Role of kisspeptin in reproduction of ruminants

1. Ajitha kumar H M
Hudedh
Phd scholar
Role of kisspeptin in reproduction of
ruminants

2. Contents
Kisspeptin story.
Biochemistry of Kisspeptin.
Connections and actions of kisspeptin on GnRH neurons.
Action of kisspeptin on reproductive function.
Kisspeptin:- Reproductive researches in ruminants.
Conclusion.

3. Kisspeptin story
Kisspeptin :- Syn. Metastin.
First discovered by Lee et al. In the year of 1996.
Kiss1 gene was named for famous Hershey chocolate Kiss
(Pennsylvania, USA) in the area where the gene was discovered.
(Gottsch et al., 2004)

4. What is kisspeptin
Kisspeptins are peptide products of the KiSS-1 gene.
Kiss-1 gene :-metastasis suppressing gene in malignant
melanoma cells.
The KiSS-1 gene is located on human chromosome 1q32
peptide.
(West et al., 1998)

5. Biochemistry of Kisspeptin
Kisspeptin is peptide hormones contain 145-amino acid peptide.
Produces various lengths (10-54) of biologically active peptide.
Which can be further truncated to 14, 13 or 10 amino acid
carboxyl-terminal fragments.
(Gottschet et al., 2004)

7. localization
Kisspeptin and GPR54 found:-
(Muir et al., 2001)
Brain Hypothalamus, Brainstem,
Spinal cord and Pituitary,
Gonad Ovary and Prostate,
GIT Liver, Pancreas and Intestine,
Pregnancy Umbilical vein and Placenta

8. (ARC)

9.  G protein- coupled receptor (GPR54) is the
strongly cognate receptor of kisspeptin.
(Chaikhun et al., 2001)
In situ hybridization (ISH)
Immunohistochemistry
(IHC)

10. In Ewes
From ISH technique:-
Kiss1 neurons were found in ARC and POA.
Greater cell density in ARC.
From the IHC technique:-
Identified in the ARC, POA and DMN.
(Rometo et al., 2007)

11. (Colledge et al., 2008)

12. Connections and actions of kisspeptin
on GnRH neurons
Kispeptin by
KISS1/ GPR54
Kispeptin by
KISS1/ GPR54 Gq/11
phospholipase C
Inositol
triphosphate (IP3)
Diacylglycerol
(DAG)
couples
activate

13. increase in
intracellular Ca2
DAG
ERK1/2
kinase phosphorylation
protein kinase C

15. DAG stimulates GnRH depolarization.
By activation nonselective cation channel (TRPC).
Inhibition of an inwardly rectifying potassium channel (Kir) .
Important mechanism

16. • Thus kisspeptins act directly on GnRH neurons to induce a
sustained depolarization event and increase the rate of action
potential firing.
(Zhang et al., 2008)
• The ability of GnRH neurons to respond to kisspeptin
signals is progressively regulated.
25% in the pre-
pubertal period
90%in adults
Cont….

17. • GABA has a predominantly hyperpolarizing effect on GnRH
neurons to inhibit GnRH release
• Kisspeptins have been reported to suppress the inhibitory effects
of GABA receptor signaling in GnRH neurons
(Castellano et al., 2006)
Action of kisspeptin

18. Action of kisspeptin on reproductive function
Kisspeptin and puberty:
• In mammals kisspeptin and GPR54 were key regulators of
puberty due to the programmed increased in Kiss1 mRNA,
GPR54 mRNA
• The AVPV POA, and the ARC areas which could in turn
cause an increase in GPR54 sensitivity to kisspeptin

19. Activation of the kisspeptin
Increased
pulsatile
modes of
GnRH
Surge
modes of
GnRH
In the POA and the ME, the GnRH will release by surge
mode.

20. Kisspeptin mechanism on hypothalamic pituitary
gonadal axis
It is well known that steroid hormones fluctuate across the
female estrous cycle and feedback from gonads regulates the HPG axis.
feedback effects on the GnRH neuron (Hashizume et al., 2010).
.
Kisspeptin neurons
express
Androgen receptor (AR)
Progesterone receptor (PR)
Estrogen receptor α (ERα)

21. THE MODEL IS MOST WELL-DEVELOPED
IN RODENTS.
the Kiss1 neurons in the AVPV are directly stimulated by estrogen

22. kisspeptin cells in the ARC are held steady to play a role in the
negative feedback control of GnRH/LH secretion

23. Three types of estrogen feedback important for
GnRH releasing in ewes:
Short-
term
negative
Long-term
negative
feedback
Transient
positive
feedback
(Smith et al., 2009)

25. KISSPEPTIN: REPRODUCTIVE
RESEARCHES IN RUMINANTS
CATTLE:-
 In cattle, kisspeptin not only stimulates lutenizing
hormones (LH) but also growth hormones (GH) in OVX
cows.
 Shown by injecting kisspeptin10 (Kp10) in different doses.
 0.13 μg/kg body weight (5animals).
(Hashizume et al., 2010)

26. CONT.
 kisspeptin10 treatment stimulate LH secretion
from anterior pituitary cells in bovines.
(Ezzat et al., 2010)
 In vitro research indicate that kisspeptin was
relevant to the release of GH and PRL as well as
the release of gonadotropin in ruminants.
(Hashizume et al., 2010)

28. In OVX goats,
 Another study found that kisspeptin will not stimulate GH
and PRL releasing during the luteal phase in female goats.
(Tanaka et al., 2012)
Kp10 GnRH
LH
FSH

29. CONCLUSION
 KISSPEPTIN has very important role in the reproduction.
 Kiss1 genes mainly appear in the hypothalamus of
ruminants.
 provide the negative and positive feedback regulation of
GnRH secretion by gonadal steroids.

30. CONT…
 In ewes:- The kisspeptin cells are present in the ARC
play a role in the steroid negative feedback control of
GnRH.
 The kisspeptin cells in the mediodorsal hypothalamus
are involved in the surge mode of release of GnRH.
 Kisspeptin expression is increased immediately before
the preovulatory GnRH/LH surge.

31. Unanswerd questions
The regulation and function of the kisspeptin cells in
the POA area is still not understood further studies
need to be done.

32. Thank you