Puberty

Question 1

what is puberty?

What external features are present/?

Answer 1

final stage of maturation of HPG axis

External: 2’ sex characteristics appear & growth spurt–> striking sexual dimorphism to mature fertil adults

Question 2

What is the mini-puberty of infancy?

When does it hapen?

Answer 2

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

Question 3

What is happening in pre-puberty state?

How do children enter puberty?

Answer 3

long period from mini-puberty to puberty where HPG axis is suppressed

**if this suppression is taken away= HPGa is reactivated–>child enters puberty

Question 4

What are 5 of the major changes in puberty/HPGaxis?

Answer 4

1. ^^activity of adrenal glands–>produce steroids
2. ^^ pulsatile GnRH & FSH/LH secretion
3. corresponding ^^ in circulating estrogen [females] & test [males]
4. mitosis of 1’ spermatogonia [no oogonia changes]
5. correlated w/ onset of gamete maturation

Question 5

What hormonal pulses activate steroid prodxn in gonads?

Answer 5

pulsatile GnRH–> Lh surges–> gonad steroid prodxn

Question 6

What phenotypic changes occur in puberty?

Answer 6

• 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

Question 7

What are the 4 stages of sexual changes [similar to Tanner staging]?

Answer 7

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

Question 8

What are the Tanner stages of sexual maturity for boys?

Answer 8

Question 9

What are the Tanner stages of sexual maturity in females?

Answer 9

Question 10

What are the tanner stages of sexual maturity of both boys & girl [general]?

Answer 10

Question 11

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?

Answer 11

Breast development avg: 10 yo

Peak Height velocity: 11 yo

Menarche: 12 yo

Completes puberty: 14yo

African Am girls tend to start puberty earlier

Question 12

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]

Answer 12

pubertal changes begin: 11-12 yo

Peak height velocity: 13-14

Completion of puberty: 15yo

Strength spurt: 15.5yo

Question 13

What factors can influence age of onset of puberty?

Answer 13

genetics, nutrition [BMI & height], others

**^^BMI/height/weight–>earlier onset of puberty [girls esp.]

Question 14

How has the age of menarche changed over the past 80 years?

Answer 14

age of onset has decreased or become earlier

[from 16yo and now down closer to 13]

Question 15

What are the 2 forms of precocious puberty?

Answer 15

gonadotropin dependent & gonadotropin independent precocious puberty

(GDPP & GIPP)

Question 16

What causes GDPP?

Answer 16

• 80% idiopathic
• 20% CNS related: hypothalamic hamartomas, CNS tumors, cranial irradiation, hydrocephalus, trauma

Question 17

What causes GIPP in girls?

in boys?

Both?

Answer 17

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

Question 18

In general, what will we see in GDPP?

Answer 18

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

Question 19

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?

Answer 19

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

Question 20

How does precocious puberty effect growth/bone growth?

What is the overall effect?

Answer 20

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

Question 21

How do we Dx GDPP vs. GIPP?

How do we test for CPP?

Why do we not measure FSH levels?

Answer 21

• 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

Question 22

How do we Tx GDPP?

Answer 22

Drugs for medical castration

• GnRH agonists [nonpulsatile] or antagonists
• anti-E/anti-androgens
• glucoC’s in the case of CAH

Question 23

What are some major causes of sexual ambiguity?

Answer 23

mutations in H prodxn, H R’s, or downstream signaling

Hypogonadism

Sex chromosome loss

Mosaic individuals

Question 24

What is sex [gender] determination dependent on?

Answer 24

• genetic sex: X or Y
• gonadal sex: initiated in the 2nd month of fetal development
• phenotypic sex: fetal & pubertal events which dictate phenotype

Question 25

What is the default sex [gender]?

Answer 25

Female!!!!

Question 26

Describe 3 steps of female internal sex organ development [1']?

Answer 26

1. absence of SRY protein = gonadal cortex --\>ovary 2. absence of testosterone = Wolffian ducts degenerate 3. absence of Mullerian inhibitory Hormone [MIH] = Mullerian duct--\>fallopian tube, uterus, & upper vagina

Question 27

Describe 3 steps of internal male sex organ development?

Answer 27

1. SRY protein present = medulla of bipotent gonad--\>testis 2. Anti Mullerian H or MIH present = Mullerian ducts degenerate, leaves Wolffian ducts 3. Testosterone present = converts Wolffian duct into seminal vesicle, vas deferens, & epididymis * DHT controls prostate development seperately

Question 28

In order to become male, what is needed? When does it start being produced? What does it do?

Answer 28

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

Question 29

When does sexual differentiation begin in the embryo/fetus?

Answer 29

7 weeks!!!!

Question 30

What/when is the bipotent stage?

Answer 30

weeks 1-6 of fetal development when internal repro organs have potential to develop into male OR female structures

Question 31

What 4 substances are absolutely necessary for normal male sex organ development? what does each do or contribute to?

Answer 31

1. SRY protein aka TDF [testis determining factor] 2. MIH: inhibits mullerian ducts 3. Androgens: TESTOSTERONE * develops wolffian duct into accessory structures * develops external genitalia 4. DHEA: develops penis & prostate

Question 32

What are external genitalia dependent on? What would happen if male sex hormones are not present?

Answer 32

gonadal sex!!! External genitalia would be **feminized** if male sex H's absent

Question 33

What are all sex steroids derived from?

Answer 33

Cholesterol!!!

Question 34

DIt short cut for remembering steroid synthesizing enzyme deficiencies?

Answer 34

**1st # is a 1 = **HTN **2nd # is 1**= masculinization 11b-hydroxy= HTN &masculin 17a-hydroxy = HTN 21ahydroxy= masculin [HoTN actually]

Question 35

What would cause sex ambiguity in males?

Answer 35

46, XY but with low levels of Testosterone: * deficiency of Cyp11A = a side chain cleavage enzyme

Question 36

How could virilization of a female child occur? [2 deficiencies]

Answer 36

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*

Question 37

What is androgen insensitivty syndrome? [AIS] genetics? who does it affect?

Answer 37

**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?

Question 38

compare and contrast Complete & incomplete AIS?

Answer 38

Question 39

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?

Answer 39

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???**

Question 40

Virilization of a presumed female child at puberty is due to what?

Answer 40

**increased testosterone:DHT** ratio due to 5a-reductase deficiency female is actually 46 XY

Question 41

What are 2 sex chromosome anomalies causing sexual ambiguity?

Answer 41

XO Turner syndrome XXY Klinefelter Syndrome

Question 42

Turner syndrome can have which chromosomal variations? What is this a genetic example of? What is a common consequence in utero of turners?

Answer 42

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 \*\*\*similar thing happens with klinefelters syndrome **15% of spontaneous abortions ahve XO karyotype**

Question 43

What are the Sx's/signs of turner syndrome?

Answer 43

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

Question 44

Describe the hormonal effects of Turners syndrome and its effects on sex organ development

Answer 44

Question 45

What is Klinefelters syndrome? What is it a genetic abnormality of? how many males with these genetic abnormality actually express evidence of disease?

Answer 45

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

Question 46

Describe the hormonal effects of Klinefelters syndrome and how it affects sex organ development

Answer 46

Question 47

Are there only 2 sexes? What is the best way to determine if an individual is male or female?

Answer 47

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!