Although progesterone is a steroid hormone mainly associated with female reproductive functions, such as uterine receptivity and maintenance of pregnancy, accumulating data have shown its physiological actions to extend to several non-reproductive functions in the central nervous system (CNS) both in males and females. In fact, progesterone is de novo synthesized in specific brain regions by neurons and glial cells and is involved in the regulation of various molecular and cellular processes underlying myelination, neuroprotection, neuromodulation, learning and memory, and mood. Furthermore, progesterone has been reported to be implicated in critical developmental events, such as cell differentiation and neural circuits formation. This view is supported by the increase in progesterone synthesis observed during pregnancy in both the placenta and the fetal brain. In the present review, we will focus on progesterone actions during CNS development.

Perinatal exposure to bisphenol A (BPA) in murine models has been reported to affect social behavior and increase anxiety. However, there is little information about the effects of BPA exposure during puberty, a period in which sex hormones influence the maturation and differentiation of the brain. In this work, we evaluated the effect of BPA administration during the juvenile stage (PND 21–50) on anxiety in male and female rats. Newly weaned Wistar rats were treated with BPA (0, 50, or 500 µg/kg/day) for 30 days. To compare the intra- and inter-sex behavioral profiles, rats were evaluated using four different anxiety models: the Open field test (OFT), the Elevated plus maze (EPM), the Light-dark box test (LDBT), and the Defensive burying test (DBT). Males exhibited a clear-cut anxious profile at both doses in all four tests, while no clear behavioral effect of BPA exposure was observed in female rats. The latter showed an altered estrous cycle that initiated earlier in life and had a shorter duration, with the estrous phase predominating. Moreover, the expression of ESR1, ESR2, GABRA1, GRIN1, GR, MR, and AR genes increased in the hippocampus and hypothalamus of male rats treated with 50 µg/kg, but not in females. Our results indicate that BPA consistently induces a higher anxiety profile in male than in female rats, as evidenced predominantly by an increase in passive-coping behaviors and changes in brain gene expression, highlighting the importance of sex in peripubertal behavioral toxicology studies.

Nine cytotoxic [5/7] and [6/6] benzannulated steroid spiroketals were synthesized by palladium catalyzed spiroketalization of 5α and 5β-alkynediols derived from testosterone, diosgenin and cholesterol.

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). These cells arise during the embryonic development by the specification of the neural stem cells to oligodendroglial progenitor cells (OPC); newly formed OPC proliferate, migrate, differentiate, and mature to myelinating oligodendrocytes in the perinatal period. It is known that progesterone promotes the proliferation and differentiation of OPC in early postnatal life through the activation of the intracellular progesterone receptor (PR). Progesterone supports nerve myelination after spinal cord injury in adults. However, the role of progesterone in embryonic OPC differentiation as well as the specific PR isoform involved in progesterone actions in these cells is unknown. By using primary cultures obtained from the embryonic mouse spinal cord, we showed that embryonic OPC expresses both PR-A and PR-B isoforms. We found that progesterone increases the proliferation, differentiation, and myelination potential of embryonic OPC through its PR by upregulating the expression of oligodendroglial genes such as neuron/glia antigen 2 (NG2), sex determining region Y-box9 (SOX9), myelin basic protein (MBP), 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP1), and NK6 homeobox 1 (NKX 6.1). These effects are likely mediated by PR-B, as they are blocked by the silencing of this isoform. The results suggest that progesterone contributes to the process of oligodendrogenesis during prenatal life through specific activation of PR-B.