Reproduction L02 Neuroendocrinology Of Puberty

Front 1

What are the first signs of puberty for males and females?

Back 1

males testis, girls breast buds

Front 2

1. For both males and females, graphically demonstrate the temporal relationship between the different aspects of puberty development (hint, thing ranges and relative relationships)

2. Give average ages for these milestones

Back 2

Male pubertal growth
• 11.5 testicular development
• 12.9 adrenarche
• 13.4 penile enlargement
• 14 PHV(growth spurt)

Female pubertal growth
• 9.8 years thelarche
• 10.5 adrenarche
• 12 PHV (growth spurt)
• 12.8 menarche

Front 3

Where is earlier menarche not seen?

Back 3

poor rural areas and higher altitudes

Front 4

What is the average age of breast budding? What is the range of age for breast budding? What is the duration of breast development?

Back 4

avagerage age of breast dev: 10.5 yrs… Age range for budding= 8 yr, 6 mo - 13 yrs… Duration= 4 yrs

Front 5

1. What is the average age (range) of onset of pubertal development in males and females?

2. What are the first signs of puberty for boys and gilrs?

3. When will pubic hair begin?

4. At what age is the PHV in boys and girls

Back 5

1. What is the average age (range) of onset of pubertal development in males and females? Males: >9-<14… Females: >8 <13

2. What are the first signs of puberty for boys and gilrs? Girls=breast budding... Boys= testicular enlargement/scrotal thinning

3. When will pubic hair begin? Six months after start of puberty

*Note: For BOTH Boys and Girls, pubic hair may be the heralding sign of puberty, where breast budding or testicular enlargement will begin 6 months later.

4. PHV:
a) Girls=12 (9 cm/yr)
b) Boys=14 yrs

Front 6

What is the mean duration of pubert?

Back 6

4.2 yrs = mean duration of puberty

Front 7

what is the mean age of menarche?

Back 7

what is the mean age of menarche? 12.8 y (12.5 - 12.75 m)

Front 8

T/F breat and pubic hair do not show discordance.

Back 8

false, normal girls may be B4 and P1 for example... in other words they don't progress evenly

Front 9

What is the age (range) of onset of puberty age in boys… what is the mean age on onset of puberty in boys?

Back 9

Range of onset 9-14 yrs… mean age of onset of puberty = 11.5 yrs

Front 10

1. What stimulates leydig cells? and what percentage of testicular volume do the leydig cells account for?

2. What stimulates Sertoli cells? and what percentage of testicular volume do the sertoli cells (in tubules) account for?

Back 10

1. LH stimulation of Ledig cells (10% volume)

2. FSH/T stimulation of tubules (90% volume)

Front 11

For boys, in terms of Genital Development (G2-G5) what is PHV most closely related to? Give an example.

Back 11

PHV in boys is associated with gonadal development… between G4-G5 --> @ 14y with ~10.3 cm/yr

Front 12

In pubic hair dev in boys, what is the Tanner range and what is the duration in years? When does axillary hair develop. When does adult distribution of hair occur?

Back 12

In pubic hair dev in boys, what is the Tanner range and what is the duration in years? P2-P5, 4yrs… When does axillary hair develop? 1-2 yrs after pubic hair development onset… When does adult distribution of hair occur? Usually no sooner than 20 y/o

Front 13

What 4 things explain the difference in male and female height?

Back 13

1) > prespurt growth in boys… 2)Boys are abouty 10 cm taller than girls when they begin their growth spurt… 3) > puberty gain during growth spurts in males… 4) > postspurt growth in GIRLS… SHORT ANSWER: BOYS START PUBERTY LATER… and GREATER OVERALL GROWTH DURING PUBERTY

Front 14

During puberty there is an increase of GH by 2-3 times compared to prepuberty. (1) what is believed to cause this increase… (2) What is primarily responsible for growth spurts?

Back 14

During puberty there is an increase of GH by 2-3 times compared to prepuberty. (1) what is believed to cause this increase? T and E. (2) What is primarily responsible for growth spurts? GH and Gonadal Steroids

Front 15

With respect to menarche, when do girls do most of their growth?

