Puberty Flashcards
Summarise Puberty (5)
- Complex developmental event
- Continuum of changes leading to somatic and sexual maturation
- Profound physiological, psychological and physical changes
- Reproductive perspective: goal to produce mature gametes:
- Testes -> spermatozoa
- Ovaries -> oocyte
- Breast development in females, and increased testicular volume in males
What is the clinical sign of puberty (male and female) (2)
male: increase in testicular vol.
female: breast development
2 endocrine events of puberty (2)
1) adrenarche: stim. of adrenal androgens = growth of pubic + axillary hair, height
2) Gonadarche: activat. of HPG Axis (LH +FSH) =>
LH= steroid synth: secondary sex characteristics
FSH= growth of testis/folliculogenesis/steroid synth
together = puberty
Adrenarche (3)
- First endocrine process of puberty : ~6-8 years
- Characterised by (re-)instigation of adrenal androgen secretion
-Dehydro-epiandrosterone (DHEA)
-Dehydro-epiandrosterone sulphate (DHEA-S) - No chance cortisol/other adrenal hormones - not a global activation of axis
DHEA/DHEAS pattern in life (7)
1)high @ birth
2) drops down (0)
3) rises at puberty (6-8)
4) rises + peaks at 20@s
5) gradual decline
- Androgen secretion is from the zona reticularis
-Result of inherent maturation of cellular compartments of adrenal cortex
Adrenal remodelling during development - 2 enzymes
Most of ZR dev. during puberty vis adrenal remodelling
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expression of SULT2A1 and shutdown of 3betaHSD
How is DHEA/S made? (5)
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1) Cholesterol
2) Pregnenolone
3) 17-alpha-Hydroxypregeneolone (using CYP17)
4)DHEA (using CYP17)
5)DHEA Sulfate (using SULT2A1)
Where is the downregulation during the creation of DHEA/S? (
side pathway/shunting of pregnenolone shut down during adrenarche to allow for all cholesterol to be committed to DHEA/S production = downregulated 3betaHSD expression
Functions of DHEA/S (4)
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1) adrenal tissue: created as cholesterol products
2) into circulation (blood)
3) peripheral tissue (e.g. prostate, hair follicle, genital skin): (as other products): converted into DHT and 5,11OHT via metabolism
4) hence pubic hair, axillary hair etc.
What instigates adrenarche? ACTH evidence (4)
But no change in ACTH/cortisol during adrenarche = NOT A CANDIDATE XXXXXXX
1) Dexamethasone (synth. steroid) suppressed adrenal androgen production
2) Children with ACTH receptor mutation fail to undergo adrenarche
Divergent mechanisms for cortisol and androgen production at
adrenarche? (not conclusive)
What instigates adrenarche? POMC evidence
Peptide: Proximal 18 AA region that positively regulated adrenal androgen production.
However:
* In vitro studies did not substantiate this (not conclusive)
What instigates adrenarche? POMC related peptides
b-lipotrophin and b-endorphin plasma levels correlate with increased DHEA/S at adrenarche
but no direct linkage established (not conclusive)
What instigates adrenarche? Other factors ruled out
Include Prolactin, IGF-1 and insulin were ruled out
= no conclusive mechanism for control of adrenarche
Gonadarche (4)
- (Re-)Activation of HPG axis.
- Several years after adrenarche (typically ~11 yrs of age).
- Driven by hypothalamic GnRH & pituitary gonadotrophins.
HPG: GnRh -> LH/FSH -> steroidogenesis
= puberty depends on the reactivation of GnRH release
HPG axis and Puberty on/off (8)
(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)
1) 16th gestational week activation of HPG axis. (sex confirmation @ 20wk scan)
2) just before birth = switched off
3) After birth: Pulsatile GnRH secretion switched on in foetus and 1-2 years postnatal increased.
4) After this: switched off - Neurones ‘restrained’ during postnatal period -> 10 years or more
5) At puberty: re-activated = a gradual rise in pulsatile release- around 1 year before breast budding observed
Consonance and Tanner stages of puberty (5)
everyone goes through each stages - only things that vary: time spent in each stage + time taken to move from one stage to another = consonance -> useful for diagnosing sex disorder
Stage 1: no dev. breast and testis
Stage 2:
Stage 3:
Stage 4:
Stage 5: full dev.
Consonant growth and sexual development milestones (4)
Pubic hair: 2-3-4-5 (13-16 b), (11-13,13-15 g)
Testes/ Breast: 2-3-4-5 (12-15 b), (11-13,13-15 g)
Penis/Menarche: 2-3-4-5 (girls=13yrs)
Growth: 12-16yrs(b), 11-15yrs(g)
Why the fuss about the timing of puberty? (5)
Potential adverse risks from early puberty:
- cardiovascular disease
- metabolic disease
- obesity
- diabetes
- disordered behaviour - sexual maturity before psychological
- decreased adult height - bone fusion earlier
- decreased life expectancy
What controls the onset of puberty? (7)
- Dialogue between our individual genetics + environmental factors
- All impinge at different points of the HPG axis
A number of theories have been put forward:
– Inherent maturation of CNS
– Body fat/nutrition – Leptin and Ghrelin?
– Hypothalamic hormones -Kisspeptin, other factors?
– Latest theories - Epigenetics?
Onset of puberty/menarche trends (2)
-Secular trend to earlier age at menarche in girls from W. Europe & USA » Average age of menarche onset in UK = 12.5yrs
-link b/w energy homeostasis + reproduction
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Nutrition and body fat(5)
- 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
- Frisch et al.: “critical fat mass” hypothesis
-Threshold % fat/body weight is required to attain (17%) and maintain female reproductive ability (22%) -> energy intensive stages = need enough energy to undergo
Cross talk between metabolic status and puberty onset/maintenance of reproduction
Nutritional gating and puberty-gut,adipose,hypo (3)
evidence to show hypothalamus: gut, adipose tissue, gonadal function
communication b/w gut secretions + adipose tissue secretions act on hypo = modulates axis (gonadal function)
Adipose Tissue: Leptin (Mice) (5)
1950’s: ob/ob mouse
* Hyperphagic
* Hyperglycaemic
* Insulin resistant
* Infertile
* Leptin deficient
Adipose Tissue: Leptin (kid) (7)
- 1994: leptin gene cloned
- Expressed in adipocytes-WAT
- Sensor of energy sufficiency
- Satiety factor - tells brain you’re full
- Stimulates energy expenditure
- Circulating levels directly proportional to amount of body fat
- Influence on reproductive system
-ob/ob mice & humans - hypogonadotrophic hypogonadism
-Delayed/absent puberty
-Can be reversed with leptin injection
-Some leptin-deficient patients have normal menses/LH/oestradial levels- unknown why.
