Hypothalamic Pituitary Axis: 2 Flashcards
Define puberty
The transition from non-reproductive to reproductive state
What gametes do the testes and ovaries produce?
- Testes -> spermatozoa (increased testicular volume above 4ml)
- Ovaries -> oocytes (competent for fertilisation) (breast development)
When do secondary characteristics develop?
Secondary characteristics develop (primary are present at birth)
What are the two endocrine events of puberty?
Adrenarche (adrenal androgens) and Gonadarche (LH/FSH)
What results from Adrenarche and Gonadarche?
Are they independently regulated?
Growth of pubic hair and axillary hair. Growth in height
LH - steroid synthesis -> secondary sex characteristsics
FSH - growth of testis (male)/ steroid synthesis/ folliculogensis (females)
They result in puberty, they are independently regulated, you don’t need to have adrenache to have gonadarche and vice versa.
What secretes adrenal androgens in a foetus?
What is the foetal and diffinative zone?
What occurs at birth to these zones?
What happens when this remodelling process is complete?
What 2 steroid hormones change during adrenarche?
Describe them
Remodelling: During foetal development, the adrenal glands in the foetus secretes adrenal androgens, the foetal and diffinative zone – responsible for secretion of androgens during foetal development.
Following birth they under remodelling and shrinking of the foetal zone and the diffantive zone that differentiates into the layers of the adrenal gland that produce adrenal androgens during adrenarche. Once this remodelling is complete you start to have an increase in the secretion of adrenal androgens – DHEA AND DHEAS. Occurs at 6 to 8 start to rise. Increases till age 15 and peaks in mid 20s. It then starts to decline. Only these 2 steroids change during adrenarche
• Dehydro-epiandrosterone (DHEA)
• Dehydro-epiandrosterone sulphate (DHEAS)
Secreted from zona reticularis of adrenal cortex – after remodelling and the differentive zone has differentiated into different layers. This layer produces DHEA AND DHEAS.
No known mechanism for trigger of adrenarche
What is Adrenarche: Pubarche?
What is it associated with
When does it occur (special term used)
• Appearance of pubic / axillary hair resulting from adrenal androgen secretion
• Associated with:
Increase of sebum production = acne
Infection, abnormal keratinization = acne
• If before 8 years (girls) or 9 years (boys)
= PRECOCIOUS (early puberty)
When does Gonadarche occur?
• Several years after adrenarche (typically ~11 yrs of age)
What does Gonadarche cause?
- Reactivation of the HPG axis
- Reactivation of hypothalamic GnRH. We say reactivation because the HPG axis is initially activated during foetal development and shutdown shortly after.
- Activation of gonadal steroid production -> production of viable gametes and ability to reproduce
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When is GnRH synthesised, especially during Gonadarche?
• 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
Describe the levels of GnRH throughout a lifetime
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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?
What is the link between fat metabolism and reproduction?
- Link between fat metabolism & reproduction
- Anorexia nervosa / intensive physical training
a. Reduced response to GnRH
b. ↓gonadotrophin levels
c. Amenorrhea
d. Restored when nourished / exercise stopped - Frisch et al.: body fat hypothesis
a. Certain % fat:body weight necessary for menarche (17%) & required (22%) to maintain female reproductive ability
What does the release of Ghrelin and Leptin cause?
The release of ghrelin and leptin act on the hypothalamus which is involved with the secretion of kisspeptin which affects the release of GnRH which affect the onset of puberty
What does Inactivating mutations of KISS1R or the gene coding for kisspeptin cause?
- Hypogonadism
- Failure to enter puberty
- Hypogonadotrophic hypogonadism
What does Activating mutations of KISS1R – receptor is active resulting in the secretion of GnRH cause?
• Precocious puberty
Define Consonance
“Smooth ordered progression of changes”
• Order of pubertal changes is uniform
Is the age of onset different in males and females?
Yes
What does Tanner stages of puberty describe?
- Pubic and axillary hair growth (♀♂)
- Testicular volume and penile length (♂)
- Breast development (♀)
What are the physical changes that occur in men 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
• Men are fertile as soon as puberty as finished, which is different to females
What are the physical changes that occur in females?
• 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. This means fertility doesn’t kick in till after a year of menarche. As the body is getting used to follicle recruitment and follicle selection.
What causes a growth spurt and what interacts to cause this?
Describe the Biphasic effect of oestrogen on epiphyseal growth
Adrenal androgens do also contribute towards this process.
Complex interaction between:
• Growth hormone
• Oestrogen (boys and girls)
Biphasic effect of oestrogen on epiphyseal growth
• Low levels of oestrogen -> linear growth & bone maturation
• High levels -> epiphyseal fusion – bone fusion marks the end of bone growth
Describe the Effects of androgens on the differentiation of pilosebaceous units (PSUs)
There are 2 main types of pilosebaceous units:
Sebaceous and vellus
- Androgens stimulate sebum secretion and together with infection this can cause acne.
- Androgens can induce differentiation of vellus PSUs to terminal PSUs encouraging mustache and beard growth.
- Androgens can induce differentiation of vellus hairs to apo-PSUs encouraging increased growth in areas of pubic and axillary hair.
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What physiological changes occur during puberty?
- Increasing need for independence
- Increasing sexual awareness/interest
- Development of sexual personality
Later maturation = better adjustment
What is precocious puberty?
Precocious sexual development - Development of any secondary sexual characteristic before the age of 8 in girls and before the age of 9-10 in boys
How might precocious puberty manifest?
- . 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:
Gonads undergo premature maturation and synthesis and secrete steroids at abnormally high rates
• Testotoxicosis - activating mutation of LH receptor. This means the leydig cells produce testosterone, which causes in the enlargement of genitalia.
• Sex steroid secreting tumour or exogenous steroids.
• Results in the enlargement of the genitalia. This is the only change you get within puberty for both of these 2 bullet points
What causes McCune Albright syndrome – e.g Gonadotrophin-independent precocious puberty?
What are the symptoms?
This is caused by mutations in the GNAS1 gene which codes for the G alpha S subunit in the G protein. Therefore all the pathways that rely on G protein pathways are activated, such as Lh Aand FSH. This causes precocious puberty.
You also get (due to the activation of G-protein coupled receptors):
• Café au lait skin pigmentation
• Autonomous endocrine function – most common gonadotrophin- independent precocious puberty
Define pubertal delay
Absence of secondary sexual maturation by 13yrs in girls (or absence of menarche by 18yr) or 14yrs in boys
How might pubertal delay manifest?
- Constitutional delay – prolonging of the prepubertal phase:
• 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)
Reduce gonasterioid production, small gonad structures:
• Kallman’s syndrome (X-linked KAL1 gene, impaired GnRH migration). This migration means the GnRH neurons do not originate in the hypothalamus, they originate in the preoptic region of the nasal region and they migrate to the hypothalamus during fetal development. Regulated by genetic cues and genes, that regulate the migration. If there is a mutation in any of these genes e.g the Kall1 gene, you get impaired migration and have impairment of GnRH function. Results in Hypogonadotrophic hypogonadism
• 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
