6. Puberty and the HPG axis Flashcards
What is puberty?
•A stage of human development when sexual maturation and growth are completed and result in ability to reproduce
–Morphological physiological and behavioural development
when are primary sexual characteristics established?
before birth
summarise what happens during puberty
–Accelerated somatic growth
–Maturation of primary sexual characteristics (gonads and genitals)
–Appearance of secondary sexual characteristics (pubic and axillary hair, female breast development, male voice changes,…)
–Menstruation and spermatogenesis begin
What is sexual dimorphism?
causes a distinct difference between male and female sexes
What is the typical age of puberty in boys and girls?
10-14, 9-13
What is the sequence of secondary sexual characteristics in girls?
Thelarche, Pubic hair, Growth spurt, Menarche, Pubic hair, Breast development
Define thelarche.
Refers to ‘breast bud’ development, which is the first sign of puberty in girls
Define menarche.
The onset of menstruation at puberty
define adrenarche
Maturation and increased activity of the adrenal glands prior to puberty. - involved in development of pubic hair
define Gonadarche
activation of reproductive glands by the pituitary hormones FSH and LH
what factors affect onset of puberty?
- The pineal gland is thought to be an important influence on puberty
- Body weight
- nutrition and leptin(released from adipose tissue)
- Onset age differs in different areas of the globe
- Economic factors/disparity may effect onset of puberty
how does disorders of pineal gland affect puberty?
can cause early onset (precocious) puberty.
how does low body weight affect puberty?
cessation of menstruation, even after puberty has
occurred
can the sequence of events of puberty vary?
no
the age at which puberty occurs can vary, however, the sequence of which these changes occur is consistent
what are the sequences of puberty in females and at which ages?
9-13 years;
starts with
• Breast bud (thelarche) (8-11)
• Pubic hair growth (T) (11-12)
- Leads to (adrenarche)
- Growth spurt (10-14)
- Menstrual cycles begin (menarche) (11-15)
- Pubic hair adult - become coarser, with further anatomical spread
- Breasts adult - further growth of breast tissue until adult breast enlargement is reached.
what scale is used to assess stages of puberty in boys and girls?
Tanner scale
what are Primary sexual characteristics
These are the sexual characteristics at birth, i.e. before puberty has begun. This includes the anatomy of the internal and external genitalia.
what are Secondary sexual characteristics
These are the characteristics that develop after puberty; i.e. pubic hair, breast or genital development or enlargement, and menstruation in females.
What is the sequence of secondary sexual characteristics in boys?
Genital development, Pubic hair growth, Spermatogenesis, Growth spurt, Genital enlargement, Pubic hair(coarseness and pattern of pubic hair will change until an adult distribution has occurred.)
Which hormone influences pubic hair growth?
testosterone
Which hormones influences growth spurt?
The levels of oestrogen are important in fusion of the epiphyseal growth plate, which will result in the end of the growth spurt. Growth hormone (GH) has a key role in both boys and girls to cause the growth spurt to occur.
what is The first sign of puberty occurring in boys?
testicular volume enlargement.
Why do boys typically grow taller than girls?
Lower levels of oestrogen, epiphyseal growth plates are slower to close
compare growth spurt in boys and girls
- Depends on growth hormone + IGF-1 & sex steroids in both sexes
- Earlier and shorter in girls
- Men larger because growth spurt longer and slightly faster
- Genital development in boys depends on testosterone
- Ended in both sexes by epiphyseal fusion
- Oestrogen closes epiphyses earlier in girls
What is precocious puberty and how does this affect height?
Early onset puberty, can lead to levels of oestrogen
rising earlier, and can therefore result in short stature
Which hormone triggers puberty, where is it produced and where does it act?
GnRH produced in hypothalamus and acts on anterior pituitary.
What 2 stimuli are thought to have an impact on initial GnRH release?
Leptin
What type of secretion does GnRH have?
- Secretion in pulses tied to internal biological clock
- Synchronized external signals i.e. by light
- Nocturnal GnRH pulsatility (LH secretion) precedes phenotypic changes by several years
What does GnRH stimulate in the anterior pituitary?
Release of stored hormones and synthesis of more. Also stimulates hypertrophy and hyperplasia of target cells
Which neoplasia produces ectopic Human Chorionic Gonadotropin and what does this lead to?
Pineal tumours, HCG acts as LH and causes testosterone production in boys leading to precocious puberty
what does GnRH regulate?
puberty onset, sexual development, and ovulatory cycles in females.
what is the location of the GnRH receptor and what type of receptor is it?
anterior pituitary and belongs to the family of the G protein-coupled receptors. (7-TM receptors).
•These receptors, when bound by an activating subunit, undergo conformation change and activate intracellular pathways leading to modulation of genes within a target cell, via phosphorylation events
Which gene is responsible for GnRH production and where is it expressed?
GnRH -1 gene, exclusively expressed in a discrete population of neurons in the hypothalamus
Which blood vessel connects the anterior pituitary to the hypothalamus?
Superior hypophyseal artery
administration of artificial GnRH must be what in nature?
MUST be pulsate in nature - constant administration can lead to decrease in FSH and LH leading to infertility
What hormones are produced in the AP?
- prolactin
- growth hormone (GH)
- thyroid stimulating hormone (TSH)
- adrenocorticotropic hormone (ACTH)
- FSH and LH
Which hormones does GnRH stimulate release of?
- follicle-stimulating hormone (FSH)
* luteinizing hormone (LH)
What type of hormone is GnRH?
peptide hormone, 10 aa
What is the intensity of GnRH stimulus on the AP affected by?
Frequency of release and Intensity of release
How often is GnRH released?
GnRH release is pulsatile
• Every 1-3 hrs
how does the GnRH travel to AP?
GnRH travels to pituitary in hypophysial portal system
what are the effects of LH and FSH?
FSH and LH stimulate the gonads (ovaries or testes) to release androgens and oestrogen. These hormones then drive the physical changes in secondary sexual characteristics that are visible at puberty.
what are the FSH and LH levels like in children, at what age does it begin to change?
- In young children, LH and FSH levels are insufficient to initiate gonadal function
- Between 9-12 yrs., blood levels of LH, FSH increase
- Amplitude of pulses increases, especially during sleep
- High levels of LH, FSH initiate gonadal development
Which cells does LH stimulate in testes and what do these produce?
Leydig cells which produce testosterone
When is testosterone levels the highest?
Morning
Which cells does FSH stimulate in testes and what do these produce?
Sertoli cells, increase sperm production
Which cells in the testes produce inhibin and what is its function?
Sertoli cells, provide negative feedback on anterior pituitary and inhibit production of FSH
Which cells does LH and FSH stimulate in ovaries?
Granulosa cells respond to FSH
Theca cells respond to LH
Which cells in the ovaries produce inhibin and what is its function?
Granulosa cells in corpus luteum, provide negative feedback on anterior pituitary and inhibit production of FSH
–Has a small inhibitory effect on LH
what is the function of inhibin?
pecifically causes negative feedback on FSH only to
prevent further sperm production or maturation of any more follicles.
describe the sleep dependent rise in nocturnal LH
- In adolescent boys the sleep related LH increase
- Stimulates a nocturnal rise of Testosterone
- Androgen levels increase could account for some of the early pubertal changes seen in males
- Similar pattern seen in females with concomitant increase in oestrogen
describe the negative feedback mechanism of HPG axis
release of GnRH from hypothalamus stimulates FSH and LH release from anterior pituitary gland which stimulates gonad to release androgens or oestrogen. the androgens and oestrogen feedback to the hypothalamus to decrease GnRH release
what are seminiferous tubules lined by?
•Lined by complex epithelium made of 2 cell types
–Supporting cells (Sertoli cells)
–Spermatogenic cells/germ cells
what is the functionof sertoli cells, what are they sensitive to and what do they secrete?
–provide nutrition and hormonal support to germ cells allowing sperm formation
–Sensitive to FSH (increase sperm production)
–Secreted inhibin (-) feedback on AP FSH
what does testosterone feedback to?
hypothalamus and anterior pituitary gland
what is the effect of theca cells being stimulated by LH?
–Releases androgens. Converted to oestrogen by
granulosa cells
–LH surge is required for ovulation
–LH maintains corpus luteum after ovulation. Releases
progesterone and oestrogen. Lasts 12-14 days unless
further stimulated by pregnancy hormone betahCG(released after implantation)
what is the effect of granulosa cells being stimulated by FSH?
•Follicular development
–Releases inhibin. Specifically inhibits FSH only
–Granulosa cells convert androgens to oestrogen
what does progesterone and oestrogen feedback to?
hypothalamus and anterior pituitary gland
What effect does moderate levels of oestrogen have on GnRH secretion?
