Kei-ichiro Maeda Memorial Ise Award 2021

Basic and applied research on neuroendocrine
control of mammalian reproduction

Okayama University of Science

Sho NAKAMURA

AppliedResearchBasicResearch

Kisspeptin
neurons

Neurokinin BsignalingNeuroendocrine control of reproductive function
Kisspeptin neurons

H ypothalamusP ituitaryG onadalaxis

GnRH neurons

LH surge

LH pulse

Ovulation
GnRH : Gonadotropin-releasing hormone
LH : Luteinizing hormone

Follicular development

Kisspeptin neurons control reproductive function
in mammals.
Wild-typeKiss1 KO

LH surge

Wild-typeKiss1 KO

LH pulse

Wild-typeOvary

Kiss1 KO
Kiss1 KO rat

Uenoyama, Nakamura et al., J Neuroendocinol, 2015

Kisspeptin treatment immediately induced
LH secretion in Kiss1 KO rats.

LH concentration (ng/ml)

Kisspeptin

Kiss1 KO rat-101
Time after injection (h)2Uenoyama, Nakamura et al., J Neuroendocinol, 2015

Kisspeptin neurons control reproductive function
in mammals.
Kisspeptin neurons

GnRH neurons

LH surge

LH pulse

Ovulation
GnRH : Gonadotropin-releasing hormone
LH : Luteinizing hormone

Follicular development

Kisspeptin neurons in the ARC = KNDy neurons

Kisspeptin neurons
Kisspeptin

NKBMerge

Kisspeptin

DynMerge

ARC

Nakamura et al., Theriogenology, 2017

NKB: Neurokinin B
Dyn: Dynorphin A
ARC: Arcuate nucleus

NKB stimulate pulsatile LH secretionby activating KNDy neurons.

NKB receptor

NKB

KNDy neurons
GnRH neurons
LH pulses
NKB: Neurokinin B

Applied research on reproductive function in cattle
using NKB receptor agonist (senktide)Effect of NKB signaling on LH pulses in postpartum cattle
KNDy neurons

Senktide(NKB agonist)

LH pulses

Luteinization

Estrouscycle
Folliculardevelopment
Ovulation

Suckling stimulusSenktide accelerates LH pulses andshortened the days until postpartum first luteinization.
Senktide
30 nmol/min

PlasmaLH (ng/ml)
LH (ng/ml)

LH pulses

10080

PlasmaLH (ng/ml)
LH (ng/ml)

60
40
20010

#1134

#1242

VehB

10-404202428-42#831

Senktide
VehicleSenktide 30 nmol/min
Senktide 300 nmol/min

10

#216

Days to postpartum
first luteinization
60a4004202428300 2428ab

#964

040
4 20 60
247028 -420 -4 30
5080
2Days after
after theparturitionTime
start of infusion (h)Plasma LH (ng/ml)

Animals showing corpus luteum (%)

A2PulseSenktide
300 nmol/min

Postpartum days
to first luteinization
DaysVehicle#1147b20

400

520
Veh 4 30

4Senktide
Nakamura et al., Bio Reprod, 201710

Effect of NKB signaling on LH pulses in postpartum cattle
KNDy neurons

Senktide(NKB agonist)

LH pulses

Luteinization

Estrouscycle
Folliculardevelopment
Ovulation

Suckling stimulusEffects of NKB signaling on core body temperature

Heat stressNKB ?

LH pulses
KNDy neurons

Thermoregulatingneurons

Oocyte quality

Activation of NKB signaling decreased vaginal temperature
in cattle
Vaginal temperature
GnRH

SenktideVehSenktide

Heat-defense
response

RecorderNakamura et al., Domt Ani Endocrinol, 2021

Applied
Research

NKB (senktide)

Activation ofLH pulse inlactating cattle

BasicResearch

KNDy neurons
Essential factor ofreproductive function

Activation ofHeat-defense
responseAcknowledgment
Dr. Kei-ichiro Maeda
Dr. Hiroko Tsukamura
Dr. Yoshihisa Uenoyama
Dr. Naoko Inoue
Dr. Satoshi Ohkura
Dr. Shuichi Matsuyama

Acknowledgment

In front of lab in 2016
Dairy cow farm of Cambodia in 20122017