Describe the basic events that occur with the gonads during gestation
Early in gestation germ cell migration begins and sertoli and Leydig cells begin to be produced from a gonad. Sertoli cells form seminiferous tubes and secrete AMH to cause regression of Mullerian ducts, while Leydig cells are stimulated by placental hCG and secrete testosterone and INSL3. By week 11 all testicular components are present, sertoli cell masses continue to increase, and the testicles descend to the inguinal ring at 14 weeks and then to the scrotum at 35 weeks.
What is the minipuberty experienced by newborns?
There is a rapid rise in testosterone up to 400nd/dL in the first day of life that declines rapidly during the first week to 20-50, then increases over the first 2 months postnatally (this occurs due to transient activation of the HPG axis before CNS inhibition is fully mature). The levels then decline again to prepubertal levels by 1 yr.
During this minipuberty, FSH levels are higher than LH and penile length increases
What are some factors that suppress GnRH pulsatile release after the minipuberty until puberty?
What is Kisspeptin?
A protein believed to be responsible for allowing pulsatile release of GnRH for the onset of puberty. This protein binds to GPR54 receptors on the GnRH neuron body to allow release from the axonal body.
Other stimulatory molecules include leptin, glutamate, and norepinephrine
T or F. GPR54 (the receptor for kisspeptin) is sensitive to GnRH antagonists
T. So it will be turned off as well
NOTE: GPR54 and kisspeptin have increased expression at the time of puberty (maximal expression)
Puberty is marked by the increase in the pulse frequency and amplitude of GnRH, increase in FSH and LH pulses, and rise in gonadal hormones
What neurotransmitters stimulate the HPG axis at the onset of puberty? Inhibit?
Stimulate- GlutamateInhibit- GABA
T or F. Changes in expression of tumor suppressor genes like Oct-2, EAP-1, TTF-1 are permissive for puberty onset
What is Williams Sydrome?
Deletion of 7q11.23 results in normal onset of puberty with rapid progression (point: Genes contiguous with elastin affect pace of puberty)
Signaling through which parts of the hypothalamus are inhibitory to the onset of puberty? Stimulatory?
–Inhibitory tracts appear routed through the posterior hypothalamus
–Stimulatory tracts appear routed through the anterior hypothalamic preoptic area
What is Anosmia?
lack of normal sense of smell
What are some genes that when upregulated inhibit the release of GnRH and the onset of puberty?
What does mutation in KAL-1 cause?
Clinically, mutation results in the X-linked form of Kallmann syndrome. Individuals with Kallmann syndrome experience anosmia (lack of smell) and do not go through puberty (hypothalamic hypogonadotropic hypogonadism).
How is leptin involved in puberty control?
Leptin is secreted by fat cells and in addition to increasing insulin sesnitivity and satiety, acts on the hypothalamus to stimulate GnRH secretion. Thus, deficiency (commonly in very athletic young females with low body fat) can delay puberty. Similarly, prolonged excess of leptin in obese children down regulates GnRH release so delayed puberty can be seen in fat children as well
The HPG axis reaches its nadir at what age?
around 6 years old. Even during the mini=puberty, when there is incomplete suppression of the axis, LH/FSH levels are still very low and it is extremely rare to see sexual development
What is the earliest change seen in late preadolescence before the onset of puberty?
Earliest change is rise in DHEA-S from adrenals
What are some other changes that occur in late preadolescence?
•There is change in amplitude and then frequency of discharge of the GnRH pulse generator
•Results in a sleep-related increase in LH
•Overall there is a 25 fold rise in LH over the course of pubertal development
•LH response is more robust than the FSH response to GnRH and the LH:FSH ratio increases on stimulation
What is a stadiometer?
height measurement device (measure 3x and take an average)
Rules: shoes off, heels together, legs straight, dick out
What is an orchidometer?
Measures testicular size using beads ranging in size
What is the earliest sign of puberty in males?
enlargement of the testes to 4mm
How much of human height is based on genetics?
What is the eqn for midparental height (genetic growth potential) in boys?
•MPH = [father Ht + (mother Ht + 13)]/2 (centimeters)
•MPH = [father Ht + (mother Ht + 5.07)]/2 (inches)
•Average height velocity examples:
–Age 3: ~8 cm/year
–Age 10: ~5 cm/year
–Peak of pubertal growth spurt: ~10 cm/year
What is the eqn for midparental height (genetic growth potential) in girls?
•MPH = [(father Ht-13) + mother]/2 (centimeters)
•MPH = [(father Ht-5.07) + mother]/2 (inches)
T or F. The minpuberty of infancy typically does not have testicular enlargement
Tanner 2 PH
mean lower limit
Caucasian 12y 9y
African Am 11.2y 8y
Mexican Am 12.3y 9.5y
What is constitutional delay?
AD disorder more common in boys in which the age of onset of puberty is delayed by an average of 2.5 years in girls and 3 years in boys
In this variant of normal growth, linear growth velocity and weight gain slows beginning as young as age 3–6 months, resulting in downward crossing of growth percentiles, which often continues until age 2–3 years. At that time, growth resumes at a normal rate, and these children grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years.
At the expected time of puberty, the height of children with CDGP begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt. Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, resulting in normal adult stature and sexual development. Although CDGP is a variant of normal growth rather than a disorder, delays in growth and sexual development may contribute to psychological difficulties, warranting treatment for some individuals. Recent studies have suggested that referral bias is largely responsible for the impression that normal short stature per se is a cause of psychosocial problems; nonreferred children with short stature do not differ from those with more normal stature in school performance or socialization.