Download Fertility disorders: a regulator in the brain. Press release, September

Paris, 6 September 2011
Press release
Fertility disorders: a regulator in the brain
Several million couples worldwide are affected by infertility; in Europe, experts predict that
this number will double within the next ten years. A new player that controls fertility has
just been identified, which, if it fails, inevitably causes delayed puberty or hypofertility in
animals. This is the conclusion reached by Vincent Prévot, a researcher at Inserm, and his
colleagues at Unit 837 - Jean Pierre Aubert Research Centre (Inserm / Université Lille 2 Droit
et Santé). It appears that prostaglandin E2, a hormone released by glial cells1 in the
neuronal environment is an essential trigger for the entire cascade of events that activate
reproductive functions. This research, published on 5 September 2011 in PNAS, may be the
first step toward developing treatments for fertility disorders originating in the central
nervous system (amenorrhea resulting from an abnormality in the hypothalamus, delayed
puberty, precocious puberty).
The reproductive function is determined by events that take place in the brain. During puberty, a
handful of highly specialised neurons (GnRH neurons), located in the hypothalamus, is activated,
leading to the pulsatile secretion of gonadoliberin or GnRH (Gonadotropin Releasing Hormone).
GnRH secretion stimulates synthesis and release of luteinising hormone (LH) and folliclestimulating hormone (FSH). These hormones are then released into systemic circulation to
promote the growth of the secondary sexual organs during puberty. They then continue to function
throughout life to perform the reproductive function.
Brain
Neurons, glial cells
Hypothalamus
GnRH neurons
Retroaction of
Gonadal
Steroids
Hypophysis
LH, FSH
Ovaries
Oestrogens
Progesterone
Puberty
(acquisition of reproductive function
and secondary sexual characteristics)
Fertility
1
There are ten times more glial cells than neurons. They fill the spaces between neurons, are in contact with blood
vessels and form the myelin sheath that protects certain neurons. We now know that they play a key role in the genesis,
propagation and processing of nerve cell information.
For some years now, the researchers believed that GnRH neurons, in order to function, received
information from neurons located in their immediate environment. Activating these neighbouring
neurons is the trigger for increased GnRH secretion, required for the onset of puberty and for
fertility.
Vincent Prévot, a researcher at Inserm, and his colleagues have just demonstrated that the release
of a hormone (prostaglandin E2, or PGE2) by the glial cells plays an essential role in the electrical
activity of GnRH neurons. Activation of the latter not only depends on the electrical activity of other
neurons, but also on a hormone that is present in the neurons’ glial environment.
Essential dialogue between glial cells and neurons
PGE2 located in the glial cells (astrocytes) has a powerful effect on stimulating the electrical
activity of the GnRH neurons studied by the researchers. Inversely, this electrical activity is
interrupted if PGE2 synthesis is inhibited. In an animal with delayed puberty, where astrocytes
secrete less PGE2, the GnRH neurons have no measurable electrical activity. Adding PGE2 to the
environment restores the neurons’ electrical activity and the reproductive function. A new player
that controls fertility has now been identified, which, if it fails, unfailingly causes delayed puberty or
hypofertility in animals. According to Vincent Prévot, “In addition to revealing that the glial cells play
a primordial role in controlling a major biological function in mammals, the identification of this
hormone opens up new therapeutic possibilities for treating fertility disorders.”
For more details:
Source
Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH)
neuron firing via EP2 receptor activation
Jerome Clasadontea,b,c, Pierre Poulaina,b,c, Naresh K. Hanchatea,b,c, Gabriel Corfasd,e,f, Sergio R. Ojedag,and
Vincent Prevota,b,c
a Institut National de la Santé et de la Recherche Médicale, Jean-Pierre Aubert Research Center, U837,
Development and Plasticity of the Postnatal Brain, F-59000 Lille, France
bUnivérsité Lille Nord de France, F-59000 Lille, France
c UDSL, School of Medicine, F-59000 Lille, France
d F. M. Kirby Neurobiology Center, Children’s Hospital Boston, Boston, MA 02115;
e Departments of Neurology and
fOtology and Laryngology, Harvard Medical School, Boston, MA 02115, USA
gDivision of Neuroscience, Oregon National Primate Research Center/Oregon Health and Science
University, Beaverton, OR 97006, USA
Research contact
Vincent Prevot
Inserm Unit 837 "Centre de recherche Jean Pierre Aubert"
Tel: +33 (0)3-20-62-20-64 / +33 (0)6-12-90-38-76
Email: [email protected]