Lecture 5: Puberty Flashcards
What is the definition of puberty? (reproductively and clinically)
(Complex developmental event)
- Continuum of changes leading to somatic and sexual maturation
- Profound physiological, psychological and physical changes
(Reproductively - To produce mature gametes:)
- Testes= production of spermatozoa
- Ovaries= development of meiotically competent oocyte
(Clinically)
- Breast development in females, and increased testicular volume in males
What are the endocrine events of puberty?
- Adrenarche
- Gonadarche
What is adrenarche and how is it clinically presented?
- activation of adrenal androgens (dhea/s)
- associated with:
- growth of pubic hair,
- axillary hair
- growth in height.
Definition of gonadarche
- Activation of HPG axis to produce and secrete LH/FSH
What do the 2 gonadotrophin hormones cause in gonadarche?
LH: steroid synthesis -> secondary sex characteristics
FSH: growth of testes; steroid synthesis; folliculogenesis
Is adrenarche and gonadarche dependent on one another?
-No, they are independently regulated
i.e. one does not cause the other and one does not have to start for the other to start too.
Which endocrine process of puberty is first?
- Adrenarche
At what age does adrenarche occur?
- 6-8 years
What is adrenarche characterised by? / which hormones are reinstated?
- re-instigation of adrenal androgen secretion:
- Dehydrogenase-epiandrosterone (DHEA)
- Dehydrogenase-epiandrosterone sulphate (DHEA-S)
What changes occur in adrenarche hormonally?
- DHEA and DHEA-S secretion
- No change in cortisol/other adrenal hormones
Is the HPA axis activated during adrenarche?
- Yes, BUT not globally.
Where is DHEA and DHEA-S secreted from?
- Zona reticularis
Anatomy of the adrenal gland
Why are DHEA and DHEA-S reinstated?
- Inherent maturation of cellular compartments of the adrenal cortex
- i.e. remodelling of the adrenal cortex
What happens to the adrenal gland during the foetal development stage and which hormones are present?
- 2 zones only present: foetal zone and definitive zone
- DHEA/S production
What happens to the adrenal gland during the neonate developmental stage and which hormones are present?
- Involution of foetal zone (shrinkage of foetal zone)
- DHEA/S production
What happens to the definitive zone during the infant developmental stage
- Differentiates into zona glomerulosa and zona fasiculata
At approx 3 years old, what changes are seen in the adrenal gland?
- Focal islands of Zona reticularis present (ie patches of ZR beginning to form)
At what age is the functional ZR developed and what hormones are present then?
- approx 6 years
- DHEA/S production
What is the significance of the formation of the ZR?
- DHEA/S production resumes and initiates adrenarche
Does the ZR develop as one goes into puberty? And what age is this?
- Yes, it continues to expand
- Thus there is an increase in DHEA/S production
- 12-13 years
When does adrenal remodelling start in humans?
- as a foetus
Describe the characteristics of adrenal remodelling during development from foetus to 12-13 years of age
Describe what you will see in the histology of the adrenal gland in an infant (pre-adrenarche)
Describe what you will see in the histology of the adrenal gland in a pubertal child?
- ZR developed as a result of remodelling
How is DHEA/S made?
- 3BetaHSD expression down-regulated during adrenarche
- pathway with 3betaHSD shuts down
- cholesterol able to fully commit to production of DHEA/S.
Which enzymes have an increased expression during adrenarche
- cytochrome b5
- SULT2A1
Which enzyme has a down-regulation in expression in the ZR during adrenarche
- 3BetaHSD
How do the adrenal androgens DHEA/S function?
-DHEA/S released from adrenal gland -> enter circulation -> enter peripheral tissue metabolism where they are converted to DHT
- DHEA/S aid in prostrate secretion, pubic hair follicle
What instigates adrenarche?
- No conclusive mechanism for control and regulation of adrenarche
Give examples of studies to test the instigation of adrenarche
- ACTH: Dexamethosone (synthetic cortisol steroid) suppresses adrenal androgen production; children with ACTH receptor mutations fail to undergo adrenarche; NO CHANGE IN ACTH/CORTISOL DURING 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-endorphin plasma levels correlate with increased DHEA/S at adrenarche BUT NO DIRECT LINKAGE
- Other factors ruled out include prolactin, IGF-1 and insulin
What is gonadarche?
- The reactivation of HPG axis
When does gonadarche occur?
- Several years after adrenarche (typically ~11 yrs of age).
What drives gonadarche?
- Hypothalamic GnRH & pituitary gonadotrophins i.e. HPG axis
What does puberty depend on?
- Reactivation of GnRH release
Describe the HPG axis
GnRH is synthesised & secreted
↓
Synthesis and secretion of pituitary gonadotrophins (LH & FSH)
↓
Gonadal steroid production
↓
Negatively/positively feedback onto hypothalamus-pituitary to regulate GnRH and LH/FSH production
When is the HPG axis activated and shut down during ones lifetime?
- 16th gestational week (pulsatile GnRH secretion in foetus) -> shut down just before birth
- 1-2 years postnatally -> Neurones are then ‘restrained’ during postnatal period - 10 years or more
- At puberty a gradual rise in pulsatile release- around 1 year before breast budding observed (secondary sexual characteristics)
With your understanding of the HPG axis, what is gonadarche due to?
- The reactivation of the HPG axis
Describe GnRH levels prepuberty
- constant low levels of GnRH
Describe GnRH levels early-mid puberty
- Nocturnal rise in GnRH (the study used LH as equivalent to GnRH) whilst asleep
(Nocturnal as in sleep-wake cycle - not time of day)
Describe GnRH levels mid-late puberty
- Pulsatility is consistent throughout
Describe GnRH levels in adults
- Well-established pattern
- Cyclical pattern depending on which stage of the menstrual cycle you are on
