Puberty Flashcards
what is puberty?
What external features are present/?
final stage of maturation of HPG axis
External: 2’ sex characteristics appear & growth spurt–> striking sexual dimorphism to mature fertil adults
What is the mini-puberty of infancy?
When does it hapen?
Mini-puberty: 6-8wks
- HPG axis becomes active
- sex steroid levels comparable to those seen in early/mid puberty but w/o external effects
- biological relevance is unkown
What is happening in pre-puberty state?
How do children enter puberty?
long period from mini-puberty to puberty where HPG axis is suppressed
**if this suppression is taken away= HPGa is reactivated–>child enters puberty
What are 5 of the major changes in puberty/HPGaxis?
- ^^activity of adrenal glands–>produce steroids
- ^^ pulsatile GnRH & FSH/LH secretion
- corresponding ^^ in circulating estrogen [females] & test [males]
- mitosis of 1’ spermatogonia [no oogonia changes]
- correlated w/ onset of gamete maturation
What hormonal pulses activate steroid prodxn in gonads?
pulsatile GnRH–> Lh surges–> gonad steroid prodxn
What phenotypic changes occur in puberty?
- axial growth
- growth of 2’ sex organs
- gender & nongender specific hair growth
- central processing alterations due to central pathway remodeling
- prioritizing pathways which have developed and removal of those that havent
- impaired judgement
- vocal cord thickening
- menarche
- libido
What are the 4 stages of sexual changes [similar to Tanner staging]?
Adrenarche: adrenal zona reticularis development–> ^^androstenedione & DHEA prodxn–> pubic hair growth
Thelarche: breast development due to ^^ estrogens
Gonadarche: prodxn of ovarian H’s & mature gametes
Menarche: uterine responses to ovarian H’s
What are the Tanner stages of sexual maturity for boys?
What are the Tanner stages of sexual maturity in females?
What are the tanner stages of sexual maturity of both boys & girl [general]?
When do girls start breast development, menarche, and complete puberty on avg?
When do girls usually reach peak height velocity?
Which ethnicity tends to start puberty earlier?
Breast development avg: 10 yo
Peak Height velocity: 11 yo
Menarche: 12 yo
Completes puberty: 14yo
African Am girls tend to start puberty earlier
When do most boys begin pubertal changes?
When do they reach peak height velocity?
When do they reach strength spurt?
When do they complete puberty?
[all on averages]
pubertal changes begin: 11-12 yo
Peak height velocity: 13-14
Completion of puberty: 15yo
Strength spurt: 15.5yo
What factors can influence age of onset of puberty?
genetics, nutrition [BMI & height], others
**^^BMI/height/weight–>earlier onset of puberty [girls esp.]
How has the age of menarche changed over the past 80 years?
age of onset has decreased or become earlier
[from 16yo and now down closer to 13]
What are the 2 forms of precocious puberty?
gonadotropin dependent & gonadotropin independent precocious puberty
(GDPP & GIPP)
What causes GDPP?
- 80% idiopathic
- 20% CNS related: hypothalamic hamartomas, CNS tumors, cranial irradiation, hydrocephalus, trauma
What causes GIPP in girls?
in boys?
Both?
girls: ovarian cysts or tumors
boys: leydig cell tumors, hCG secreting germ cell tumors [gonads, pineal, liver, retroperitoneum, post. mediastinum,–>all areas of movement prior to coelescence in gonadal ridge]
both: exogenous E= adrenal pathology w/ excess androgen/pit tumors
In general, what will we see in GDPP?
early activation of pulsatile activity of HPGaxis [aka CPP] so all puberty signs are stage matched but occur earlier than expected
- pulsatile GnRH–> ^^LH esp & slightly ^^FSH
- leads to ^^sex steroid output
What is the main differentiating component of GIPP from GDPP?
What would presence of GDPP w/ adrenarche show?
What about ^^bone age >chronological age w/ adrenarche [boys] & thelarche [girls] mean/show?
GIPP exhibits one or two signs of puberty but not all [nnot staged similarly]
-
adrenarche present:
- tumors of adreanl [rare]
- CAH–>MC is 21 hydroxylase deficiency
- ^^DHEA levels & ^^random serum 17OH P
- most kids have normal DHEA levels though
-
bone age>chrono age:
- tumors secrete hCG–> binds LH R–>stimulates sex steroid synthesis
- gonadal tumors–>elevated sex steroids BUT NOT gonadotropins
- exposure to exogenous sex steroid hormones
How does precocious puberty effect growth/bone growth?
What is the overall effect?
PP shows increased levels of E–>converts to estradiol E2
- prepubertal bone plates are extra sensitive to E2
- low levels [kid] of E2 favor pubertal growth spurt
- high levels [adult] cause fusion of epiphysis
**kids with PP are SHORTER than avg **due to early fusion
How do we Dx GDPP vs. GIPP?
How do we test for CPP?
Why do we not measure FSH levels?
- GnRH analog stimulation test:
- ^^Gn induced by test = ** GDPP**
- normal/not induced Gn levels = GIPP
- random LH screening test for CPP
- LH< 0.1 IU/L is prepubertal
- LH> 0.3 IU/L or more is pubertal
- random FSH levels dont descriminate b/w PP & pubertal
How do we Tx GDPP?
Drugs for medical castration
- GnRH agonists [nonpulsatile] or antagonists
- anti-E/anti-androgens
- glucoC’s in the case of CAH
What are some major causes of sexual ambiguity?
mutations in H prodxn, H R’s, or downstream signaling
Hypogonadism
Sex chromosome loss
Mosaic individuals
What is sex [gender] determination dependent on?
