Discovery at Development and plasticity in neuroendocrine brain (© Cimino et al, Nature Communications, 2016)

Novel Role for Anti-Müllerian Hormone in the Regulation of GnRH Neuron Excitability and Hormone Secretion

Irene Cimino, Filippo Casoni, Xinhuai Liu, Andrea Messina, Jyoti Parkash, Soazik P Jamin, Sophie Catteau-Jonard, Francis Collier, Marc Baroncini, Didier Dewailly, Pascal Pigny, Mel Prescott, Rebecca Campbell, Allan E Herbison, Vincent Prevot, Paolo Giacobini

Nature Communications 2016 DOI: 10.1038/ncomms10055.

Reproduction in mammals is dependent on specific neurons secreting the neuropeptide Gonadotropin Hormone-Releasing Hormone (GnRH). A number of reproductive disorders in humans are associated with disruption of either GnRH neuronal development or of the normal GnRH secretion. Polycystic Ovary Syndrome (PCOS) is the most common human reproductive disorder, affecting up to 10% of women. Infertility treatments of PCOS women have heterogeneous and limited success, and alternative and more efficient treatments are needed.

In patients with PCOS, Anti-Mullerian Hormone (AMH) levels are elevated and so is the Luteinizing Hormone (LH), whose secretion from the pituitary is under the control of GnRH neurons. Nevertheless, so far this disease has been considered mainly as a gonadal pathology and possible higher regulations from the central nervous system or interactions with it have not been investigated. In particular, studies regarding the possible extra-ovarian effects of AMH on the hypothalamic-pituitary-gonadal axis are currently lacking.

Recently, the research group directed by Dr. Paolo Giacobini (Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, Inserm U1172, Lille; University of Lille) in collaboration with the team of Prof. Allan Herbison (University of Otago School of Medical Sciences, Dunedin, New Zealand) discovered that a significant subset of GnRH-1 neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuronal activity in mice. The use of mouse models and in vitro cell cultures showed that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons.

These findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS.