Étienne-Émile Baulieu

Neurosteroids

Beginning in the late 1970s, Baulieu and Paul Robel with collaborators investigated the presence and metabolism of steroid hormones in the central nervous system. In a series of studies published between 1978 and 1981, they demonstrated that pregnenolone, dehydroepiandrosterone (DHEA), and related steroids are synthesized de novo in the brain, independently of peripheral endocrine glands. In 1981 Baulieu introduced the term “neurosteroids” to describe these endogenously produced steroids with potential neuromodulatory actions. During the early 1980s Baulieu’s group catalogued the distribution of neurosteroids in different brain regions and documented their variation across age, stress, and physiological states. At that time Baulieu emphasized that, although neurosteroids were clearly present in the nervous system, their physiological function remained unknown.

A major advance occurred in 1986, when Majewska, Harrison, and others reported that allopregnanolone and related neurosteroids are potent positive modulators of the GABAA receptor. This work provided the first molecular mechanism for neurosteroid action and established a direct link between Baulieu’s discovery of brain-derived steroids and inhibitory neurotransmission. Subsequent studies throughout the late 1980s and 1990s expanded the concept of neurosteroid modulation of GABAergic signaling and its relevance to stress, anxiety, seizure susceptibility, and mood regulation.

Baulieu continued to investigate the physiological and clinical significance of DHEA, pregnenolone, and their sulfate esters, including studies on aging, cognition, neuroprotection, and mood. In his 1997 reviews Baulieu summarized the state of knowledge regarding neuroactive neurosteroids.

In the early 21st century, the neurosteroid field developed into a translational research area in neuropsychopharmacology. Synthetic analogues of endogenous neurosteroids were developed as therapeutic agents, including ganaxolone for seizure disorders and zuranolone for postpartum depression and major depressive disorder. Additional neurosteroid-based or neurosteroid-inspired modulators of GABAA receptors have been explored in preclinical and clinical research.

RU486

Baulieu was known worldwide for his work on RU486 (Mifepristone) and has been termed the "father" of the abortion pill. Baulieu, who had identified the progesterone receptor, suggested to Roussel-Uclaf to modify the progesterone molecule to create an anti-progesterone. Georges Teutsch then synthesized an agent that became initially known as RU486 in 1980. Baulieu investigated the actions of this agent as an anti-progesterone steroid that proved to be able to induce early abortion, and became more effective in conjunction with misoprostol. As a proponent of a nonsurgical approach to abortion, Baulieu became an advocate for RU486 even when the company withdrew from the product and propelled him into the limelight of the abortion debate. As an anti-progesterone, RU486 also has other potential such as in the treatment of certain conditions (breast cancer, brain cancer, endometriosis, diabetes, hypertension), and the anti-cortisol activity he discovered may be useful to manage depression or Cushing's syndrome.

Longevity

Baulieu took increasing interest in what he called the "longevity revolution", that people are living longer, and its implications. As part of this, he investigated the potential of hormonal substitution such as DHEA to increase well-being in old age. The "Institute Baulieu" was started in 2008 to address issues that are detrimental to health in older people. One focus of research in the 2020s is finding ways to decrease the problems of the elderly to function independently.