Puberty Flashcards
What are the 2 endocrine events for puberty?
Adrenarche and gonadarche
What is adrenarche?
- First endocrine process of puberty
- Occurs ~6-8 years
- Characterised by (re-)instigation of adrenal androgen secretion:
o Dehydro-epiandrosterone (DHEA)
o Dehydro-epiandrosterone sulphate (DHEA-S)
o No change in cortisol/other adrenal hormones - not a global activation of HPA axis
What happens is gonadarche?
(Re-)Activation of HPG axis:
• Several years after adrenarche (typically ~11 yrs of age).
- Driven by hypothalamic GnRH & pituitary gonadotrophins
- The initiation of production of LH and FSH
What do adrenal androgens do?
They’re responsible for:
- growth of pubic and axillary hair
- growth in height
What do LH and FSH do in puberty?
- LH: leads to steroid synthesis which leads to development of secondary sex characteristics
- FSH: leads to steroid synthesis/ the growth of testis in men/ folliculogenesis in women
Where is the androgen (DHEA/DHEAS) secretion from?
The zona reticularis (the inner most layer of the adrenal cortex)
What happens in the zona reticularis that leads to the production and secretion of androgens?
Inherent maturation of cellular compartments of adrenal cortex – There is remodelling of the adrenal cortex that occurs
When do androgens surge and peak?
Surge from around ages 6-8, Peak at mid 20s and then a decline
Describe adrenal remodelling in detail
- It begins in the foetal phase – adrenal gland has 2 zones: foetal zone and the definitive zone. Foetal zone is responsible for DHEA and DHEAS production in the foetus
- After the foetus is born there is a shrinkage of the foetal zone and this is accompanied by a drop in the DHEA/DHEAS production
- After that the definitive zone expands and differentiates into layers of the adrenal cortex (zona glomerulosa and zona fasciculata) – at this point DHEA and DHEAS production is off
- Focal islands of the zona reticularis form and expand.
- Zona reticularis develops – DHEA/DHEAS production is switched back on and the remodelling is complete. ZR is the one producing the androgens
- Up until puberty ZR expands
List the sections of the adrenal cortex from outermost to inner most.
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
- Medulla (not part of the adrenal cortex but comes after ZR)
How is DHEA/S made
Via steroidogenic conversions with the aid of steroidogenic enzymes:
- Cholesterol to pregnenolone to hydroxyprenenolone to DHEA
- CYP11A – converts progesterone into pregnenolone
- CYP17,20 lyase is responsible for DHEA production
- SULT2A1 – responsible for DHEA-sulfate
What enzyme makes DHEA?
CYP17,20 lyase
What enzyme makes DHEAS?
SULT2A1
What happens to the expression of CYP11A and CYP 17,20 lyase during puberty?
It increase in the zona reticularis
What does 3βHSD do?
It’s part of a side pathway and it converts cholesterol and pregnenolone into mineralocorticoids and glucocorticoids
What happens to 3βHSD expression ?
It reduces - during adrenarche the pathway shuts down so the pregnenolone and cholesterol makes more DHEA/DHEAS
What enzyme expression increases in the ZR during adrenarche?
SULT2A1, CYP11A and CYP 17,20 lyase
What is the function of DHEA and DHEAS?
It’s converted into DHT in the peripheral tissue – DHT is responsible for pubic hair, axillary hair, for the change in the skin gland and prostate secretions
What instigates adrenarche?
Not exactly sure but it could be:
- ACTH
- POMC (pro-opiomelanocortin)
- POMC related peptides
Evidence that ACTH instigates adrenarche?
- Dexamethasone (synthetic corticosteroid) suppresses adrenal androgen production
- Children with ACTH receptor mutations fail to undergo adrenarche.
- But no change in ACTH/cortisol during adrenarche
- Divergent mechanisms for cortisol and androgen production at adrenarche?