Abstract
Psychosocial
stress
disrupts
reproduction
and
interferes
with
pulsatile
LH
secretion.
The
posterodorsal
medial
amygdala
(MePD)
is
an
upstream
modulator
of
the
reproductive
axis
stress.
Corticotropin-releasing
factor
type
2
receptors
(CRFR2s)
are
activated
in
presence
psychosocial
together
increased
expression
CRFR2
ligand
Urocortin3
(Ucn3)
MePD
rodents.
We
investigate
whether
Ucn3
signalling
involved
mediating
suppressive
effect
on
pulsatility.
First,
we
administered
into
monitored
pulses
ovariectomized
mice.
Next,
delivered
Astressin2B,
a
selective
antagonist,
intra-MePD
predator
odor,
2,4,5-trimethylthiazole
(TMT)
examined
pulses.
Subsequently,
virally
infected
Ucn3-cre-tdTomato
mice
inhibitory
designer
receptor
exclusively
by
drugs
(DREADDs)
targeting
neurons
while
exposing
to
TMT
or
restraint
pulsatility
as
well
corticosterone
release.
Administration
dose-dependently
inhibited
administration
Astressin2B
blocked
Additionally,
DREADDs
inhibition
stress-induced
These
results
demonstrate
for
first
time
that
mediate
suppression
GnRH
pulse
generator
plays
role
modulating
hypothalamic-pituitary-gonadal
hypothalamic-pituitary-adrenal
axes,
this
brain
locus
may
represent
nodal
center
interaction
between
axes.
Journal of Neuroendocrinology,
Год журнала:
2022,
Номер
34(5)
Опубликована: Янв. 19, 2022
Abstract
The
concept
that
different
systems
control
episodic
and
surge
secretion
of
gonadotropin‐releasing
hormone
(GnRH)
was
well
established
by
the
time
GnRH
identified
formed
framework
for
studies
physiological
roles
GnRH,
later
kisspeptin.
Here,
we
focus
on
recent
identifying
neural
mechanisms
underlying
these
two
modes
secretion,
with
an
emphasis
their
core
components.
There
is
now
compelling
data
kisspeptin
neurons
in
arcuate
nucleus
also
contain
neurokinin
B
(NKB)
dynorphin
(i.e.,
KNDy
cells)
projections
to
dendrons
constitute
pulse
generator
mice
rats.
strong
evidence
a
similar
role
sheep
goats,
weaker
monkeys
humans.
However,
whether
act
and/or
soma
dendrites
are
found
mediobasal
hypothalamus
(MBH)
species
remains
unclear.
components
GnRH/luteinising
consist
endocrine
signal
initiates
process
trigger
drives
during
surge.
In
all
spontaneous
ovulators,
rise
estradiol
from
maturing
follicle(s),
site
estrogen
positive
feedback
being
rostral
periventricular
rodents
MBH
primates.
considerable
variations
trigger,
three
major
classes.
First,
reflex
this
initiated
coitus
carried
or
vascular
pathways.
Second,
rodents,
there
day
originates
suprachiasmatic
activates
dendrites.
Finally,
nitric
oxide‐producing
ventromedial
nucleus,
appear
participate
driving
release
Neurons
in
the
hypothalamic
arcuate
nucleus
(ARC)
that
co-express
kisspeptin,
neurokinin
B
and
dynorphin
(KNDy
cells)
are
essential
for
mammalian
reproduction
as
key
regulators
of
gonadotropin-releasing
hormone
(GnRH)
secretion.
Although
multiple
endogenous
exogenous
signals
act
indirectly
via
KNDy
neurons
to
regulate
GnRH,
identity
upstream
provide
synaptic
input
this
subpopulation
is
unclear.
We
used
rabies-mediated
tract-tracing
transgenic
Kiss1-Cre
mice
combined
with
whole-brain
optical
clearing
multiple-label
immunofluorescence
create
a
comprehensive
quantitative
brain-wide
map
providing
monosynaptic
cells,
well
identify
estrogen
receptor
content
peptidergic
phenotype
afferents.
Over
90%
originated
from
nuclei
both
male
female
mice.
The
greatest
arose
non-KNDy
ARC
neurons,
including
proopiomelanocortin-expressing
cells.
