Progesterone reverses 17β‐estradiol‐mediated neuroprotection and BDNF induction in cultured hippocampal slices

Abstract

Due to the many similarities in mechanisms of action, targets and effects, progesterone, estrogen and neurotrophins have been implicated in synaptic plasticity as well as in neuroprotection and neurodegeneration. In this study, we examined the interactions between 17-β-estradiol (E2) and progesterone (P4) and BDNF on both plasticity and excitotoxicity in rat cultured hippocampal slices. First, we evaluated the neuroprotective effects of E2 and P4 against NMDA toxicity in cultured rat hippocampal slices. As previously reported, pretreatment with 10 nM E2 (24 h) was neuroprotective against NMDA toxicity. However, progesterone (10 nM) added 20 h after E2 treatment for 4 h, reversed its protective effect. In addition, the same E2 treatment resulted in an increase in BDNF protein levels as well as in activation of its receptor, TrkB, while addition of P4 attenuated E2-mediated increase in BDNF and TrkB levels. Furthermore, E2-mediated neuroprotection was eliminated by a BDNF scavenger, TrkB-Fc. Our results indicate that E2 neuroprotective effects are mediated through the BDNF pathway, and that, under certain conditions, P4 antagonizes the protective effect of estrogen.

The regulation of ciliary beat frequency by ovarian steroids in the guinea pig Fallopian tube: interactions between oestradiol and progesterone

“…Moreover, the effects of endogenous PRG were not detected in guinea pigs that were treated with a high dose of βE 2 B (15). These results suggest that βE 2 antagonizes the effects of PRG on CBF in the fimbria. Some reports have shown that PRG signaling antagonizes or interacts with βE 2 signaling.…”

“…The beating cilia of the Fallopian tube in guinea pigs at 4 weeks of age are unlikely to be affected by βE 2 and PRG, because the ovulation starts at 8 weeks of age in guinea pigs. In the fimbria from 4-week-old guinea pigs, CBF was high (17.8 ± 0.2 Hz, n = 3) (Fig.…”

“…1). Our previous report (15) showed that CBF in the fimbria of 12-16-week-old guinea pigs varies from 12 Hz to 16 Hz depending on the phases of the ovarian cycle and that an increase in the plasma concentration of βE 2 or PRG decreases CBF. In the present study, CBF in the fimbriae of 12-16-week-old guinea was highly variable in the absence of exogenous βE 2 B or mPRG (marked by the "↓" in Fig.…”

“…A series of experiments, such as an injection with 3.2 mg/kg/day of βE 2 B, were performed at intervals of at least 3 or 4 days using 3-4 animals. Without any drug administration, the CBF measured at 3-4 day intervals can vary due to the changes in the concentrations of βE 2 and PRG that are endogenously secreted at various phases during the ovarian cycle (15). However, injecting characteristic CBF corresponding to each phase in the ovarian cycle can be mimicked by the in vivo administration of βE 2 benzoate (βE 2 B) or medroxy-PRG (mPRG) (15).…”

“…The ciliary beat frequency (CBF) of the ciliary cells (in the fimbrial region of the Fallopian tube) undergoes cyclic fluctuations that depend on the stages of the ovarian cycle. These cyclic changes in CBF are controlled by the concentrations of β-oestradiol (βE 2 ) and progesterone (PRG), both of which fluctuate throughout the ovarian cycle (15). A performed at 37°C.…”