Puberty Flashcards
Puberty
Reproductive perspective:
Clinical Perspective:
Goal to produce mature gametes:
Testes –> spermatozoa
Ovaries –> oocyte
Females: Breast development in females
Male: Increased testicular volume in males
Two endocrine events of puberty
They both together in their efforts?
Adrenarche & Gonadarche
Independently regulated
Adrenarche produce __ to exhibit features such as:
produce Adrenal androgens
->
Growth of pubic hair, axillary hair
Growth in height
Gonadarche
LH/FSH
LH - steroid synthesis –> secondary sex characteristics
FSH - growth of testis (male)/steroid synthesis/folliculogenesis (female)
Adrenarche occurs at approximately which years?
~6-8 years
What is adenarche characterised by?
Characterised by (re-)instigation of adrenal androgen secretion
Dehydro-epiandrosterone (DHEA)
Dehydro-epiandrosterone sulphate (DHEA-S)
No change in cortisol/other adrenal hormones - not a global activation of HPA axis
No change in cortisol/other adrenal hormones - not a global activation of HPA axis
Androgen secretion is from which part of adrenal gland?
Zona reticularis
Remodelling of the adrenal cortex causes
secretion of the androgens (eventually)
adrenal gland contains two zones
Foetal and definitive zones
Developmental Stage
Foetus –> Neonate
What happens to adrenal glands. Is DHEA/S present?
Foetal zone - DHEA (YES)
—>
Involution (shrinkage) of FZ (DHEA YES but decreases)
Neonate
—>
Infant
What happens to adrenal glands. Is DHEA/S present?
Definitive zone expands into:
- zona glomerulosa
- zona fasiculata (outer layers of AC)
At this stage there is NO DHEA/S produced.
Infant –> ~3yrs
What happens to adrenal glands. Is DHEA/S present?
Zona reticularis focal island forms
At this stage there is NO DHEA/S produced.
~3yrs -> ~4-5 yrs
What happens to adrenal glands. Is DHEA/S present?
Zona reticularis focal island expands
At this stage there is NO DHEA/S produced.
~4-5 yrs –> ~6yrs
What happens to adrenal glands. Is DHEA/S present?
Funcitonal Zona Reticularis developed
There is now DHEA/S production
~6yrs –> 12-13yrs
What happens to adrenal glands. Is DHEA/S present?
Zona Reticularis expansion
There is DHEA/S production
Cholesterol ———> DHEA–>DHEA/S?
Cholesterol –>_____–> ____—> DHEA—-> DHEA/s
Enzymes involved?
CYP17 - 2 types
SULT2A1
3𝛽HSD —-> Glucocorticoids?
In adrenarche, there is an increase in _______ in the ZR.
SULT2A1
This side of (3𝛽HSD —-> Glucocorticoids?) is switched off or expressed less due to what reason?
To prevent cholesterol and pregninalone going sideways pathway but committed to making DHEA and DHEAS
DHEA/S goes to blood stream to which tissue to get converted?
What features would this then exhibit?
Converted to DHT in peripheral tissue metabolism
exhibit pubic hair, axillary hair, prostate, genital skin
As an instigator, how is ACTH thought to instigate Adrenarche?
- Dexamethasone suppresses adrenal androgen production
- Children with ACTH receptor mutations fail to undergo adrenarche.
But, NO change in ACTH/cortisol during adrenarche
As an instigator, how is POMC thought to instigate Adrenarche?
Proximal 18 AA region that positively regulated adrenal androgen production.
In vitro studies did not substantiate this
As an instigator, how is POMC-related peptides thought to instigate Adrenarche?
b-lipotrophin and b-endorphin plasma levels correlate with increased DHEA/S at adrenarche
What are the other factors ruled out for instigation of adrenarche?
Are there any conclusive mechanism for control ofadrenarche?
Other factors ruled out include prolactin, IGF-1 and insulin.
