Progesterone derivatives are able to influence peripheral myelin protein 22 and P-0 gene expression: Possible mechanisms of action

The present study has analyzed the effect of progesterone and its derivativ es (dihydroprogesterone and tetrahydroprogesterone) on the gene expression of the peripheral myelin protein 22 utilizing in vivo and in vitro models, The data obtained indicate that tetrahydroprogesterone is able to stimulate the gene expression of peripheral myelin protein 22 both in vivo (in adult but not in old animals) and in Schwann cell cultures. An effect of this st eroid, which is known to interact with the GABA(A) receptor, would not be s urprising, since in the present study we show the presence in Schwann cells and in the sciatic nerve of the messengers for several subunits (alpha 2, alpha 3, beta 1, beta 2, and beta 3) of the GABA(A) receptor. An effect of tetrahydroprogesterone is also evident on the gene expression of another my elin protein, the peripheral myelin protein zero. However, in this case als o dihydroprogesterone, which is able to bind the progesterone receptor, is involved, both in old and adult animals, in the stimulation of messengers l evels of this myelin protein, In conclusion, the present data show that the gene expression of two important peripheral myelin proteins can be influen ced by progesterone derivatives. The hypothesis has been put forward that p art of their effects might occur not through the classical progesterone rec eptor, but rather via an interaction with the GABA(A) receptor. J. Neurosci , Res. 56:349-357, 1999, (C) 1999 Wiley-Liss, Inc.