Puberty and the HPG axis Flashcards
What is puberty?
- A stage of human development when sexual maturation and growth are completed
- Results in ability to reproduce due to activation of reproductive system
What influences the timing of puberty?
- Pineal gland
- Body weight
- Nutrition - need leptin
- Environment - onset age differs across globe
- Genetics
What is the critical weight for puberty onset?
- 47 kg
At what age does puberty begin in boys?
- 9-14 years
Outline how puberty progresses in boys
- Starts with genital development
- Pubic hair growth
- Spermatogenesis
- Growth spurt
What are male secondary sexual characteristics?
- Increased and thickened hair on trunk, pubis, axillae, and face
- Increased laryngeal size
- Deepening of voice
- Increased bone mass
- Increased muscle mass and strength
When does puberty begin in girls?
- 8-13
Outline how puberty progresses in girls
- Thelarche - breast bud enlargement (8-11)
- Adrenarche - pubic hair growth (11-12)
- Growth spurt (10-14)
- Menarche (11-15)
What are the female secondary sexual characteristics?
- Pubic and axillary hair
- Enlargement of labia minora and majora
- Keratinisation of vaginal mucosa
- Uterine enlargement
- Increased fat in hips and thighs
Compare accelerated somatic growth in boys vs in girls
- Depends on growth hormones in both sexes
- Earlier and shorter in girls
- Boys have longer and faster growth spurt
- Ended in both sexes by epiphyseal fusion
- Oestrogen closes epiphyses earlier in girls
What is the average age for onset of puberty?
- Boys = 12.5
- Girls = 11.5
What is the first sign of puberty?
- Increased testicular volume
- Breast bud development
How does early/late maturation affect boys and girls?
- Early maturation is a positive experience for boys but may be negative for girls
- Late maturation is usually more difficult for boys than for girls
- Adolescents compare themselves to their peers
- Affected by reaction of others to their changing bodies
What is switched on at puberty?
- HPG axis
Which part of the brain regulates the function of the reproductive glands?
- Hypothalamus-pituitary unit
- FSH, LH and prolactin most significant hormones
How do we know the HPG axis is about to be switched on?
- Increased frequency and amplitude of pulsatile GnRH
- Occurs first at night and then progressively throughout day
- Onset of puberty associated with steady rise in LH and FSH
What is GnRH?
- Gonadotrophin releasing hormone
- Produced in neurons of hypothalamus
- Regulates puberty onset, sexual development and ovulatory cycle in females
How does GnRH release differ in men and women?
- In males, pulses 2 hourly
- In females at changes according to phases of menstrual cycle
Why does GnRH have to be released in pulses?
- Continuous release would stop production of LH and FSH because receptors would get desensitised
- Can use high levels of GnRH to delay onset of puberty or treat endometriosis
What affect does GnRH have on the anterior pituitary?
- Stimulates anterior pituitary gland gonadotrophs to secrete LH and FSH
- GnRH reaches anterior pituitary via hypophysial portal system
- Intensity of GnRH stimulus is affected by frequency and intensity of release
What is the important function of LH and FSH in puberty?
- High levels of LH and FSH initiate gonadal development
- Between 9-12 years, blood levels of LH and FSH increase
What is sleep dependent rise in nocturnal LH?
- In adolescent boys there is sleep related LH increase
- Stimulates nocturnal testosterone rise
- Androgen increase could account for some early pubertal changes in males
- Females have similar increase in oestrogen
Outline the HPG axis
- Hypothalamus secretes GnRH
- GnRH causes anterior pituitary to secrete LH and FSH
- FSH stimulates gonads to produce androgens in males or oestrogen in females
-Increased levels of oestrogen/androgens have a negative-feedback effect on hypothalamus
What does FSH stimulate in males?
- Stimulates Sertoli cells
- Spermatogenesis
- Inhibin released - negative feedback on anterior pituitary and possibly hypothalamus
What does LH stimulate in males?
- Leydig cells
- Testosterone released
- Negative feedback on hypothalamus and anterior pituitary
Describe the structure of the seminiferous tubules
- Testes divided into lobules
- Each lobule contains 1-4 tightly coiled seminiferous tubules (~60 cm long)
- Sertoli cells found in seminiferous tubules
- Location for spermatogenesis
- Loose connective tissue and blood vessels found between seminiferous tubules
Where are Leydig cells found in the testes?
- Found in interstitial tissue
- Produce testosterone
- Cells function independently of seminiferous tubules
Which cells line the seminiferous tubules?
- Sertoli cells
- Spermatogenic cells/germ cells
- Makes a complex epithelium
What is the function of the seroli cells?
- Provide nutrition and hormonal support to germ cells allowing sperm formation
- Sensitive to FSH (increase sperm production)
- Secrete inhibin - negative feedback on anterior pituitary and FSH
What is the function of FSH in females?
- Stimulates granulosa cells
- Follicular development
- Release of inhibin - specifically inhibits FSH only
- Granulosa cells convert androgens to oestrogen
What is the function of LH in females?
- Stimulates theca interna cells to release androgens
- These androgens are then converted to oestrogen by granulosa cells
- LH surge required for ovulation
- LH maintains corpus luteum after ovulation
How does oestrogen affect GnRH?
- Moderate titres of oestrogen reduce GnRH secretion
- Negative feedback
- High titres of oestrogen alone promote GnRH secretion
- Positive feedback
- LH surge stimulates ovulation
How does progesterone affect oestrogen and LH/FSH?
- Increases inhibitory effects of moderate oestrogen
- Prevents positive feedback of high oestrogen
- No LH surge
- Increases frequency of GnRH pulses
Which cells release inhibin in the female?
- Granulosa cells
Which hormones lead to a growth spurt?
- Growth hormone
- Increased androgens
- Leptin
What are the effects of growth hormone?
- Secreted by pituitary gland
- Increases TSH
- Increases metabolic growth
- Promotes tissue growth
What are the effects of increased androgens on a growth spurt?
- Retention of minerals in body to support bone and muscle growth
What is leptin?
- Adipocyte-derived protein hormone
- Has a pulsatile release pattern
What is the function of leptin?
- Signals information about energy stores to CNS
- Important role in regulating neuroendocrine function
- Reproductive dysfunction associated with leptin deficiency
- Can accelerate onset of reproductive function
- Can regulate GnRH levels
What is central precocious puberty?
- Precocious puberty with elevated GnRH levels
- Causes premature activation of hypothalamic- pituitary axis
What are the causes of central precocious puberty?
- Idiopathic or constitutional (most cases)
- CNS lesions
- Pituitary gonadotropin secreting tumours (rare)
- Systemic conditions
- Obesity
How is central precocious puberty diagnosed?
- Laboratory tests
- Basal LH and FSH increased
- GnRH stimulation tests
- Serum testosterone/oestrogen increased
What is peripheral precocious puberty?
- Precocious puberty without elevated GnRH levels
What are the causes of peripheral precocious puberty?
- Increased androgen production
- E.g. due to ovarian cyst or congenital adrenal hyperplasia
- Increased oestrogen production
- E.g. due to HCG secreting germ cell tumours
- Increased beta-HCG production e.g. hepatoblastoma
- Primary hypothyroidism
- Obesity-related
What can cause delayed onset of puberty?
- Constitutional growth delay
- Malnutrition
- Chronic diseases e.g. IBD, hypothyroidism
- Hypogonadism
