The term "neurosteroid" refers to both classic and unique steroid molecules
that are synthesized from cholesterol (C) by the central and peripheral ne
rvous systems of higher vertebrates. Therein, they accumulate and modulate
nervous activity by a variety of mechanisms other than the classic steroid
receptor-mediated modulation of genomic activity, although such may also be
involved. Since the insect nervous system expresses ecdysteroid receptors
and responds both directly and developmentally to ecdysteroids, the possibi
lity of ecdysteroidogenesis in the pupal and adult central and peripheral n
ervous system of Manduca sexta and the nervous system of Drosophila melanog
aster larvae was investigated. The endogenous concentrations of the critica
l, dietary-derived Delta(5,7)-sterols ergosterol and 7-dehydrocholesterol (
7dC) remained 10 to 20-fold higher in the Manduca pupal and adult nervous t
issues than was found in the larval hemolymph at the cessation of feeding.
In addition, it was determined that the Manduca pupal nervous system, but n
ot that of the adult, could synthesize H-3/C-14-7dC or H-3-7-dehydro-25-hyd
roxycholesterol (H-3-7d25C) from H-3/C-14-cholesterol (H-3/C-14-C) Or the p
olar sterol substrate H-3-25-hydroxycholesterol (H-3-25C), respectively. Ho
wever, none of the nervous system samples from the two species and the seve
ral stages analyzed, a small window of neural development in these insects,
were capable of incorporating any of the above tracer precursor sterols in
to a radiolabelled ecdysteroid, i.e. less than 0.0005%. Thus, the absence o
f neurosteroidogenesis by the insect nervous system stands in sharp contras
t to previously described nervous system steroid hormone biosynthesis by th
e mammalian nervous system. (C) 1999 Elsevier Science Ltd. All rights reser
ved.