Reduce GnRH secretion by negative feedback
What effect does high levels of oestrogen have on GnRH secretion?
High levels of oestrogen alone promote GnRH secretion by positive feedback leading to LH surge
What is the effect of progestrogen on feedback of oestrogen at moderate and high levels?
–Progesterone increases inhibitory effects of moderate oestrogen
–Progesterone prevents positive feedback of high oestrogen
•No LH surge
how does progesterone and oestrogen result in negative feedback?
Oestrogen reduces GnRH per pulse, progesterone frequency of pulses
summarise the hormones involved in puberty
GnRH –> FSH/LH –> gonadarche –> testosterone/oestrogen –> secondary sexual characteristics
CRH –> ACTH –> adrenarche –> adrenal androgens –> secondary sexual characteristics
GRH –> GH –(+ testosterone/oestrogen) –> growth spurt
describe the changes that lead to growth spurt
Growth Hormone secretion from pituitary •Increases TSH •Increases metabolic rate •Promotes tissue growth •Increased androgens = retention of minerals in body to support bone and muscle growth All leads to growth spurt
What is leptin?
Leptin is an adipocyte-derived protein hormone
What signals does leptin provide to the CNS?
Information about energy stores
what is the effect of leptin on reproductive function?
- important role in regulating neuroendocrine function.
- reproductive dysfunction associated with leptin deficiency
- leptin can accelerate the onset of reproductive function
what is precocious puberty?
Early onset puberty
what is Central precocious puberty
precocious puberty with elevated GnRH levels
what are the causes of central precocious puberty
–Idiopathic or constitutional (most cases)
–CNS lesions
–Pituitary gonadotropin-secreting tumors (rare)
–Systemic conditions: tuberous sclerosis, neurofibromatosis
–Obesity-related precocious sexual development due to increased levels of leptin in obesity
what is the pathophysiology of central precocious puberty?
premature activation of the hypothalamo-hypophyseal axis → abnormally early initiation of pubertal changes → early development of secondary sexual characteristics and gonadarche
how is central precocious puberty diagnosed?
LH and FSH: increased –GnRH stimulation test (gold standard): Gonadotropin (LH und FSH) levels increase after intravenous administration of GnRH. –Sex hormones •♂: ↑ serum testosterone •♀: ↑ serum oestrogen
what is Peripheral precocious puberty?
precocious puberty without elevated GnRH levels
what are the causes of peripheral precocious puberty
–↑ Androgen production, e.g.: •Ovarian cyst (most common cause) •Congenital adrenal hyperplasia •Virilizing ovarian and adrenocortical tumors •Leydig-cell tumor
–↑ oestrogen production, e.g.:
•HCG-secreting germ cell tumors (e.g., granulosa cell tumor)
•Rarely: adrenal gland tumors that produce oestrogen
•McCune-Albright syndrome
–↑ β-HCG production: e.g., hepatoblastoma
–Primary hypothyroidism
–Obesity-related precocious sexual development due to compensatory hyperinsulinemia (caused by increased insulin resistance in obesity)
how is peripheral precocious puberty diagnosed?
Laboratory tests – Increased oestrogen or testosterone, decreased LH and FSH (GnRH
suppressed by elevated gonadal hormones)
define Delayed onset of puberty
absent or incomplete development of secondary sex characteristics by the age of 14 in boys or 13 in girls
what are the 3 causes of delayed onset puberty?
- Constitutional growth delay (most common cause of delayed puberty)
- Malnutrition and other chronic diseases (such as inflammatory bowel disease, hypothyroidism, or psychosocial deprivation)
- Hypogonadism
what is the definition of Constitutional growth delay ?
a temporary delay in growth and onset of puberty that is not caused by any pathological process
what is the eitology of Constitutional growth delay
may be inherited as an autosomal dominant, recessive, or X-linked trait
what is the diagnosis of Constitutional growth delay
: X-ray showing a bone age that is less than the individual’s chronological age
what is the treatment of Constitutional growth delay
No treatment is needed, as catch-up growth eventually occurs and the individual reaches a normal adult height
what initiates puberty and what is the onset associated with?
• Puberty initiated by the brain (HPG axis)
• Onset of puberty associate with steady rise in
FSH & LH secretion
