Physiology of Puberty Flashcards
Two processes that contribute to the physical manifestations of puberty:
- adrenarche
- gonadarche
Adrenarche
•Adrenarche results in increased adrenal androgen secretion from the zona reticularis. Usually occurs between the age of 6 and 8 years. It is accompanied by changes in pilosebaceous units; associated with transient growth spurt; appearance of axillary and pubic hair in some children; only occurs in humans and some primates.
Gonadarche
•Gonadarche occurs from the activation of the hypothalamic-pituitary-gonadal axis, resulting in true puberty. The hypothalamus secretes pulsatile GnRH, which causes pulsatile secretion of LH and FSH from the pituitary, which causes the gonads to secrete sex steroids. Before puberty, the feedback system is very sensitive, meaning small amounts of sex steroids are enough to inhibit gonadotropin secretion. With the onset of puberty, the sensitivity decreases, which means higher and higher levels of sex steroids are needed to cause inhibition. This decreased sensitivity leads to increased gonadotropin secretion and increased estrogen or testosterone secretion.
How puberty begins…
- How puberty begins: certain neurons in the hypothalamus release a protein called kisspeptin. The kisspeptin binds to gpr54 receptors on other neurons in the hypothalamus which cause release of GnRH. GnRH is carried to the anterior pituitary, which produces LH and FSH secretion. LH and FSH stimulate testosterone production in the testes or estrogen production in the ovaries.
- Exactly what triggers kisspeptin release is unknown, but the cells seem to be influenced by factors such as nutrition and stress.
- Leptin is a hormone produced in adipose cells that suppresses appetite. Circulating leptin levels reflect total body fat. Leptin increases in girls during puberty associated with increases in body fat. Leptin decreases in boys during puberty associated with increased lean body mass and decreased fat mass. Leptin isn’t a trigger for puberty, it has a permissive role, meaning you have to have certain levels of body fat to allow puberty to proceed, but it doesn’t initiate puberty.
- Gonadotropin-Releasing Hormone stimulation test is an important method to tell clinically if someone is in puberty. Pulsatile GnRH is necessary to stimulate the pituitary to cause pulsatile LH and FSH. A pre-pubertal child’s pituitary has not been exposed to pulsative GnRH and will not respond to exogenous GnRH with increased LH. With the initiation of puberty, pulsatile GnRH is released, stimulating the pituitary. This pituitary is thus primed to GnRH; therefore, when exogenous GnRH is administered, the pituitary is able to release LH in response. During adolescence, the LH response to GnRH increases progressively in both sexes. The increase of FSH is much less marked than that of LH.
The first hormonal change associated with the beginning of puberty is [], which eventually leads to increased sex steroids. As puberty progresses, LH pulses increase throughout the day, leading to increased testosterone in boys and estrogen in girls.
•The first hormonal change associated with the beginning of puberty is nocturnal secretion of LH, which eventually leads to increased sex steroids. As puberty progresses, LH pulses increase throughout the day, leading to increased testosterone in boys and estrogen in girls.
Menarche (the first menstrual period) typically occurs about [] after thelarche (beginning of breast development). It is common to have irregular periods for the first couple years after menarche, but usually within 5 years of age, more than 90% of menstrual periods should be ovulatory.
Menarche (the first menstrual period) typically occurs about two years after thelarche (beginning of breast development). It is common to have irregular periods for the first couple years after menarche, but usually within 5 years of age, more than 90% of menstrual periods should be ovulatory.
Order of Pubertal Changes
Disorders of Puberty
Include early puberty or delayed puberty.
- Normal range for beginning puberty in girls: 8-13 years.
- Normal range for beginning puberty in boys: 9-14 years.
- Pubertal changes before the age of 8 years in girls or 9 years of age in boys would be considered early and warrant an investigation. If there are no signs of puberty by the age of 13 years in girls or 14 years in boys, then an evaluation would be needed.
Precocious Puberty
- Precocious puberty is fairly common. It affects one child in 5000 to 10,000. It is idiopathic in 80% of girls. However, in about 2/3 of boys, there is a CNS abnormality.
- Classification of Precocious Puberty: Central precocious puberty, peripheral precocious puberty, combined precocious puberty, variations of normal pubertal development, and contrasexual pubertal development.
Causes of Central Precocious Puberty
Gonadotropin-dependent (central)
- Idiopathic (girls)
- CNS abnormality (e.g. tumor, other)
- Primary Hypothyroidism - van Wyck-Grumbach syndrome: elevated TSH (same alpha subunit as FSH, LH,and hCG) –> gonadal stimulation
- HCG producing tumor (boys)
Causes of Peripheral Precocious Puberty
Girls
- Ovarian Cyst
- Ovarian Tumor
- Adrenal Tumor
- McCune-Albright syndrome
Boys
- Congenital adrenal hyperplasia
- Familial male-limited precocious puberty (testotoxicosis)
- Testicular (leydig cell tumor)
Variations of Pubertal Development: Premature Thelarche
- Usually appears in girls before the age of 3-4 years; typically lasts a couple of years; timing of real puberty is normal otherwise. May notice a little estrogen effect, but nothing significant; no other signs of puberty.
- Premature thelarche may occur in those girls who secrete FSH longer than average or in whom the breast primordia is more sensitive to the small levels of estrogen present in prepubertal girls.
Variations of Pubertal Development: Premature Adrenarche
- Clinical signs of male androgen production (pubic hair, body odor, acne) without signs of true puberty (no penis enlargement, testis or breast development). Plasma DHEA-sulfate is early pubertal and GnRH test is pre-pubertal.
- Premature adrenarche has been associated with an increased risk of insulin resistance in the future.
Delayed Puberty
•Girls without any sign of puberty by the age 13 years or boys without sign by age 14 years. Potential etiologies include: chronic illness, poor weight gain, endocrine disease, thyroid deficiency, interference with the hypothalamic-pituitary-gonadal axis. It is also important to follow the tempo of puberty. Those who start puberty earlier will often take longer to progress through. If puberty progresses too quickly or not quickly enough, it may need to be evaluated.
DDX of Delayed Puberty
- Elevated gonadotropins indicate a primary problem with the gonads. It is often difficult to distinguish permanent hypogonadotropic hypogonadism from constitutional delay.
- Look for features of sundromes such as Turner or Klinefelter which are associated with pubertal delay.
- Kallmans syndrome is hypogonadotropic hypogonadism associated with anosmia.
