Progesterone: a universal stimulus for neuronal cells?

Abstract

Progesterone: The sexual hormone progesterone is a member of the steroid hormone family, and is the most important representative of the gestagenes sub-group. It plays an elementary role in the female menstruation cycle and is essential for the establishment and the maintenance of a pregnancy, however gestagenes like progesterone are also abundant in males. In 1990, the existence of steroids was described in different cells of the central nervous system (CNS) (Baulieu and Robel, 1990). Up until this point, the effect of sexual hormones on neural cells was rather unknown, other than in the well known regulatory centers of the hypothalamus. Since then the essential enzymes of steroid synthesis, cytochrome P450 side chain cleavage enzyme (P450scc) and 3 β-hydroxysteroid-dehydrogenase (3 β-HSD), have been detected in the central (Mellon et al., 1993) as well as in the peripheral nervous system (Schaeffer et al., 2010). Within the cerebellum Purkinje cells were identified as major sites for neurosteroid formation in the mammalian brain, synthesizing progesterone as well as estradiol (Tsutsui et al., 2011). Traditionally, the effects of progesterone are mediated by genomic mechanisms of classical progesterone receptors which act as transcription factors. Basically, two relevant isoforms, the N-terminal shortened A-form (PR-A, 86 kDa) and the native B-form (PR-B, 110 kDa) are known. Nevertheless, in addition to the genomic signaling pathway, other, non-genomic pathways have been described. The most important member of this non-genomic receptor family seems to be the “progesterone receptor membrane component 1” (PGRMC1). Neural expression of PR-A, PR-B and PGRMC1 could already be proven in different components of the CNS and the peripheral nervous system (PNS) e.g., the hypothalamus, the cerebellum and the dorsal root ganglia (Wessel et al., 2014b).