Modulation of NADPH-diaphorase and glial fibrillary acidic protein by progesterone in astrocytes from normal and injured rat spinal cord

Progesterone (P4) can be synthesized in both central and peripheral nervous system (PNS) and exerts trophic effects in the PNS. To study its potential effects in the spinal cord, we investigated P4 modulation (4 mg/kg/day for 3 days) of two proteins responding to injury: NADPH-diaphorase, an enzyme with nitric oxide synthase activity, and glial fibrillary acidic protein (G FAP), a marker of astrocyte reactivity. The proteins were studied at three levels of the spinal cord from rats with total transection (TRX) at T10: ab ove (T5 level), below (L1 level) and caudal to the lesion (L3 level). Equiv alent regions were dissected in controls. The number and area of NADPH-diap horase active or GFAP immunoreactive astrocytes/0.1 mm(2) in white matter ( lateral funiculus) or gray matter (Lamina IX) was measured by computerized image analysis. In controls, P4 increased the number of GFAP-immoreactive a strocytes in gray and white matter at all levels of the spinal cord, while astrocyte are also increased in white matter throughout and in gray matter at the T5 region. In control rats P4 did not change NADPH-diaphorase activi ty. In rats with TRX and not receiving hormone, a general up-regulation of the number and area of GFAP-positive astrocytes was found at all levels of the spinal cord. In rats with TRX, P4 did not change the already high GFAP- expression. In the TRX group, instead, P4 increased the number and ara of N ADPH-diaphorase active astrocytes in white and gray matter immediately abov e and below, but not caudal to the lesion. Thus, the response of the two pr oteins to P4 was conditioned by environmental factors, in that NADPH-diapho rase activity was hormonally modulated in astrocytes reacting to trauma, wh ereas up-regulation of GFAP by P4 was produced in resting astrocytes from n on-injured animals. (C) 2000 Elsevier Science Ltd. All rights reserved.