REPRO: Hypothalamic-Pituitary-Gonadal Axis II Flashcards
Briefly, describe puberty.
Puberty is the transition from the non-reproductive to reproductive state.
The gonads produce mature gametes:
- the testes make spermatozoa
- the ovaries develop oocytes
It can also be (clinically) defined as breast development in females, and increased testicular volume in males.
It’s the secondary characteristics that develop, as the primary ones are present from birth.
There are also some profound physiological changes, such as hair patterning, height, and actual body shape, along with some psychological changes.
What are the two endocrine events that occur during puberty?
- ADRENARCHE (that leads to PUBARCHE)
- growth of pubic and axillary hair
- growth in height. - GONADARCHE
- LH leads to steroid synthesis and the development of secondary characteristics
- FSH stimulates the growth of testes in males and steroid synthesis and follicular genesis in females.
These are both independent to each other.
Describe adrenarche.
It is the change in adrenal androgen secretion due to cellular remodelling of the adrenal.
It is DHEA (dehydroepiandrosterone) and DHEAS (dehydroepiandrosterone sulphate) that change.
There is a gradual increase in their serum levels, starting from the age of 6-15, to a 20-fold increase peaking at 20-25 years of age. It declines thereafter.
It is secreted from the zona reticularis of the adrenal cortex.
There are no known mechanisms for the trigger of adrenarche. There is no change in other adrenal steroids.
Describe pubarche.
It is the appearance of pubic/axillary hair resulting from the adrenal androgen secretion.
It is associated with increased sebum production, which can cause acne. Infection and abnormal keratinisation can also cause acne.
If this occurs before the age of 8 years (girls) or 9 years (boys) - it is due to PRECOCIOUS (early) puberty.
Describe gonadarche.
It occurs several years after adrenarche (typically at around 11 years of age).
It is the reactivation of the hypothalamic-pituitary-gonadal axis (because, during foetal development, the HPG axis is in full working order, as it is required for male differentiation).
It is the activation of gonadal steroid production, leading to the production of viable gametes and ability to reproduce. This is achieved via the HPG pathway.
When is the HPG axis first activated and when does GnRH secretion cease and reactivate?
GnRH is synthesised and secreted by specialist hypothalamic centres - the GnRH neurones.
HPG axis is first activated at the 16th gestational week. - sexual differentiation should occur after this activation, therefore the sex of the foetus can be seen in the week 20 scan.
The pulsatile GnRH secretion in the foetus occurs until 1-2 years postnatally, then it ceases. Reactivation at about 11 years.
The GnRH neurones are ‘restrained’ during this postnatal period, for about 10 years or more.
At puberty, there is a gradual rise in the pulsatile release of GnRH.
What changes in the pattern of LH secretion occur during puberty?
During early to mid-puberty, there is a nocturnal rise of LH secretion, after which the rise normalised throughout the 24 hour period.
LH mimics activity of GnRH and is thus is sampled. (GnRH is in the hypophyseal portal circulation - difficult to sample + ethical consideration).
What stimulates the onset of puberty?
We do not know exactly what causes the onset of puberty.
It’s clear that it is a maturational event within the CNS.
- the inherent (genetic) maturation of 800-1000 GnRH synthesising neurones?
- environmental/genetic factors (research in epigenome)?
- body fat/nutrition?
- kisspeptin (gate keeper of puberty)?
What does nutrition and body fat have to do with puberty?
There is a known link between fat metabolism and reproduction (eg. there is metabolic dysfunction in
Polycystic ovary syndrome (PCOS), a reproductive hormone imbalance syndrome).
Also, in people with anorexia nervosa/ people who undergo physical training, it is found that they have:
- a reduced response to GnRH
- decreased gonadotrophin levels
- amenorrhea
- ^ that is restored when they are nourished/ they stop exercise
Frisch et al - body fat hypothesis:
- Certain percentage of body fat required for menarche (17%) & required (22%) to maintain female reproductive ability.
How does nutritional gating affect the onset of puberty?
Ghrelin (hunger) and Leptin (satiety) hormones act on the hypothalamus. This influences the activity of kisspeptin and GnRH, and thus the onset of puberty.
What do mutations in the KISS1R (kisspeptin receptor) cause?
Inactivating mutations of the KISS1R or the gene coding for kisspeptin can lead to:
- hypogonadism
- failure to enter puberty
- hypogonadotropic hypogonadism
Hypogonadism - condition where the male testes or the female ovaries produce little/no sex hormones. Hypogonadotropic hypogonadism (HH) - form of hypogonadism due to a problem with the pituitary gland or hypothalamus.
Activating mutations of KISS1R (without kisspeptin) lead to:
- precocious puberty
(activate downstream signaling pathways leading to production and secretion of GnRH.)
What is consonance?
Consonance refers to the smooth ordered progression of changes through puberty.
The age of onset, pace and duration of changes are differences that will be large between individuals, but the order that they occur in remains the same.
The average age of menarche onset (in the UK) is 12.5 years, decreased by 2 years over the last 100, and looks to be still decreasing.
Describe the Tanner stages of puberty.
It is a scale of physical measurements of development.
There are 5 stages, and it looks at 3 parameters:
- breasts in females
- pubic and axillary hair growth
- male genitalia in males (testicular volume and penile length.)
Describe the physical changes in girls during puberty.
- breasts enlarge (thelarche, the first outward sign of E2 activity)
- pubic/axillary hair
- uterus enlarges, cytology changes, secretions occur in response to E2
- uterine tubes
- vaginal changes (secrete fluids)
- cervical changes (secrete fluids)
- height (earlier in boys than girls, peak height velocity is reached at age 12)
- body shape (hips widen, etc.)
- HPG axis activation (increase in ovarian size and follicular growth
- menarche (not equated with the onset of fertility)
- fertility (during the first year, around 80% of the menstrual cycles are anovulatory, irregular cycles) –> fertility can occur usually after a year of menarche as the HPG axis is getting used to its new role of follicle recruitment and and dominant follicle selection.
Describe the physical changes in boys during puberty.
- external genitalia (increase in testicular volume, growth of penis, scrotum, scrotal skin changes)
- vas deferens (lumen increases)
- seminal vesicles and prostate (secretions)
- facial/body hair
- pubic/axillary hair
- larynx (androgens cause the enlargements of the larynx, Adam’s apple [projection of thyroid cartilage], voice deepens)
- height (peak height velocity reached at age 14)
- body shape
- onset of fertility (testosterone from the Leydig cells stimulates meiosis and spermatogenesis in Sertoli cells) –> boys fertile at the beginning of puberty.
