HPG Axis 2 Flashcards
Adrenarche definition:
The first endocrine event of puberty. It is the result of cellular maturation of the adrenal gland, which results in the increase in DHEA/DHEAS production. This usually occurs approximately 6-8 years of age and is independently regulated from gonadarche.
Gonadarche definition:
The second endocrine event of puberty. The ‘re-awakening;’ of the HPG axis, initially presenting as a nocturnal rise in GnRH (measured via LH), and results in the initiation of fertility.
Tanner Stages of Puberty:
Five stage scale of puberty, originally developed by the paediatric endocrinologist, James Tanner. It describes the physical changes in breast development (females), hair development and external genitalia, with the first stage of puberty being breast budding in females, and an increase in testicular volume > 4ml in males.
diagram
Consonance:
The completion of each stage of puberty in the correct order, as denoted by the Tanner Stages of Puberty, known as the ‘smooth ordered progression’. The time that individuals take to go through each stage may differ, but the order in which the stages are completed remains the same between individuals.
Puberty
- Transition from non-reproductive to reproductive state
- Gonads produce mature gametes:
- Testes = spermatozoa
- Ovaries = oocytes
- Breast development in females, and increased testicular volume in males.
- Secondary characteristics develop (primary are present at birth)
- Profound physiological changes
- Profound psychological changes
Two endocrine events of puberty
Adrenarche (pubarche) Adrenal androgens Growth of pubic hair, axillary hair Growth in height Independently regulated
Gonadarche LH/FSH LH - steroid synthesis --> secondary sex characteristics FSH - growth of testis (male)/steroid synthesis/folliculogenesis (female)
Adrenarche explained
• Change in adrenal androgen secretion due to cellular remodelling of adrenal gland.• Dehydro-epiandrosterone (DHEA)
• Dehydro-epiandrosterone sulphate (DHEAS)
Gradual increase 6 15 years
diagram
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
Adrenarche: Pubarche
• 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
Gonadarche Explained
• 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
diagram
Gonadarche: GnRH
• GnRH is synthesised & secreted by specialist hypothalamic centres –
GnRH neurones.
• HPG axis is first activated at 16th gestational week
- 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
diagram
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?
Nutrition & body fat
- 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
Nutritional gating and puberty
diagram
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
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
diagram
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 Physical changes in girls during puberty
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
Growth Spurt
Complex interaction
- Growth hormone
- Oestrogen (boys and girls)
Earlier in girls – approx. 2 years
Biphasic effect of oestrogen on epiphyseal growth
- Low levels = linear growth & bone maturation
- High levels = epiphyseal fusion
diagram
Effects of androgens on the differentiation of pilosebaceous units (PSUs)
diagram
Psychological Changes
- Increasing need for independence
- Increasing sexual awareness/interest
- Development of sexual personality
Later maturation = better adjustment
Precocious sexual development
Development of any secondary sexual characteristic before the age of 8 in girls before the age of 9-10 in boys
Precocious puberty/sexual development
Premature activation of HPG axis
1. Gonadotrophin-dependent (or central) precocious puberty – consonance
– Excess GnRH secretion - idiopathic or secondary
– Excess gonadotrophin secretion - pituitary tumour
- Gonadotrophin-independent precocious puberty - loss of consonance
– Testotoxicosis - activating mutation of LH receptor
– Sex steroid secreting tumour or exogenous steroids
McCune Albright syndrome
mutations in the GNAS1 gene
Café au lait skin pigmentation
Autonomous endocrine function – most common gonadotrophin- independent precocious puberty
hyperactivity of signalling pathways & over-production of hormones
Fibrous dysplasia
diagrams
Pubertal delay def
Absence of secondary sexual maturation by 13yrs in girls (or absence of menarche by 18yr) or 14yrs in boys
