Progesterone is a well-known
steroid hormone, synthesized by ovaries and placenta in females, and by adrenal glands in both males and females. Several tissues are targets of
progesterone and the nervous system is a major one.
Progesterone is also locally synthesized by the nervous system and qualifies, therefore, as a
neurosteroid. In addition, the nervous system has the capacity to bio-convert
progesterone into its active metabolite
allopregnanolone. The
enzymes required for
progesterone and
allopregnanolone synthesis are widely distributed in brain and spinal cord. Increased local biosynthesis of
pregnenolone,
progesterone and 5α-dihydroprogesterone may be a part of an endogenous neuroprotective mechanism in response to
nervous system injuries.
Progesterone and
allopregnanolone neuroprotective effects have been widely recognized. Multiple receptors or associated
proteins may contribute to the
progesterone effects: classical
nuclear receptors (PR), membrane
progesterone receptor component 1 (PGRMC1), membrane
progesterone receptors (mPR), and γ-
aminobutyric acid type A (GABAA) receptors after conversion to
allopregnanolone. In this review, we will succinctly describe
progesterone and
allopregnanolone biosynthetic pathways and
enzyme distribution in brain and spinal cord. Then, we will summarize our work on
progesterone receptor distribution and cellular expression in brain and spinal cord;
neurosteroid stimulation after
nervous system injuries (
spinal cord injury,
traumatic brain injury, and
stroke); and on
progesterone and
allopregnanolone neuroprotective effects in different experimental models including
stroke and
spinal cord injury. We will discuss in detail the
neuroprotective effects of
progesterone on the nervous system via PR, and of
allopregnanolone via its modulation of GABAA receptors.