Spring is usually synonymous with renewal, revival, re-blooming. Birds are singing, flowers are opening, the sun is shining. It is also the time of year when many animal species engage in reproductive behaviour.
Prof. Jacques Balthazart, Center for Cellular and Molecular Neurobiology at the University of Liège, has devoted the last 35 years to the study of the neuroendocrine and neurochemical processes involved in sexual behaviour. We have been aware for quite some time that estradiol-anovarian steroid that controls female reproduction –is also produced in the brain not only of females, but also of males under the influence of specific enzyme, namely aromatase, which turns androgens such as testosterone into estrogens such as estradiol, Prof Balthazart explains. In a male brain testosterone mostly works at cellular level through the estradiol it produces via aromatisation. The functional significance of such a double production of estradiol (in the ovary and in the brain) is however still insufficiently understood.
From the quail to the mouse
Researchers are interested in anything that can modify behaviour. To this end they observe the effect of sexual hormones in several bird species, notably the quail, a species that is particularly suited for such studies. However, for the last eight years Prof. Balthazart’s colleague Julie Bakker, an FNRS Research Associate qualified researcher, has carried out similar investigations on mice. This gives our research another dimension, Jacques Balthazart comments. Mice are animals whose genome transcription can easily be modified, which yields subjects in which the expression of a specific gene has been suppressed (knock-out or KO animals). This technique that produces genetically modified mice is now a routine part of research. New experiments show that changes in the estrogen concentration in the brain are followed within minutes by changes in the behaviour of male mice. For instance injecting an aromatase inhibitoris followed within ten minutes by an almost complete inhibition of copulatory behaviour, he says. Conversely injecting a large dose of estradiol stimulates within ten minutes the sexual activity of male mice in which aromatase had been genetically switched off (knock-out mice) and abolishes the behavioural inhibition produced by aromatase inhibitors. These data show that estrogens in the brain rapidly modulate behaviour, probably through non genomic processes, the scientist adds. Estradiol would thus become a neuro-modulator or even a neurotransmitter and should be studied as such.
A new window onto brain processesThe latest research at the Liège laboratory happens to show that estrogen production in the brain is rapidly modified by structural changes of the aromatase, which in turn depend on the local activity of neurotransmitters, notably glutamate. Prof. Balthazart’s team has also conclusively shown that the estradiol produced by aromatase in the brain has most if not all the characteristic features of neurotransmitters in the wider sense. The function of this steroid as hormone or neurotransmitter is determined by where synthesis and action take place but also by the local concentration at which it works», Jacques Balthazart concludes. This distinction between the two functions of the same substance could have significant consequences both on the design of future research plans and on the development of clinical interventions involving the use of estrogens in the brain.
Traduction Christine Pagnoulle
The team’s observations on estradiol’s rapid impact on behaviour have been accepted for publication and will soon come out in The Journal of Neuroscience, a research project carried out by Mélanie Taziaux, Matthieu Keller, Julie Bakker, and Jacques Balthazart.