HPG axis 2

Question 1

kisspeptin

Answer 1

family of peptides
encoded by kiss-1 gene
54 aa (full form)
plasma kisspeptin levels are very low

Question 2

kisspeptin receptor

Answer 2

GPR54 (GPCR)
previously orphan receptor because ligand was unknown (kisspeptin)
located in testes and placenta

Question 3

kisspeptin levels during pregnancy

Answer 3

several thousand fold increase

Question 4

role of kisspeptin in cancer

Answer 4

metastasis (spread of primary tumours to other sites of the body)
tumour cell lines transfected with normal chromosome 6 - remained tumourgenic but lost ability to metastasise
kiss-1 gene on chromosome 6 is a suppressor of metastasis

Question 5

which disorder is kisspeptin and GPR54 linked to

Answer 5

hypogonadotrophic hypogonadism
impaired pubertal maturation and lack of reproductive function
different forms (mainly due to genetic defects)

Question 6

seminara et al., 2023 study

Answer 6

In saudi arabia, three marriages between 1st cousins - experienced infertility
detected mutations in GRP54 gene
GPR54 KO in mice - no puberty and reproductive organs remained undeveloped
lack of gonadal hormones and LH
GRP54 similar to kisspeptin KO

Question 7

intraperitoneal injection of kisspeptin

Answer 7

Increasing kisspeptin increases LH/FSH/test/oestro
adv: shows physiological response in whole animal, simple to conduct
dis: does not locate where kisspeptin is acting

Question 8

intracerebroventricular cannulation of kisspeptin (cannula in cerebral ventricles)

Answer 8

Increasing kisspeptin increases LH/FSH/test/oestro
adv: identifies direct effect of kisspeptin in CNS w/o peripheral effects
dis: does not identify where kisspeptin acts, difficult and expensive

Question 9

intranuclear cannulation of kisspeptin (into specific brain regions)

Answer 9

adv: identfies direct effect of kisspeptin on specific neuronal populations
dis: difficult and expensive

Question 10

effect of kisspeptin

Answer 10

direct release of GnRH and LH

Question 11

receptors which ARC and AVPV kisspeptin neurons express

Answer 11

oestrogen receptor-a
oestrogen receptor -B
androgen receptor

Question 12

AVPV and ARC kisspeptide neuron activity (Han et al., 2005)

Answer 12

AVPV neurons only active in puberty
ARC neurons active in childhood

Question 13

what does the kisspeptin neurons in the ARC express (KNDy neurons)

Answer 13

kisspeptin
neurokinin B (NKB) stimulatory
dynorphin (inhibitory)

Question 14

effect of estrogen on KNDy neurons

Answer 14

reduces kisspeptin, reduces NKB, increases dynorphin, decreased GnRH release and LH pulse

Question 15

what causes the LH surge

Answer 15

kisspeptin and oestrogen (high levels)

Question 16

high oestrogen expression

Answer 16

ARC kisspeptide inhibited
AVPV kisspeptide neurons are stimulated
overrides negative feedback , increase in GnRH pulse and LH stimulation

Question 17

which receptor provides oestrogen feedback

Answer 17

estrogen receptor -a (in KO no reponse to ovariectomy unlike ER-B)

Question 18

optimal dose of kisspeptide in single subcutaneous injection to stimulate plasma LH

Answer 18

0.4nmol/kg

Question 19

when is the effect of kisspeptin the greatest on LH

Answer 19

prior to ovulation (prepares for LH surge)
kisspeptin triggers oocyte maturation (collect for IVF)

Question 20

IVF steps

Answer 20

administer FSH (grows multiple follicles)
trigger ovulation (releases eggs)
fertilisation of oocyte
replantation

Question 21

other effects of kisspeptin

Answer 21

libido and maturation