puberty and sex differentiation

Question 1

what are primordial germ cells?

Answer 1

• indifferent between male/female until week 7
• diploid cell precursors -> arise during gastrulation at week 3 and are epiblast derived
• precursors to sperm/egg

Question 2

what happens during weeks 3-7 ?

Answer 2

• cells proliferate via mitosis and migrate by amoebid movement to region of dorsal wall that will form the gonadal ridges –> guided via chemotaxis

Question 3

what is important about week 7?

Answer 3

determines male or female development

• differences are present now

female (XX) / male (XY)

Question 4

what is the importance of SRY?

Answer 4

• sex determining region y gene (on Y c)
• this is a conserved region across as mammals that encodes a controller gene testis determining factor gene
• this codes for a transcription factor (controller gene)

Question 5

at what week Does does development of the testes begin?

Answer 5

week 7

1) columns of cells from coelomic epithelium proliferate and penetrate deeply ->sex cords-> express of SRY –> Sertoli cells
2) sex cords surround the PGCs–> forming seminiferous tubules
3) migratory cells from mesenophric primordial form vasculature and leydig cells

Question 6

what do the sex cords form?

Answer 6

• Sertoli cells

Question 7

what is found within the seminiferous tubules?

Answer 7

• prospermatogonia (the PGCs)

Question 8

when does SRY expression stop?

Answer 8

once the sertoli and leydig cells form

• testes produce hormones leading to development of male reproductive system

Question 9

what differs with ovary development?

Answer 9

• same 3 cells arrive but in the absence of SRY expression (behave differently)–> default

Question 10

what is the default pathway?

Answer 10

• occurs from week 7 onwards
• absence of the Y chromosome (SRY(
• female gonad develops

Question 11

briefly outline the order of ovarian development

Answer 11

• sex cord cells do not penetrate deeply and cluster around PGCs (oogonia) forming primordial follicles
• mesospheric cells form vasculature and thecae cells
• no endocrine activity

Question 12

where is the wolffian duct and mullerian duct found?

Answer 12

WD–> male
MD–> female

gonads are bipotent, both structures exist at the indifference stage

Question 13

what occurs in the testis under the action of androgens and MIS?

Answer 13

androgens-> from leydig cells maintain wolffian ducts (epididymis) and the vas deferens

• MIS–> from immature Sertoli cells–> causes regression of the mullerian ducts

Question 14

what occurs in females under the absence of hormones?

Answer 14

• default pathway

- absence of AMH ducts develop

Question 15

what occurs during the development of the male external genitalia?

Answer 15

• androgen converted to DH
  T promotes male testes development
• catalysed by 5a-RD
• the genital tubercle develops into the penis
• uro-genital fold develops into spongy urethra
• labio-scrotal swelling develops into scrotal sac

Question 16

the female genitalia?

Answer 16

default pathway and no androgen is produced

• if they are not produced then we get female external genital development

genital tubercle-> clitoris
labio-scrotal swelling–> labia majora
uro-genital fold–> labia minora

Question 17

when does the definitive signs of puberty begin for males and for females?

Answer 17

males-> 13.4 yrs (ejaculation)

females -> 12.9 yrs (menstrual bleed)

Question 18

what hormone does the hypothalamus secrete ? and what does It do?

Answer 18

• GnRH
• produced in the arcuate nucleus (travels down the primary portal plexus)
• binds to GnRH R on gonadotrophs of APG
• stimulates release of gonadotrophins from the APG
• triggers gonadal activation via pulsatile GnRH secretion
• prolonged secretion leads to downregulation ofGnRH R on gonadotroph meaning less FSH/ LH release–> testes

Question 19

what is responsible for this pulsatile release?

Answer 19

• Kisspeptin 1
• 54 aa NT
• `acts on KIss1R/ GPR54
• KISS1 expression rises at puberty

Question 20

where does LH act ?

Answer 20

• produced by gonadotrophs

- acts on leydig, theca and granulosa cells

Question 21

where does FSH act?

Answer 21

• produced by gonadotrophs

- acts on sertoli and granulosa cells

Question 22

where does hCG act?

Answer 22

• produced by trophoblast cells

- acts on luteal cells (corpus luteum)

Question 23

what is the same between both sexes and what differs?

Answer 23

• HP axis secretion is the same (FSH, LH)
• its the gonadal secretions that differ between sexes

male-> testis-> inhibit, T

female -> ovary-> oestrogen and progesterone

Question 24

what determines the potency of sex steroids ?

Answer 24

• depends on how well they fit at the binding site of R
• some bind but don’t activate R (antagonists such as RU486) -> anti-P drug
• contraceptive pill-> P binds to other receptors too of same specificity s/e of acne

Question 25

sex steroids can be grouped into 3 families of?

Answer 25

• derived from cholesterol
• progestogens–> pregnancy (placenta)
• androgens->maleness (adrenals)
• oestrogens -> femaleness ( liver, adrenals, adipose, placenta)
• all bind to intracellular nuclear steroid response elements

Question 26

what do ovarian oestrogens do?

Answer 26

• induce growth of breasts and genitalia + axillary hair growth

Question 27

testicular androgens ?

Answer 27

• growth go pubic, facial and axillary hair, genitalia, enlargement of larynx and laryngeal muscles–> lengthening and thickening of vocal cords

Question 28

compare the difference of growth spurts between male and female

Answer 28

• girls grow 25cm
• girls grow 28cm
• boys begin 2 years later –> height take off is 10cm greater-> hence why males grow taller than females
• 24-36 average spurt length

Question 29

what causes fusion of the epiphyseal growth plates?

Answer 29

• higher levels of oestrogen inhibiting GH-IGF-1 axis (late puberty)
• cartilage is replaced with bone
• during early puberty there are low levels of oestrogen –> more GH stimulates liver and chondrocytes too