W4 - Hypothalamic-Pituitary-Gonadal Axis II Flashcards
What is Puberty?
- Transition from non-reproductive to reproductive state
- Gonads produce mature gametes:
- Testes -> spermatozoa
- Ovaries -> oocytes (born with full amount for life time. At puberty, gains competence for fertilisation).
- Breast development in females, and increased testicular volume in males.
- Secondary characteristics develop (primary are present at birth)
- Profound physiological changes
- Profound psychological changes
What is Andrenarche (pubarche)?
Caused by secretion of Adrenal androgens.
Growth of pubic
hair, axillary hair
Growth in height
Independently regulated
What is Gonadarche?
LH/FSH
LH - steroid synthesis –> secondary sex characteristics
FSH - growth of testis (male)/steroid synthesis/folliculogenesis (female)
What are the mechanisms behind Adrenarche?
- Change in adrenal androgen secretion due to cellular remodelling of adrenal gland:
- Dehydro-epiandrosterone (DHEA)
- Dehydro-epiandrosterone sulphate (DHEAS)
Gradual increase 6 15 years
20-fold increase peaking at ̴20-25 years
Declines thereafter
No change in other adrenal steroids
* Secreted from zona reticularis of adrenal cortex
* No known mechanism for trigger of adrenarche
What is the Adrenarche:Pubicarche?
This is a consequence of Adrenarche.
* Appearance of pubic / axillary hair resulting from adrenal androgen secretion
- Associated with:
- Increased sebum production = acne
- Infection, abnormal keratinization = acne
- If before 8 years (girls) or 9 years (boys)
= PRECOCIOUS
What is the mechanism behind Gonadarche?
- Several years after adrenarche (typically ~11 yrs of age)
- Reactivation of hypothalamic GnRH
- Activation of gonadal steroid production -> production of viable
gametes and ability to reproduce
What is the relationship of GnRH and Gonadarche?
- GnRH is synthesised & secreted by specialist hypothalamic centres – GnRH neurones.
- HPG axis is first activated at 16th gestational week On the 20th week scan of a baby, you are able to tell the gender because of this.
- Pulsatile GnRH secretion in foetus until 1-2 years postnatally when ceases
- Re-activation at ~11 years
- GnRH neurones ‘restrained’ during postnatal period -> 10 years or more
- At puberty a gradual rise in pulsatile release of GnRH
In studies, LH secretion is used instead of GnRH because they mimic the same function. This is because GnRH is only present in the hypothalamic circulation - can’t get consent from people.
What stimulates the onset of puberty?
Clear that it is maturational event within the CNS
Inherent (genetic) maturation of 800-1000 GnRH synthesising
neurones?
Environmental/genetic factors?
Body fat/nutrition?
Kisspeptin?
How does nutrition and body fat relate to reproduction?
- Link between fat metabolism & reproduction
- Anorexia nervosa / intensive physical training
- Reduced response to GnRH
- ↓gonadotrophin levels
- Amenorrhea
- Restored when nourished / exercise stopped
- Frisch et al.: body fat hypothesis
- Certain % fat:body weight necessary for
menarche (17%) & required (22%) to
maintain female reproductive ability. It makes sense because if you are not at the correct amount of energy reserves, they should not be having a baby.
What is the relationship between nutritional gating and puberty?
There are studies that link Ghrelin, the appetising factor and Leptin, the satiety factor to nutritional gating and puberty. Both of these factors link to the Hypothalamus so they influence the activity of Kisspeptin thus GnRH, which in turn affects the onset of puberty.
What is the relationship between Kisspeptin and puberty?
Inactivating mutations of KISS1R or the gene coding for kisspeptin
* Hypogonadism
* Failure to enter puberty
* Hypogonadotrophic hypogonadism
Activating mutations of KISS1R
* Precocious puberty
What is Consonance?
“Smooth ordered progression of changes”
Order of pubertal changes is uniform
* Age of onset, pace & duration of changes
* Wide inter-individual differences
* Average age of menarche onset (UK) = 12.5 years
For females the onset begins with breast bud and for males with the enlargement of genitals followed by an order of events that leads to full maturity - this order is called consonance.
Studies around the world shows that the onset of puberty begins on average 2 years earlier because we are doing better in terms of nutrition etc globally.
What are the tanner stages of puberty: scale of physical measures of development?
- Pubic and axillary hair growth (♀♂)
- Testicular volume and penile length (♂)
- Breast development (♀)
What are the physical changes in girls during puberty?
- Breasts enlarge: thelarche – first outward sign of E2 activity
- Pubic/axillary hair
- Uterus enlarges, cytology changes, secretions in response to E2
- Uterine tubes
- Vagina
- Cervical changes
- Height: earlier onset than boys, peak height velocity (PHV) = 9 cm/y, reached at 12 yrs
- Body shape
- HPG axis: increase in ovarian size and follicular growth
- Menarche: not equated with onset of fertility
- Fertility: in 1st year ~80% menstrual cycles
anovulatory, irregular cycles
What are the Physical changes in boys during puberty?
- External genitalia
- increase in testicular volume >4 ml
- growth of penis, scrotum, scrotal skin changes
- Vas deferens
- lumen increases
- Seminal vesicles & prostate
- Facial/body hair
- Pubic / axillary hair
- Larynx –
- androgens enlarge larynx, Adams apple (projection of thyroid cartilage), voice deepens
- Height
- PHV =10.3 cm/y reached at 14 yrs
- Body shape
- Onset of fertility
- testosterone from Leydig cells stimulates meiosis & spermatogenesis in Sertoli cells
- boys fertile at the beginning of puberty
