HPG axis 2 Flashcards
what do gonads produce?
mature gametes
what do testes produces?
spermatozoa
what do ovaries produce?
oocytes
what is puberty?
the transition from a non-reproductive to a reproductive state
- breast development in females, increased testicular volume in males.
- secondary characteristics develop
- profound physiological changes
do both secondary and primary sexual characteristics develop in puberty?
no, primary are present at birth
what are the 2 endocrine events of puberty?
adrenarche and gonadarche
what is adrenarche?
change in adrenal androgen secretion due to cellular remodelling of adrenal gland
- secretion of DHEA and DHEAS from the zona retucularis
- no known trigger
what is pubarche?
the result of adrenarche
-appearance of pubic / axillary hair resulting from adrenal androgen secretion
what is pubarche associated with?
acne, due to increased sebum production
when does gonadarche occur?
Several years after adrenarche (typically ~11 yrs of age)
what is gonadarche?
- Reactivation of hypothalamic GnRH
- Activation of gonadal steroid production production of viable gametes and ability to reproduce
when does GnRH secretion occur in puberty?
- Pulsatile GnRH secretion in foetus until 1-2 years postnatally when ceases
- GnRH neurones ‘restrained’ during postnatal period, 10 years or more
- Re-activation at ~11 years
- At puberty a gradual rise in pulsatile release of GnRH
there is a nocturnal rise in which hormone?
GnRH
what happens with anorexia nervosa or intensive physical training?
- Reduced response to GnRH
- ↓gonadotrophin levels
- Amenorrhea
- Restored when nourished / exercise stopped
what is required for menarche (first occurrence of menstruation)?
a certain fat body weight
types of KISS1R mutations?
inactivating and activating mutations
what do inactivating mutations of KISS1R cause?
- Hypogonadism
- Failure to enter puberty
- Hypogonadotrophic hypogonadism
Hypogonadotrophic hypogonadism
No GnRH being released, so no LH or FSH aren’t being released, resulting in a hypogonadotrophic status. No positive drive to testis or ovary to produce follicles or mature sperm.
what do activating mutations of KISS1R cause?
overactive receptor that acts in the absence of a ligand
-precocious puberty (puberty occurs early)
what do ghrelin and leptin regulate?
kisspeptin production
what is consonance?
- smooth ordered progression of changes
- puberty follows specific order of changes, individual will always follow this pattern regardless of how long it takes
physical changes in girls during puberty
- Breasts enlarge
- Pubic/axillary hair
- Uterus enlarges, secretions in response to E2
- Uterine tubes
- Vagina
- Cervical changes
- Height
- Body shape
- HPG axis, increase in ovarian size and follicular growth
- Menarche
- Fertility
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 & prostate
- Facial/body hair
- Pubic / axillary hair
- Larynx, androgens enlarge larynx, Adams apple, voice deepens
- Height
- Body shape
- Onset of fertility
what is the Adams apple?
projection of thyroid cartilage
what does testosterone from Leydig cells stimulate in puberty?
stimulates meiosis & spermatogenesis in Sertoli cells
are boys fertile at the beginning of puberty?
yes
what is involved in a growth spurt?
a complex interaction between growth hormone and oestrogen
-earlier in girls
what effect does oestrogen have on epiphyseal growth?
a biphasic effect
- Low levels = linear growth & bone maturation
- High levels = epiphyseal fusion
Psychological changes in puberty?
- Increasing need for independence
- Increasing sexual awareness/interest
- Development of sexual personality
precocious puberty
Development of any secondary sexual characteristic before the age of 8 in girls and 9-10 in boys
premature activation of HPG axis
- Gonadotrophin-dependent 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
what is the most common gonadotrophin independent precocious puberty?
McCune Albright syndrome
what is McCune Albright syndrome?
café au lait skin pigmentation
- g alpha s subunit mutation, activates LH and FSH pathways
- GNAS1 gene mutations
- also side effects because of other hormone pathways being activated
what is pubertal delay?
-absence of secondary sexual maturation by 13yrs in girls or 14yrs in boys
OR
-absence of menarche by 18yrs
give 3 reasons for delayed HPG axis activation?
- Constitutional delay
affecting both growth and puberty. Approx. 90% of all pubertal delay cases.
~10X more common in boys
secondary to chronic illness e.g., diabetes, cystic fibrosis. - Hypogonadotrophic hypogonadism (low LH and FSH)
Kallman’s syndrome (X-linked KAL1 gene, impaired GnRH migration),
Other mutations causing defects in GnRH production - Hypergonadotrophic hypogonadism (high LH and FSH)
Gonadal dysgenesis and low sex steroid levels:
gonadal dysgenesis with normal karyotype, viral e.g. mumps
kleinfelters syndrome genotype
XXY
turners syndrome genotype
XO
- ovarian streak (underdeveloped)
- being shorter than normal
