Effects of progesterone on hyperoxia-induced damage in mouse C8-D1A astrocytes.
BACKGROUND
The birth of most mammals features a dramatic increase in oxygen while placenta-derived hormones such as β-estradiol and progesterone plummet. In experimental newborn animals, transiently elevated oxygen concentrations cause death of neurons, astrocytes, and oligodendrocyte precursors. High oxygen has been associated with cerebral palsy in human preterm infants while progesterone is being used to prevent preterm delivery and investigated as a neuroprotective agent.


METHODS
In this study, we investigated the effects of hyperoxia (80% O2 for 24, 48, and 72 h) on cultured C8-D1A astrocytes in the presence or absence of progesterone at concentrations ranging from 10(-9) to 10(-5) mol/L.


RESULTS
Hyperoxia measured by methytetrazolium assay (MTT) reduced cell viability, increased release of lactate dehydrogenase (LDH), reduced carboxyfluorescein diacetate succinimidyl ester (CFSE)-assessed cell proliferation, and downregulated Cylin D2 expression. Progesterone did not affect any of these hyperoxia-mediated indicators of cell death or malfunctioning. Real-time PCR analysis showed that hyperoxia caused downregulation of the progesterone receptors PR-AB und PR-B.


CONCLUSIONS
Our experiments showed that there was no protective effect of progesterone on hyperoxia-inducted cell damage on mouse C8-D1A astrocytes. Down regulation of the progesterone receptors might be linked to the lack of protective effects.
Department of Neonatology Charité University Medical Center Berlin Germany.
Friederike
F
Weber
Department of Neonatology Charité University Medical Center Berlin Germany.
Stefanie
S
Endesfelder
Department of Neonatology Charité University Medical Center Berlin Germany.
Christoph
C
Bührer
Department of Neonatology Charité University Medical Center Berlin Germany.
Monika
M
Berns
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D018496:Hyperoxia / Q000150:complications* / Q000188:drug therapy*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects; D010100:Oxygen / Q000009:adverse effects / Q000502:physiology; D011374:Progesterone / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000378:metabolism
D018696:Neuroprotective Agents; D011980:Receptors, Progesterone; D011374:Progesterone; D010100:Oxygen
Astrocytes; cell proliferation; hyperoxia; progesterone; progesterone receptor