Puberty Flashcards
What is puberty?
- developmental event
- leading to somatic and sexual maturation
-profound physiological, psychological and physical changes - reproductive perspective: goal to produce mature gametes (spermatozoa and oocyte)
- breast development in females and increased testicular volume in males
What is adrenarche characterised by?
- first endocrine process of puberty
- occurs around 6-8 y/o
characterised by re- instigation of adrenal androgen secretion- DHEA (after 5yrs).
-androgen secretion from zona retcularis
-no change in cortisol
What are two endocrine events of puberty?
- Adrenarche->adrenal androgens
- Gonadarche -> LH/FSH
How does adrenal remodelling occur during development?
- fetus /neonate = DHEA produced
- infant - 5 y/o = no DHEA
-6 y/o = functional ZR developed - DHEA and 12- 13 ZR expansion.
histology of adrenal gland
outside -> inside
- zona glomerulosa (ZG)
-Zona fasciculata (ZF)
-Zona reticularis (ZR
-medulla (M)
How is DHEA made?
- cholestrol is the main precursor
-cholestrol -> pregnenolone -> 17 alpha hydroxypregnenolone -> DHEA -> DHEA - sulfate
What is the function of DHEA?
adrenal -> circulation -> peripheral tissue (hair follicle, genital skin for pubic hair)
Can ACTH instigate adrenarche?
- ACTH?
-children with ACTH receptor mutation fail to undergo adrenarche so maybe ACTH is involved
=> but no change in ACTH/cortisol during adrenarche so maybe not
What other factors instigate adrenarche?
- POMC?
- proximal 18 AA region that positively regulated adrenal androgen production.
-in vitro studies did not substantiate this - POMC - related peptides?
- b- lipotrophin and b-endotrophin plasma levels correlate with increase DHEA/S at adrenarche but no direct causal link - other factors ruled out include , IGF- 1 and insulin
=> no conclusive mechanism for control of adrenarch e
What comes first?
Adrenarche before gonadarche
What is gonadarche?
- reactivation of the HPG axis
- several years after adrenarche (typically ~11yrs)
- driven by hypothalamic GnRH and pituitary gonadotrophins
-puberty depends on reactivation of GnRH release
Why can we find out gender only on week 20 scan?
- HPG axis needs to be switched on to identify gender
- only switched on in week 16 and switched off just after birth then again switched on between 1-2
GnRH and puberty
Neurones restrained during postnatal period until 10 years or more.
At puberty a gradual rise in pulsatile release - around 1 year before breast budding is observed.
GnRH levels high at night
What is consonance?
- individual goes in order from stage 1 to 5 of the tanner stages of puberty.
- what varies is the duration a person stays at each stage
What are the 5 stages of Tanner stages?
- 3 categories : breast development(girls), pubic hair development, genital development (boys)
- 1 : no breast, no pubic hair and prepupertal genital
-2: breasts bud , few hairs, testis enlarged to 4mL
-3: enlarged breast and areola , more pigmented hair , penis enlarges in length.
-4: projection of areola above breast , small adult configuration, growth of penis in length and diameter
-5: papilla projects out of areola, adult configuration with hair spread onto inner thighs, testis, scrotum and penis adult size.
Why is timing of puberty(early) so important?
There are potential risks from early puberty :
-CVS disease
-metabolic disease
-obesity
- diabetes
-disordered behaviour
- decreased adult height
- decreased life expectancy
What controls onset of puberty?
- dialogue between our individual genetics and environmental factors
- all have an effect at different points of the HPG axis
Excess energy and fat causes earlier puberty = age of onset of puberty in USA and Uk is younger
Theory:
- inherent maturation of CNS
- body fat/nutrition - leptin/chrelin
-hypothalmic hormones - kisspeptin
- latest theory : epigenetics
how has onset of puberty changed?
- menarche onset is at an earlier average age 12.5 y/o in UK - trend in europe and USA also similar
- link between energy and homeostasis and reproduction
- extremes of energy excess(body fat mass) impact the timing of puberty in both sexes- particularly females = better diets in Uk with high energy
- under and over nutrition in feotal/ neonates alters the timing of puberty in rodents and humans
- morbid obsesity can cause precocious puberty
- critical fat mass hypothesis : a threshold % of fat/body weight is required to attain(17%) and maintain female reproductive ability (22%)
What animal studies show the link between body mass and fertility?
Leptin released from adiposetissue = fat tissue
- 1950s ob/ob Leptin KO mouse
- INFERTILE
Leptin directly excites kisspeptin in puberty
Pubertal mice in fed state = high leptin = high kisspeptin released = more GnRH and puberty
Pubertal mice starvation state = less leptin = low kisspeptin released = less GnRH and puberty
- 1994 : leptin gene clones
- ob/ob mice and humans - hypogonadotrophic , hypogonadism
- delayed /absent puberty
- can be reversed with leptin injection
- some leptin deficient patients have normal menses /LH /estrodiol
is leptin the trigger to puberty?
- obesity increases leptin levels and earlier puberty occurs
-KO leptin in rodents and humans - delayed/absent puberty - but leptin administration can not stimulate early puberty
- no leptin receptors on GnRH neurons to activate gonadarche
- threshold of leptin required to be reached for puberty but not a driver of puberty itself.
How does ghrelin influence puberty?
- Gherlin sense fasted state, to stimulate feeding and fat deposition
- in starvation (high ghrelin) decreased activity of the HPG axis
-Ghrelin decreases as puberty proceeds - Ghrelin can decrease hypothalamic Kiss 1 expression in rat
- oestradiol can also increase GHSR expression and response to ghrelin in kiss1 neurons
=> low levels of leptin and high levels ghrelin -> decreased LH
How does kisspeptin influence puberty?
Graph shows increased KISS-1 mRNA in pubertal monkey than in juvenile but about the same levels of GPR54 mRNA in both, so increased KISS1 levels is what drives puberty as the receptors remain the same
What is the effect of continuous kisspeptin infusion in the release of LH in juvenile rhesus monkeys?
- initial spike then decrease until HPG axis shuts down, this is because initially there are a lot of free GPR54 for kisspeptin to bind to causing increased release of GnRH , more LH from the pituitary but once the GPR54 receptors get used up( the receptors levels are the same , only kisspeptin level increases in pubertal monkeys compared to juvenile) there is a decline in LH secretion downstream when continuous kisspetin infused.
What is the effect of pulsatile kisspeptin administration on LH secretion in juvenile rhesus monkeys?
pulsatility is crucial for hormone function, so puberty can happen in correctly and development can happen in consonance, pulsitile release determines whether FSH or LH is secreted (FSH- slow , LH - fast)
