2- HPG axis and Puberty

Question 1

what is kisspeptin?

Answer 1

a small peptide neurotransmitter made in three different forms - all forms have 10 functional amino acids that partake in any activity

Question 2

in what hypothalamic nuclei are kisspeptin neurons expressed in? where do they project to?

Answer 2

arcuate nucleus

anteroventral periventricular nucleus

project to GnRH neurons in the hypothalamus with the kisspeptin receptor

Question 3

function of kisspeptin

Answer 3

unsure - presumed to be one of the triggers in puberty. inactivating mutations of the kisspeptin GCPR receptor cause failure to undergo puberty.

triggers GnRH release form hypothalamic GnRH neurons it projects to

Question 4

what is the structure of GnRH?

Answer 4

active peptide is 10aas long, secreted with an associated peptide 56aas long

Question 5

explain the importance of pulsatile GnRH secretion

Answer 5

constant GnRH secretion causes a block on FSH/LH secretion

slow frequent pulses of GnRH secretion = LH
fast frequent pulses of GnRH secretion = FSH

pulsatile secretion is needed as when GnRH binds to its GCPR receptor, it gets internalised as a G-protein second messenger, causes FSH/LH release, and is then put on the surface again

Question 6

describe the structure of the gonadotrophins

Answer 6

FSH, LH (and hCG) all have the same alpha subunit, different beta subunits

heterodimeric peptides - common alpha subunit, different beta subunits which are intertwined together

alpha subunit synthesised in excess - important for receptor binding

beta subunit confers specificity

Question 7

functions of FSH and LH in puberty?

Answer 7

FSH = stimulates growth of testis in males, folliculogenesis with steroid synthesis in females

LH = stimulates gonadal synthesis and secondary sexual characteristics

Question 8

what is puberty?

Answer 8

individuals going from a non-reproductive to reproductive state through physiological, psychological changes and the development of secondary sexual characteristics

Question 9

examples of secondary sexual characteristics in men and women

Answer 9

males = facial, pubic and axillary hair, growth of penis and scrotum

females = breasts enlarge (thelarche), pubic and axillary hair, periods (menarche)

Question 10

describe the three theories on what stimulates the onset of puberty

Answer 10

genetic reasons
- environmental or genetic factors affect maturation of GnRH synthesising neurons

body fat and nutrition
- malnutrition delays puberty, need 17-18% body fat to initiate puberty, 22% for menstruation

kisspeptin
- inactivating mutation in kisspeptin receptors = fail to undergo puberty

Question 11

define the two key endocrine events of puberty

Answer 11

adrenarche - maturation of cells in the adrenal gland for the release of androgens = leads to pubarche

gonadarche - follows adrenarche where the HPG axis is activated. FSH and LH synthesised and secreted

Question 12

describe the process of adrenarche

Answer 12

the first stage of puberty with an unknown trigger - involves the maturation/ growth and remodelling of adrenal glands to secrete androgens

triggers pubarche

cholesterol is taken in by the adrenal glands - converted to DHEA

DHEA is sulphated to DHEAS - adds a negative charge and makes it soluble in blood

DHEAS carried through circulation to target tissues - becomes testosterone or DHT and affects androgen receptors to trigger pubarche and other changes

Question 13

describe the process of gonadarche

Answer 13

‘mini puberty’ occurs between gestation and 2yrs post-natal with small GnRH pulsatile secretions before stopping

in puberty, occurs after adrenarche - HPG axis is activated, pulsatile GnRH release triggered by kisspeptin, FSH and LH secreted and binds to gonads

production of oestrogen progesterone and androgens in varying amounts in males and females

Question 14

describe GnRH pulsatile secretion during the different stages before and after puberty

Answer 14

before puberty - low levels, barely present

early-mid puberty - higher pulsatile levels at night, lower during the day

mid-late puberty - highest levels during the night, still high but lower during the day

adulthood - consistent pulsatile secretion during the day and night

GnRH pulsatile secretion highest at night towards late puberty

Question 15

describe epiphyseal puberty as a part of puberty

Answer 15

epiphyses are the rounded ends of bones that initially form separately to long bones = fuse to the main shaft of bone as person grows and ages

epiphyses are open when we’re young

during puberty when oestrogen isn’t present as HPG axis activates = linear growth is promoted. once oestrogen gets to a certain level the epiphyses fuse, linear growth stops

girls start growing earlier and stop sooner - get oestrogen earlier than boys

different epiphyses fuse at different ages

Question 16

what causes acne?

Answer 16

overproduction of sebum from sebaceous glands of pilosebaceous units

causes infection underneath = acne

Question 17

what is the purpose of sebum?

Answer 17

lubricant for hair
antibacterial
associated with different smell a person gives off during puberty

Question 18

what are the three pilosebaceous units? how are they influenced?

Answer 18

sebaceous PSUs

vellous PSUs - terminal (facial hair) and apocrine (pubic and axillary hair)

influenced by androgens - they all have sebaceous glands which produce sebum

Question 19

why is the consonance of puberty important?

Answer 19

puberty can happen at different ages but always in the same order - if it’s in the wrong order, indicates something is wrong

tanner scale of pubertal development used to tell what stage of development someone is at

Question 20

what are the major stages of puberty?

Answer 20

adrenarche and gonadarche - activation of HPG, release of gonadotrophins and androgens, adrenal gland maturation

developing secondary sexual characteristics - breast development and pubic hair in females, testes enlarge and voice deepening in men

growth spurt - low oestrogen levels once HPG axis is activated promoted linear growth. earlier onset and ending for females. release of growth hormones encourages growth.

changes in body composition, reproductive organs mature - menarche and spermarche = influenced by oestrogen and testosterone

psychological changes - development of a sexual identity, interest in relationships

Question 21

what is precocious puberty?

Answer 21

early puberty - before 10yrs in females, before 11/12 years in males

Question 22

what are the two types of precocious puberty?

Answer 22

central gonadotrophin dependent puberty = has consonance

pseudo gonadotrophin independent puberty = has no consonance

Question 23

what are the potential causes of central precocious puberty? what are the results of it?

Answer 23

excess GnRH secretion

excess gonadotrophin secretion - can be from a pituitary tumour or early HPG axis activation

hormones secreted act on the gonads - leads to early development of sex development and secondary sexual characteristics

accelerated linear growth, advanced bone ages, increased FSH, LH, oestrogen and testosterone

Question 24

what is the treatment for central precocious puberty?

Answer 24

GnRH analogues/ antagonists = suppress puberty until an appropriate age

surgery or chemotherapy if caused by a tumour

evaluated on a case-by-case basis with psychological assistance

Question 25

what is pseudo-precocious puberty?

Answer 25

gonadotrophin independent early puberty where consonance isn’t maintained

Question 26

what are the potential causes of pseudo-precocious puberty?

Answer 26

testotoxicosis - activating mutation of LH receptor leading to early androgen production by Leydig/ theca cells. the LH receptor thinks it’s bound by LH when it isn’t

sex steroid secreting tumour - exogenous steroids produced

McCune Albright - activation of adenylyl cyclase, hyperactivity of signalling pathways leading to gonadotrophin hormone production

congenital adrenal hyperplasia - androgens produced by adrenal glands too early, typically once foetus is born

Question 27

why isn’t consonance maintained with pseudo-precocious puberty?

Answer 27

oestrogen and testosterone produced but typically LH, FSH, GnRH or adrenarche are suppressed

in males = no spermatogenesis
in females = no folliculogenesis

Question 28

what are potential causes for pubertal delay?

Answer 28

constitutional delay where puberty doesn’t start
- can be caused by many factors such as malnutrition, chronic illness, genetics

hypogonadotrophic hypogonadism - low FSH and LH means low gonad activity as they aren’t stimulated

hypergonadotrophic hypogonadism - high FSH and LH but gonads aren’t working, prevents development of secondary sexual characteristics

Question 29

what are potential causes for hypogonadism?

Answer 29

gonadal dysgenesis - low sex steroid production from gonads

congenital syndromes - e.g. Turner syndrome leading to streak ovaries, Klinefelter’s syndrome