Back 15

Girls do most of their growth before menarche

Front 16

What hormone do girls have more of at the start of puberty, which may explain why girls grow more at the start of puberty as compared to boys?

Back 16

Girls have higher levels of GH at the beginning of puberty as compared to boys.

Front 17

When do girls have PHV?

Back 17

1.3 years before menarche at B3

Front 18

When do boys have their PHV?

Back 18

Boys increase in height velocity by G3 with a peak between G4-5… in other words after testicular development

Front 19

What effect do PURE androgens have on GH?

Back 19

Pure androgens have less of a stimulating effect that T or E and may even inhibit GH.

Front 20

What is required for epiphyseal plate closure in both girls and boys?

Back 20

Estrogen is required for epiphyseal plate closure

Front 21

Which 5 hormones are required for growth for both boys and girls? (hint: not just gonadal hormones)

Back 21

T, E, GH, IGF-1 and thyroid hormone are required for growth

Front 22

What meant by the biphasic effects of Estrogen in terms of growth?

Back 22

Low doses --> growth… high dose --> epiphyseal plate closure

Front 23

what may explain growth spurts in androgen insensitive males?

Back 23

T -(aromatization)--> E

Front 24

Where do the GnRH neurons originate from? Where do they go? What do they become?

Back 24

The GnRH neurons originate from the Olfactory placode (which will eventually become the nasal septum and cribiform plate) --> to the basal hypothalamus and arcuate region… where they become LHRH pulse generator

Front 25

What guides the LHRH cells to the site of the LHRH pulse generator?

Back 25

NCAM guides the LHRH cells

Front 26

What causes Kallman's syndrome?

Back 26

What causes Kallman's syndrome? Failure of LHRH cells to migrate (defect in gene at Xp22.3)

Front 27

T/F Kallman's syndrome is autosomal recessive?

Back 27

False, Kallman's syndrome is X-linked; related to a migration protein

Front 28

In which week is LHRH migration complete? 2, 3, 4, 5, 6?

Back 28

4.5 weeks

Front 29

What is required for the hypothalamic-pituitary-gonadal unit to function?

Back 29

What is required for the hypothalamic-pituitary-gonadal unit to function? Blood flow

Front 30

T/F pulsative LHRH are detectable in the fetus, but in the absence of negative feedback.

Back 30

True: LHRH is seen in the fetus with corresponding rises in FSH and LH… false: there is negative feedback of the GnRH pulse by 120 days and carries on thru late pregnancy

Front 31

T/F fetal LH is higher in females than in males, which corresponds to low testosterone production in male fetuses.

Back 31

True: LH is higher in the female fetus… but by week 7-16 male fetus testosterone is producing its highest levels of the pregnancy

Front 32

In which infant, male or female, do you see a marked increase in LH within minutes of birth? What consequence does this have?

Back 32

Male infants have an increase in LH within minutes of birth --> leading to a 10x increase in testosterone within hours of birth.

Front 33

Both male and female infants undergo a 'mini-puberty", what is the time line and how long does it last?

Back 33

Females: have an increase in estrogen at the second week --> lasting for 1-2 years… Males: lasts for 6 months

Front 34

In which infant does estrogen enter the brain, what is the effect of this?

Back 34

In Males: T -(aromatization)--> E --> crosses BBB --> masculinization of brain.

Front 35

What two mechanism are believed to account for the suppression of the LHRH generator in the prepubertal child?

Back 35

LHRH generator suppression in childhood: (1) highly sensitive steroid hormone DEPENDENT negative feedback (since there are very low levels of FSH/LH)… (2) Steroid INDEPENDENT intrinsic CNS inhibition of the LHRH pulse generator

Front 36

What do gonadal dysgenesis in Turners children (or suppressed adrenal steroids) in the absence of low levels of FSH/LH suggest about the control of the LHRH pulse generator?

Back 36

What do gonadal dysgenesis in Turners children (or suppressed adrenal steroids) in the absence of low levels of FSH/LH suggests that the LHRH pulse generator is under the intrinsic control of CNS

Front 37

What does precocious puberty seen in children with hypothalamic neoplasms (and Hypothalamic Hamartomas) support?

Back 37

Intrinsic control of the CNS over the pulse generator: (1) in hypothalamic neoplasms the neural pathways are blocked thus leading to activation of the the LHRH pulse generator… (2) hypothalamic Hamartomas are ectopic LHRH pulse generators, which are not inhibited by the CNS --> precocious puberty.

Front 38

What is the significance of 48 kg for young women?

Back 38

48 kg is the invariant mean weight needed to initiate puberty in young women

Front 39

When is CNS control of the LHRH pulse generator first decreased in the onset of puberty? What effect does this have on Neg Feedback?

Back 39

(1) CNS suppression of the LHRH pulse generator is decreased in NON-REM sleep during the onset of puberty, (2) making the pulse generator less sensitive to gonadal steroid negative FB.

Front 40

What is the average LH peak (Peak/?min) pattern?

Back 40

LH peak every 120 minutes

Front 41

What is the rate of LH peaks (per hour) in mid follicular phase of adult women?

Back 41

1/LH peak every hour during mid-follicular phase

Front 42

what is the difference between FSH and LH between prepubertal boys and girls? What female pathology does this explain?

Back 42

(1) FSH is stored in greater quantity in girls. Girls are more sensitive to LHRH release of FSH. LH is the same in boys and girls… (2) this explains why precocious puberty is seen more often in girls than in boys

Front 43

Why are 55-90% of cycles anovulatory in first two years after menarche?

Back 43

immature LHRH pulse generator in resonse to high levels of estrogen. Mature LHRH pulse generator is inhibited by low levels of estrogen, but stimulated by high levels of estrogen --> LH surge --> ovulation

Front 44

Which occurs first, adrenarche or gonadarche?

Back 44

adrenarche occurs before gonadarche

Front 45

Name 3 enzymes of the ZR precipitate onset of adrenarche? What do they produce?

Back 45

enzymes such as 17, 20 desmolase, 17 hydroxylase, 3ß hydrodrosteroid dehyrogenase in the ZR --> DHEAS and DHEA --> adrenarche

Front 46

Pubic hair development at what age determines premature adrenarche?

Back 46

Males: B/4 age of 9 yrs. Females: B/4 age of 8 yrs = premature adrenarche

Front 47

Is sexual development seen in premature adrenarche?

Back 47

Is sexual development seen in premature adrenarche? NO

Front 48

In which sex is premature adrenarche seen more often?

Back 48

In which sex is premature adrenarche seen more often? Females

Front 49

Which enzymes are implicated in classic and nonclassic forms of CAH cause premature adrenarche?

Back 49

21, 11ß and 3ß are implicated in the premature adrenarche related to CAH

Front 50

What can carbohydrate intolerance lead to?

Back 50

Carbohydrate intolerance lead to premature adrenarch

Front 51

What effect does premature adrenarche have on the following? Bone age (before adulthood), average height (before adulthood), average final height.

Back 51

What effect does premature adrenarche have on the following? Bone age (before adulthood) ADVANCED , average height (before adulthood) ABOVE AVERAGE, average final height NORMAL

Front 52

What effect does premature adrenarche have on ovarian androgen?

Back 52

premature adrenarche may lead to OVARIAN HYPERANDROGENISM.

Front 53

When should an ACTH be given to children suspected of premature adrenarche?

Back 53

When should an ACTH be given to children suspected of premature adrenarche? Increased bone age, virilization, cystic acne, cliteral hypertrophy, or have an elevated 17 hydroxyprogesterone and DHEA levels

Front 54

T/F premature thelarche is followed by an abnormal puberty.

Back 54

T/F premature thelarche is followed by an abnormal puberty. FALSE

Front 55

Is premature thelarch bilateral or unilateral? When is premature thelarche usually seen (what age)?

Back 55

Bilateral… usually seen at 2, not normally seen after 4 years old.

Front 56

Which product is implicated in premature thelarche?

Back 56

estrogen containing hair creams is implicated in premature thelarche

Front 57

What happens to the FSH/LH ratio in premature thelarche? What happens to estrodiol levels? Prolactin?

Back 57

What happens to the FSH/LH ratio in premature thelarche? it is reversed LH high, with FSH low… (2) What happens to estrodiol levels? Normal or elevated… (3) Prolactin NORMAL

Front 58

Where does "inhibin" have its effect and where is it released from?

Back 58

Gonads --> inhibin --> at level of pituitary

Front 59

T/F HPG axis is stimulated by stress, emotion, visual/olfactory stimuli.

Back 59

T/F HPG axis is stimulated by stress, emotion, visual/olfactory stimuli… TRUE

Front 60

At what age does GABA have a greater GnRH inhibitory effect?

Back 60

At what age does GABA have a greater GnRH inhibitory effect? PREPUBERTY

Front 61

Where are granules of GnRH stored?

Back 61

Where are granules of GnRH stored? GnRH secreting neurons w/in the arcuate nucleus of the Medial basal hypothalamus (MBH)

Front 62

What is the rate of GnRH pulsative secretions?

Back 62

What is the rate of GnRH pulsative secretions? 70-90 min intervals

Front 63

which is true of FSH and LH: both are amino acids, they share a common beta subunit.

Back 63

Both FALSE: FSH and LH are GLYCOPROTEINS, they share a common ∂ unit, but have a different ß subunit

Front 64

Which of the following are inhibitory to the GnRH pulse? Estrogen, androgens, progestogens, activin, inhibin, follistatin

Back 64

Which of the following are inhibitory to the GnRH pulse? Estrogen (has both neg & pos)… / androgens, progestogens, inhibin, follistatin --> INHIBITIORY… Activin --> STIMULATORY

Front 65

T/F GABA inhibits the onset of puberty

Back 65

TRUE

Front 66

T/F Skeletal maturation effects onset of puberty and the exact trigger of puberty is well known.

Back 66

TRUE: Skeletal maturation effects onset of puberty… FALSE: exact trigger of puberty is well known.

Front 67

Which is pulsative, LH or FSH? When?

Back 67

FSH is pulsative in early infancy in girls. LH is pulsative early infancy in males… LH is pulsative in both males and females in puberty

Front 68

Which of the following is true of changes HPG changes at puberty: (1) increased sensitivity to Neg FB --> decreased pulsative GnRH… (2) increased sensitivity of pituitary gonadotrophs --> decreased LH/FSH secretions… (3) increased responsiveness of gonads to LH/FSH --> increased gonaldal steroid production

Back 68

Which of the following is true: (1)FALSE: DECREASED sensitivity to Neg FB --> INCREASED pulsative GnRH… (2) FALSE: increased sensitivity of pituitary gonadotrophs --> INCREASED LH/FSH secretions… (3) TRUE: increased responsiveness of gonads to LH/FSH --> increased gonadal steroid production

Front 69

What effect does leptin have on the LHRH pulse generator? Why does this make sense?

Back 69

What effect does leptin have on the LHRH pulse generator? STIMULATES… Why does this make sense? Obesity hastens puberty

Front 70

What is gonadarche and what does it result from?

Back 70

Gonadarche is a rise in gonadal steroids that result from the HPG axis activation

Front 71

T/F adrenarche is dependent upon gonadal steroid production

Back 71

T/F adrenarche is dependent upon gonadal steroid production FALSE

Front 72

What 3 things influence secondary sexual development?

Back 72

What 3 things influence secondary sexual development? Gonadarche, adrenarche and physical changes caused by exposure to E and A

Front 73

T/F estrogen causes breast development only in girls

Back 73

T/F estrogen causes breast development in boys and girls. FALSE… BOTH BOYS AND GIRLS

Front 74

T/F Androgens cause body hair, body odor, and acne in both boys and girls.

Back 74

T/F Androgens cause body hair, body odor, and acne in both boys and girls. TRUE

Front 75

What is the average height gain for girls during puberty?

Back 75

What is the average height gain for girls during puberty? 9 inches

Front 76

How long after the onset of puberty does Menarche begin?

Back 76

How long after the onset of puberty does Menarche begin? 2-2-1/2 years

Front 77

What is the average height gains for boys during puberty?

Back 77

What is the average height gains for boys during puberty? 11 inches

Front 78

in the Tanner stages, what does 1 equate to?

Back 78

1= no puberty… (there is no zero)

Front 79

Does gynacomastia usually regress in young boys?

Back 79

Does gynacomastia usually regress in young boys? YES

Front 80

What is used to cause the regression of breast development in gynacomasty seen in young men?

Back 80

What is used to cause the regression of breast development in gynacomasty seen in young men? Surgery or an aromatase inhibitor

Front 81

T/F it can take up to 6-8 months for the first growth spurt to occur in young men after the onset of puberty.

Back 81

T/F it can take up to 6-8 months for the first growth spurt to occur in young men after the onset of puberty. TRUE

Front 82

Name two normal variants of normal puberty

Back 82

Name two normal variants of normal puberty: 1) constitutional delay… 2) familial early or rapid maturation

Front 83

Which results in normal final height 1) constitutional delay… 2) familial early or rapid maturation

Back 83

Which results in normal final height 1) constitutional delay… 2) familial early or rapid maturation… BOTH

Front 84

What is anosmia? What can it result from?

Back 84

What is anosmia? LACK OF SMELL... What can it result from? KALLMAN SYNDROME

Front 85

T/F Kallman syndrom results in eucoidism because there is no puberty and no fusing of growth plates.

Back 85

T/F Kallman syndrome results in eucoidism because there is no puberty and no fusing of growth plates. TRUE

Front 86

Which of the following is not true of HYPOTHALAMIC HAMARTOMA? Presents at 2-4 years old, heteropic mass of GNRh secreting neurons, acts as ectopic pulse generator, activation of HPG axis in central precocious puberty, does not resond to Rx.

Back 86

Which of the following is not true of HYPOTHALAMIC HAMARTOMA? TRUE: heteropic mass of GNRh secreting neurons, acts as ectopic pulse generator, activation of HPG axis in central precocious puberty… FALSE: Presents at 2-4 years old, does not resond to Rx.... PRESENT AT BIRTH... RESPONDS TO RX

Front 87

Which results in delayed puberty, hyperpituitarism or hypo?

Back 87

Which results in delayed puberty, hyperpituitarism or hypo? HYPOPITUITARISM

Front 88

What is a sign of hypopituitarism in male infants?

Back 88

What is a sign of hypopituitarism in male infants? Micro-penis as well as midline structural abnormalities

Front 89

What is the effect on final height in central precocious puberty?

Back 89

severe short stature

Front 90

What are included in the work up for CPP?

Back 90

GnRH stimulation test (to check for effects on LH and FSH… should be little increase) and MRI scan

Front 91

Name 2 syndromes of gonadal abnormal puberty.

Back 91

Name 2 causes of gonadal abnormal puberty: Turner syndrome (delayed puberty) and McCune-Albright syndrome (precocious puberty)

Front 92

T/F in Turner syndrome, ovaries start out normal but undergo atresia.

Back 92

T/F in Turner syndrome, ovaries start out normal but undergo atresia. TRUE

Front 93

Why do ovaries undergo atresia in Turner syndrome?

Back 93

Why do ovaries undergo atresia in Turner syndrome? Two x chromosomes are required to maintain normal ovaries

Front 94

What is the triad for McCune-Albright syndrome?

Back 94

What is the triad for McCune-Albright syndrome? Café au lait skin pigmentation (mosaic distribution), fibrous bone dysplasia and precocious puberty

Front 95

What is the etiology behind the McCune-Albright syndrome?

Back 95

What is the etiology behind the McCune-Albright syndrome? Activating mutation in Gs∂ --> hyperfx of endocrine tissue --> large ovarian cysts in girls