Po gene expression is modulated by androgens in the sciatic nerve of adult male rats.
The present results show that androgens are able to modulate the Po gene expression in different models. In particular, we have shown that: (1) the messenger for the androgen receptor (AR) is present in the rat sciatic nerve but not in cultured Schwann cells; (2) castration induces a decrease of Po mRNA levels in the sciatic nerve of male rats, which is counteract by the subsequent treatment with dihydrotestosterone (DHT), the 5alpha-reduced metabolite of testosterone; (3) castration is also able to significantly decrease in the sciatic nerve the activity of the enzyme 5alpha-reductase (which converts testosterone into DHT); and (4) DHT is able to stimulate Po gene expression in cultured Schwann cells. These observations seem to indicate that androgens may exert their effect on Po gene expression via indirect mechanisms; modulation of neuronal influences reaching the Schwann cells through the binding of the androgen to the AR present in neurons may be postulated. However, alternative mechanisms may also be taken in consideration. The data presented suggest indeed that androgens might act on Schwann cells via the progesterone receptor (PR) rather than the AR. It has been observed that: (1) the messenger for PR is present in Schwann cells; (2) DHT may activate the transcriptional activity of a PR-responsive gene by binding to the PR; and (3) putative steroid responsive elements have been described in this paper to be present in the Po promoter region.
Magnaghi
V
V
Department of Endocrinology, University of Milan, Via G. Balzaretti 9, 20133, Milan, Italy.
Cavarretta
I
I
Zucchi
I
I
Susani
L
L
Rupprecht
R
R
Hermann
B
B
Martini
L
L
Melcangi
R C
RC
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D018993:Myelin P0 Protein / Q000096:biosynthesis* / Q000235:genetics; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013379:Substrate Specificity; D013739:Testosterone / Q000494:pharmacology*
D018993:Myelin P0 Protein; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase