Hypothalamic-pituitary-gonadal axis II

Question 1

What is puberty?

Answer 1

the period of sexual maturation, during which a person becomes capable of reproducing

Question 2

What is puberty defined as clinically?

Answer 2

increased breast development in females (thelarche)

increased testicular volume in male

Question 3

What are the endocrine events of puberty?

Answer 3

Adrenarche

Gonadarche

Question 4

What is Adrenarche (6/8-15 years)?

Answer 4

maturation of adrenal glands

• foetal zone shrinks and definitive zone grows once foetus is born
• definitive zone releases adrenal androgens DHEA&DHEAS that cause maturation of adrenal glands (6/8-15 years old)

Question 5

Where are DHEA and DHEAS synthesized?

Answer 5

in zona reticularis of adrenal cortex

Question 6

What is the consequence of adrenarche?

Answer 6

Pubarche

• growth of pubic and axillary hair
• growth in height
• increased sebum production causing acne
• infection and abnormal skin keratinisation, causing acne

Question 7

What is Precocious Puberty?

Answer 7

a condition in which puberty begins before the age of 8 in girls and 9 in boys

Question 8

What is Gonadarche (11 years)?

Answer 8

reactivation of HPG axis and GnRH secretion

• at 16th gestational week, HPG axis is activated for sexual differentiation
• HPG axis deactivated after birth
• HPG axis reactivated during puberty (11 years)

Question 9

When are the pregnancy scans?

Answer 9

12-13 weeks

20 weeks

Question 10

At what pregnancy scan can the baby’s sex be revealed and why?

Answer 10

not at the 12-13 week scan, but at the 20th week scan

this is because activation of HPG axis which results in sexual differentiation is at 16th gestational week

Question 11

How can we study changes in pattern of GnRH secretion?

Answer 11

by observing changes in pattern of LH secretion because it mimics GnRH secretion and easier to obtain
-(GnRH secreted into hypophyseal portal vein)

Question 12

What is the Effect of body fat on GnRH?

Answer 12

Individuals with anorexia nervosa or who undergo intensive training:

• reduced response to GnRH
• decreased gonadotrophin levels
• amenorrhoea in females (absence of menstrual periods)

Restored when nourished/exercise stopped

Question 13

Describe the Stimulation of onset of puberty.

Answer 13

kisspeptin
environmental/genetic factors
body fat/nutrition
maturation of GnRH neurones

Question 14

How can leptin and ghrelin mediate puberty regulation?

Answer 14

they feed into hypothalamus and regulate kisspeptin, which in turn regulates onset of puberty

Question 15

Describe the Inactivating mutations of KISS1 receptor or Kisspeptin gene.

Answer 15

Hypogonadotrophic Hypogonadism (HH)
-failure to enter puberty

Question 16

What is the Activating mutations of KISS1 receptor?

Answer 16

Precocious puberty

Question 17

What is consonance?

Answer 17

smooth ordered progression of changes that occur during puberty

• ORDER of pubertal changes is same in everyone
• AGE OF ONSET/PACE/DURATION of changes will vary

Question 18

Describe the Tanner stages of puberty.

Answer 18

5 stages of physical measures of development used to clinically diagnose pubertal disorders in/out of consonance based on:

1) Pubic and Axillary Hair Growth
2) Testicular Volume and Penile Length in males
3) Breast Development in females

Question 19

What is a growth spurt?

Answer 19

Biphasic effect of oestrogen on epiphyseal growth:
>first starts with low oestrogen levels- linear growth and bone maturation
>followed by high oestrogen levels- epiphyseal bone fusion

Question 20

What is a pilosebaceous unit?

Answer 20

structure consisting of:

>hair+hair follicle+arrector pili muscle+sebaceous gland

Question 21

What are the Main types of pilosebaceous units?

Answer 21

Sebaceous PSU

Vellus PSU

Question 22

What are the Effect of Androgens on PSUs?

Answer 22

Sebaceous PSU
-androgens increase sebum production, resulting in acne

Vellus PSU
-androgens differentiate vellus PSUs into:
>terminal PSUs responsible for beard growth
>APO-PSU responsible for axillary and pubic hair

Question 23

What are the Psychological changes in puberty?

Answer 23

• increasing need for independence
• increasing sexual awareness/interest
• development of sexual personality

*later maturation is associated with better adjustment because psychological and sexual behaviours are occuring in sync

Question 24

What is Precocious Puberty?

Answer 24

a condition in which puberty begins before the age of 8 in girls and 9 in boys

Question 25

What is a common cause of precocious puberty?

Answer 25

premature activation of HPG axis

Question 26

What is the cause of Gonadotrophin Dependent Precocious Puberty?

Answer 26

Could be due to:

• excess GnRH secretion
• pituitary tumour causing excess gonadotrophin secretion

Question 27

What is the cause of Gonadotrophin Independent Precocious Puberty?

Answer 27

Could be due to:
-testoxicosis (activating mutation of LH receptor in testis)

• sex steroid secreting tumour causing early gonadal maturation
• exogenous steroids causing early gonadal maturation
• McCune Albright Syndrome: activating mutation in GNAS1 gene encoding Gas subunit, causing hyperactivity and overproduction of hormone

Question 28

What is Pubertal Delay?

Answer 28

absence of secondary sexual characteristics by 13 years old in girls (or absence of menarche by 18) or 14 years old in boys

Question 29

What is a common cause of pubertal delay?

Answer 29

delayed HPG axis activation

Question 30

What is Constitutional Pubertal Delay?

Answer 30

affects growth and puberty

secondary to chronic illnesses e.g. diabetes, cystic fibrosis

Question 31

What is Hypogonadotropic hypogonadism?

Answer 31

FSH+LH are low due to:
-Kallman’s syndrome: X-linked KAL1 gene mutation, impaired GnRH neurone migration to hypothalamus during development

• Inactivating mutation of KISS1 receptor or kisspeptin gene
• other mutations causing defects in GnRH production

Question 32

What is Hypergonadotropic hypogonadism?

Answer 32

FSH+ LH are elevated due to:
-gonadal dysgenesis and low sex steroid levels (no negative feedback)

-gonadal dysgenesis in those with normal karyotype caused by viral mutations e.g. mumps

-gonadal dysgenesis resulting from abnormal karyotype:
>Klinefelter’s syndrome (XXY) in males; characterised by feminine features such as breast development
>Turner’s syndrome (XO) in females; characterised by “streak ovaries” and being shorter than normal