any changes in gonadal steroid levels
- similar effects seen in agondal humans - e.g. in Turner’s or Keinefelter’s syndrome
- induction of gonadotrophin pulses in immature rhesus monkey by hourly GnRh pulses over 110 days
- note first induced oestradiol peak does not induce a full LH surge
- after cessation of GnRH pulses ovarian cycles cease and subsequent implantation of an oestradiol pellet does not induce an LH surge in the absence of GnRh
- onset much earlier than normal
- the timing of puberty in rhesus monkey and humans is more related to onset of GnRH pulses induced by maturation of hypothalamus ( can be overridden with exogenous delivery of pulses)
13
Q
What is kisspeptin?
A
- found to regulate HPG axis in 2003
- various peptides derived from a 145 aa protein encoded by Kiss 1 gene
- found in hypothalamus
- act via G-protein coupled receptor GPR54
- GPR54 found on GnRH neurons
- exogenous kisspeptin stimulates GnRH secretion
- mice with disrupted Kiss 1 or GPR54 prevents puberty onset of Kiss 1 expression in hypothalamus and increased GPR54 in GnRH neurons just before puberty
- administration of kisspeptin to prepubertal rats advances onset of puberty
14
Q
Does kisspeptin drive puberty?
A
- kisspeptin neurons send terminals onto the GnRH neurons
- receptors that are responsive to kisspeptin
- stimulates GnRH release
- LH/FSH etc
- two main groups of kisspeptin neurons
- AVPV
- arcuate nucleus
- KISS neurons have steroid receptors
- the ones in the arcuate nucleus are suppressed by sex steroids
- KISS expression in AVPV stimulated by sex steroids
15
Q
A central role for kisspeptin?
A
- the whole story is very complicated