- genetic sex: X or Y
- gonadal sex: initiated in the 2nd month of fetal development
- phenotypic sex: fetal & pubertal events which dictate phenotype
What is the default sex [gender]?
Female!!!!
Describe 3 steps of female internal sex organ development [1’]?
- absence of SRY protein = gonadal cortex –>ovary
- absence of testosterone = Wolffian ducts degenerate
- absence of Mullerian inhibitory Hormone [MIH] = Mullerian duct–>fallopian tube, uterus, & upper vagina
Describe 3 steps of internal male sex organ development?
- SRY protein present = medulla of bipotent gonad–>testis
- Anti Mullerian H or MIH present = Mullerian ducts degenerate, leaves Wolffian ducts
- Testosterone present = converts Wolffian duct into seminal vesicle, vas deferens, & epididymis
- DHT controls prostate development seperately
In order to become male, what is needed?
When does it start being produced?
What does it do?
SRY= sex determining region of the Y chromosome
- SRY protein is produced by 10 wks
- binds DNA & upregulates transcription of new genes promoting testes development
When does sexual differentiation begin in the embryo/fetus?
7 weeks!!!!
What/when is the bipotent stage?
weeks 1-6 of fetal development when internal repro organs have potential to develop into male OR female structures
What 4 substances are absolutely necessary for normal male sex organ development?
what does each do or contribute to?
- SRY protein aka TDF [testis determining factor]
- MIH: inhibits mullerian ducts
- Androgens: TESTOSTERONE
- develops wolffian duct into accessory structures
- develops external genitalia
- DHEA: develops penis & prostate
What are external genitalia dependent on?
What would happen if male sex hormones are not present?
gonadal sex!!!
External genitalia would be feminized if male sex H’s absent
What are all sex steroids derived from?
Cholesterol!!!
DIt short cut for remembering steroid synthesizing enzyme deficiencies?
**1st # is a 1 = **HTN
2nd # is 1= masculinization
11b-hydroxy= HTN &masculin
17a-hydroxy = HTN
21ahydroxy= masculin [HoTN actually]
What would cause sex ambiguity in males?
46, XY but with low levels of Testosterone:
- deficiency of Cyp11A = a side chain cleavage enzyme
How could virilization of a female child occur? [2 deficiencies]
CAH in 46XX
-
21a-hydroxylase deficiency= ovaries normal
- ambiguous external genitalia [partial defect]
- female external genitalia [complete defect]
- internal structures normal due to no MIH exposure
-
3B-hydroysteroid DH deficiency = possibly impaired ovaries
- female genitalia
- internal structures normoal due to no MIH exposure
- may go unnoticed until puberty
What is androgen insensitivty syndrome? [AIS]
genetics?
who does it affect?
AIS= mutations in AR that reduce its signaling capacity [partial or severe]
- 46, XY cannot or reduced response to androgens
- X-linked recessive trait
- phenotypical males are affected most?
compare and contrast Complete & incomplete AIS?
What is 5a-reductase deficiency?
how common is it?
who does it affect?
Tx?
What should you classify the child as if have nearly absent 5a-reductase?
RARE
_affects: _ 46, XY: produce testosterone but insufficient conversion to DHT
- normal internal genitalia [testis]
- external genitalia [penis & prostate specifically] fail to develop properly = ambiguous female genitalia
- SURPRISE!! female becomes masculinized w/ puberty [if testes left in]
Tx: orchiectomy & E therapy = feminine
nearly absent 5a-reductase= assume female???
Virilization of a presumed female child at puberty is due to what?
increased testosterone:DHT ratio due to 5a-reductase deficiency
female is actually 46 XY
What are 2 sex chromosome anomalies causing sexual ambiguity?
XO Turner syndrome
XXY Klinefelter Syndrome
Turner syndrome can have which chromosomal variations?
What is this a genetic example of?
What is a common consequence in utero of turners?
TURNER’S
- 46 XX OR 45 XO
- example of **mosaicism= **sex chromos are doled out unevenly b/w dividing cells
- earlier in development this happens the more extreme/complete mosaicism is:
- later= most cells get XX and thus less physical attributes
- earlier= most cells are XO and results in a female w/ Turners
- earlier in development this happens the more extreme/complete mosaicism is:
- example of **mosaicism= **sex chromos are doled out unevenly b/w dividing cells
***similar thing happens with klinefelters syndrome
15% of spontaneous abortions ahve XO karyotype
What are the Sx’s/signs of turner syndrome?
loss of short arm of one X chromo [usually paternal X]–>gonadal dysgenesis & other abnormalities:
- neck webbing
- broad/shield chest
- horseshoe kidneys
- CV abnormalities
- short stature
Describe the hormonal effects of Turners syndrome and its effects on sex organ development
What is Klinefelters syndrome?
What is it a genetic abnormality of?
how many males with these genetic abnormality actually express evidence of disease?
Klinefelters is also an example of mosaicism
Klinefelters= 47, XXY
In XXY individuals not all genes on the second X are suppressed/inactivated: some X genes on the psuedoautosomal region correspond to the Y so that triple expression is thought to contribute to the underlying problems
1/500 males carry genotype, but only 1/1000 manifest phenotype
Describe the hormonal effects of Klinefelters syndrome and how it affects sex organ development
Are there only 2 sexes?
What is the best way to determine if an individual is male or female?
Scientists now say that sex/gender is on a spectrum!
If you want to know someones sex, the most relevant answer may be to ask him/her!