Significant
female-dominant
sex
differences
afferent
were
detected
estrogen-sensitive
critical
reproductive
endocrine
function
sexual
behavior
mice,
indicating
cells
may
unique
site
coordination
sex-specific
gonadotropin
release.
These
data
insight
into
structural
framework
underlying
ability
integrate
environmental
important
regulation
function.
Journal of Neuroendocrinology,
Год журнала:
2020,
Номер
32(6)
Опубликована: Апрель 17, 2020
Somato-dendritic
secretion
was
first
demonstrated
over
30
years
ago.
However,
although
its
existence
has
become
widely
accepted,
the
function
of
somato-dendritic
is
still
not
completely
understood.
Hypothalamic
magnocellular
neurosecretory
cells
were
among
neuronal
phenotypes
in
which
and
are
neurones
for
functions
best
characterised.
These
secrete
neuropeptides,
vasopressin
oxytocin,
an
orthograde
manner
from
their
axons
posterior
pituitary
gland
into
blood
circulation
to
regulate
body
fluid
balance
reproductive
physiology.
Retrograde
oxytocin
modulates
activity
they
secreted,
as
well
neighbouring
populations
neurones,
provide
intra-
inter-population
signals
that
coordinate
endocrine
autonomic
responses
control
peripheral
have
also
been
proposed
act
hormone-like
brain.
There
some
evidence
beyond
local
environment
where
there
no
vasopressin-
or
oxytocin-containing
but,
date,
conclusive
for,
against,
signalling
throughout
brain,
it
difficult
imagine
levels
found
brain
could
be
underpinned
by
release
relatively
sparse
axon
terminal
fields.
The
generation
data
resolve
this
issue
remains
a
priority
field.
Abstract
Polycystic
ovarian
syndrome
(PCOS),
the
most
common
endocrinopathy
affecting
women
worldwide,
is
characterized
by
elevated
luteinizing
hormone
(LH)
pulse
frequency
due
to
impaired
suppression
of
gonadotrophin-releasing
(GnRH)
release
steroid
negative
feedback.
Although
neurons
that
co-express
kisspeptin,
neurokinin
B,
and
dynorphin
(KNDy
cells)
were
recently
defined
as
GnRH/LH
generator,
little
understood
about
their
role
in
pathogenesis
PCOS.
We
used
a
prenatal
androgen-treated
(PNA)
mouse
model
PCOS
determine
whether
changes
KNDy
or
afferent
network
underlie
altered
First,
we
identified
androgen
receptor
gene
expression
cells
PNA
mice,
whereas
progesterone
was
significantly
reduced,
suggesting
androgens
disrupt
feedback
via
direct
actions
upon
cells.
Second,
discovered
GABAergic
glutamatergic
synaptic
input
reduced
mice.
Retrograde
monosynaptic
tract-tracing
revealed
dramatic
reduction
originates
from
sexually
dimorphic
afferents
preoptic
area,
anteroventral
periventricular
nucleus,
anterior
hypothalamic
area
lateral
hypothalamus.
These
results
reveal
2
sites
neuronal
alterations
potentially
responsible
for
defects
PCOS:
within
neurons,
inputs
hormone-responsive
regions.
How
each
these
contribute
neuroendocrine
phenotype
seen
PCOS,
specific
sets
upstream
process,
remains
be
determined.
Journal of Neuroendocrinology,
Год журнала:
2023,
Номер
35(9)
Опубликована: Май 2, 2023
Abstract
Uncovering
the
central
mechanism
underlying
mammalian
reproduction
is
warranted
to
develop
new
therapeutic
approaches
for
reproductive
disorders
in
humans
and
domestic
animals.
The
present
study
focused
on
role
of
arcuate
kisspeptin
neurones
(also
known
as
KNDy
neurones)
an
intrinsic
gonadotropin‐releasing
hormone
(GnRH)
pulse
generator,
which
plays
a
fundamental
via
stimulation
pituitary
gonadotropin
synthesis
release
thereby
gametogenesis
steroidogenesis
gonads
mammals.
We
also
discuss
that
inhibits
pulsatile
GnRH/gonadotropin
under
negative
energy
balance,
considering
often
occur
during
malnutrition
livestock.