No conclusive mechanism for control ofadrenarche.
Gonadarche in simple terms
(Re-)Activation of HPG axis.
When does Gonadarche happen
Several years after adrenarche (typically ~11 yrs of age).
What is Gonadarche driven by?
Driven by hypothalamic GnRH & pituitary gonadotrophins.
HPG axis and puberty summarised
Is the HPG activated at the 16th gestational week?
Yes
Is the HPG activated before birth?
No HPG axis is not activated.
To make room for placental hormones.
Is the HPG activated after birth
Post-natal 1-2 years, HPG axis is activated.
At early puberty there is a nocturnal rise in?
Nocturnal rise in GnRH (LH)
Tanner stages and consonance
series of physical changes occuring puberty 1-5.
Consonance is the progression through each stage.
Every person has the same progression in the tanner stages, but what can differ?
- time spent in each stage
- time it takes to move from one stage to the other
What controls the onset of puberty? Generally speaking:
Dialogue between our individual genetics and environmental factors
All impinge at different points of the HPG axis
Why the fuss about precocious puberty? What conditions diseases?
- cardiovascular disease
- metabolic disease
- obesity
- diabetes
- disordered behaviour
- decreased adult height
- decreased life expectancy
What controls the onset of puberty? All the theories
- Inherent maturation of CNS
- Body fat/nutrition – Leptin and Ghrelin
- Hypothalamic hormones - Kisspeptin, other factors?
- Latest theories - Epigenetics?
Epigenetics - what is that?
Changes in phenotype however no change in structure of sequence
e.g lifestyle + diet of parents had epigenetic effects on genes passed on to us
Nutrition and body fat’s impact on onset of puberty:
3 observances + 1 observance (another card)
Extremes of energy excess (body fat mass) impact the timing of puberty in both sexes - particularly females
Under- and over-nutrition in foetal and/or neonates alters the timing of puberty in rodents and humans
Morbid obesity (females) can cause precocious puberty
critical fat mass” hypothesis
“critical fat mass” hypothesis
Threshold % fat/body weight is required to attain (17%) and maintain female reproductive ability (22%)
Leptin
tells brain you’re?
Sensor of energy sufficiency
Satiety factor - tells brain you’re full
Stimulates energy expenditure
Circulating levels directly proportional to amount of body fat
Influence of leptin on reproductive system
- hypogonadotrophic hypogonadism
- Delayed/absent puberty
- Can be reversed with leptin injection
- Some leptin-deficient patients have normal menses/LH/oestradial levels- unknown why.
Q. Is leptin the trigger to puberty?
Threshold of leptin required to be reached for puberty but not a DRIVER of puberty itself.
Ghrelin
What does it sense?
What does it stimulate?
Other attribubes
Ghrelin senses the fasted state, to stimulate feeding and fat deposition.
A bolus of ghrelin stimulates the GH/IGF axis Via GHSR.
In ‘starvation’ (high ghrelin) decreased activity of the HPG axis.
Ghrelin decreases as puberty proceeds.
Ghrelin can decrease hypothalamic kiss1 expression in rat
Low levels of leptin and high levels ghrelin
decreased LH.
Mutations of Kisspeptin have been linked with..
Abnormal development of GnRH neurones hypogonadism
Failure to enter puberty
Hypothalamic hypogonadism
Activating mutations of GPR54 precocious puberty
Phenotype (mice):
Male: small testes and epididymis, delayed spermatogenesis infertility;
Female: small oviducts, folliculogenesis-no progression to ovulation, no oestrous cycles, infertility
Integration of Kisspeptin-GnRH system with metabolic cues?
Reduced leptin in starvation, decreased GnRH secretion
Leptin directly excites Kiss1 neurones in ARC
Leptin deficiency »↓Kiss 1 mRNA in ARC
?What switches on puberty?
An integration of central and peripheral inputs determined both by genetics and environment/nutrition
