Revisiting the roles of progesterone and allopregnanolonbe in th nervous system: Resurgence of the progesterone receptors

MICHAEL SCHUMACHER; MATTERN C; ABDEL GHOUMARI; JP OUDINET; PHILLIPE LIERE; FLORENCIA LABOMBARDA; REGINE SITRUK-WARE; ALEJANDRO F. DE NICOLA; RACHIDA GUENNOUN

PROGRESS IN NEUROBIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014 vol. 113 p. 6 - 39

0301-0082

Progesterone is commonly considered as a female reproductive hormone and is well-known for its rolein pregnancy. It is less well appreciated that progesterone and its metabolite allopregnanolone are alsomale hormones, as they are produced in both sexes by the adrenal glands. In addition, they aresynthesized within the nervous system. Progesterone and allopregnanolone are associated withadaptation to stress, and increased production of progesterone within the brain may be part of theresponse of neural cells to injury. Progesterone receptors (PR) are widely distributed throughout thebrain, but their study has been mainly limited to the hypothalamus and reproductive functions, and theextra-hypothalamic receptors have been neglected. This lack of information about brain functions of PRis unexpected, as the protective and trophic effects of progesterone are much investigated, and as thetherapeutic potential of progesterone as a neuroprotective and promyelinating agent is currently beingassessed in clinical trials. The little attention devoted to the brain functions of PR may relate to the widelyaccepted assumption that non-reproductive actions of progesterone may be mainly mediated byallopregnanolone, which does not bind to PR, but acts as a potent positive modulator of g-aminobutyricacid type A (GABAA) receptors. The aim of this review is to critically discuss effects of progesterone on thenervous system via PR, and of allopregnanolone via its modulation of GABAA receptors, with main focuson the brain