Lecture 12 (Luckman)

Question 1

adolescence v puberty

Answer 1

“Adolescence is the phase of gradual transition between childhood and adulthood”
involves brain development and physical changes.
risky behaviour

puberty - physical sexual changes to become fertile.
Secondary sex characteristics appear, physical growth, reproductive competence is achieved.

Question 2

brain development during adolescence

Answer 2

subcortical regions - amygdala + NAc develop much faster than frontal areas (PFC)

imbalance can lead to risky or emotional behaviour

Question 3

role of the amygdala?

Answer 3

emotional processing

Question 4

adolescent responses to external stimuli

wrt. facial expressions and money

Answer 4

facial expressions show increased amygdala response in adolescence > and increased NAc response for monetary reward

Question 5

HPG axis? (general)

GnRH (x2)

FSH, LH (+Oe)

Inhibin (+follistatin)

Neurosteroid axis

Answer 5

Hypothalamic-Pituitary-Gonadal (HPG) Axis

GnRH causes LH/FSH release.
LH/FSH activated production of sex steroids, feedback onto hypothalamus/anterior pituitary gland loop.

GnRH(Hyp) –(hypophyseal portal)–> binds GnHRs on secretory cells of adenohypophysis–>LH, FSH (blood stream)

FSH,LH (F)- activate ovaries to produce oestrogen and inhibin, oestrogen forms -ve fb loop (inhibiting GnRH production in Hyp)

Inhibin (+follistatin) inhibits activin (peripherally produced GnRH stimulator)

Recent research has shown that a neurosteroid axis exists, which helps the cortex to regulate the hypothalamus’s production of GnRH

Question 6

when does onset of puberty occur in females?

Answer 6

when sufficient nutrients attained.

obesity advances onset.

undernutrition delays onset.

physical excercise delays. onset.

Question 7

Menstruation

Oestrogen, FSH, LH, Progesterone

Answer 7

FSH stimulates egg maturation and oestrogen release

oestrogen peaks day 14 just before ovulation, stops FSH production as only 1 egg needed and stimulates LH release.

Day 14 peak LH ovulation day, LH causes mature egg release to uterus which can now be fertilised.

Uterus lining thickens, maintained by Progesterone.

progesterone decreases when no pregnancy occurs, lining sheds and menstruation day 28.

Question 8

HPG axis in pregnant/non pregnant

Answer 8

oestrogen feeds back onto hypothalamus/anterior pit and progesterone inhibits hypo/anterior pit.

+ve fb loop between oestrogen and LH prepares follicle (in ovaries) and uterus for ovulation and implantation

empty follicle sac releases progesterone following egg release to inhibit Hyp and aPit (stops fb loop)

if conception occurs, placenta secretes progesterone and mother cannot ovulate again, if not, decreasing progesterone will allow Hyp to restart GnRH secretion

Question 9

as males age

T

Answer 9

less testosterone.

decrease muscle mass
increase fat
lose libido
impotence
decreased attention

Question 10

kisspeptin

Answer 10

Kiss1 gene.

binds GPCR54

GPCR54 (renamed Kiss1R)

essential for pubertal development and reproductive function

Question 11

GPCR54 mutations

Answer 11

GPR54 mutations/deletions lead to sexual immaturity, failure of gonadal function and hypogonadotropism

infertile and less sexual hormones

Question 12

kisspeptin structure

Answer 12

In primates, the Kiss1 gene encodes a 54 amino acid peptide (kp-54)
In rodents, the mature kisspeptin product is 52 amino acids.

precursor prepro kisspeptin 125 AA long.

numerous kisspeptins of various length.

Question 13

where is kisspeptin found?

Answer 13

Brain: - AVPV/PeN (anteroventral periventricular nucleus-periventricular nucleus continuum)
- ARC (arcuate nucleus)

Peripheral tissues: placenta, ovary, testis, pituitary, pancreas and adipose tissue

Question 14

where is the Kiss1R gene found?

Answer 14

Brain: hypothalamus, preoptic area, hippocampus, habenula, amygdala

Peripheral tissues: placenta, testis, pituitary, pancreas and kidney

Question 15

kisspeptin distribution in the brain across species?

Answer 15

varies- table

Question 16

GnRH and kisspeptin?

Answer 16

GnRH-Ns don’t have oestogen receptors, so how does HPG work?

kisspeptin have oestrogen receptors and androgen receptors.

GnRH have kisspeptin receptors.

Question 17

AVPN and ARC GnRH neurons differences in rat?

Answer 17

AVPV - positive feedback in adult females
ARC - negative feedback in adults of both sexes.

AVPV project to cell bodies of GnRH neurons.
ARC project to axon terminals of GnRH neurons.

sexual dimorphism in Kiss1cells in AVPV.
25x more kisspeptin expression in females than males.
need to detect the big changes in oestrogen just before ovulation to produce LH surge on day of ovulation.

AVPV - also prod galanine and tyrosine hydroxylase.
ARC - also produce neurokinin B, dynorphin (Kndy neurons)

Question 18

HPG axis in males

GnRH, LH, T, FSH and inhibin

Answer 18

In males, GnRH, LH, FSH production similar but effect different

LH stimulates the interstitial cells (testes) to produce testosterone (normal spermatogenesis, inhibits HYP)

FSH plays a role in spermatogenesis. Only small amounts of estrogen are secreted in males. FSH stimulates sustentacular cells to release ABP (promotes T binding).

Inhibin is produced by the spermatogenic cells, which, also through inhibiting activin, inhibits the hypothalamus. After puberty these hormones levels remain relatively constant.

Question 19

Leptin, insulin and ghrelin on the HPG axis (+Kisspeptin)

Answer 19

Leptin and insulin have stimulatory effects and ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin also influences GnRH secretion.

Question 20

HPG axis and puberty

Answer 20

The activation of the HPG axis in both males and females during puberty also causes individuals to acquire secondary sex characteristics.