Abstract
Triptolide (CAS 38748-32-2), a major active component of Tripterygium wilfordii Hook F (TWHF), was reported to be sex-dependently metabolized mainly due to sex-related
expression of CYP3A2. Sexual dimorphism in the expression of CYP isoforms is affected
by sex difference in daily rhythm of growth hormone (GH) secretion. Neonatal administration
of monosodium glutamate (MSG) can produce latent developmental defects in GH secretion
and associated sex-dependent hepatic enzymes. In the present study, the triptolide
metabolism, CYP3A2 expression and CYP3A-dependent activity were evaluated in Sprague-Dawley
rats treated neonatally with MSG (4 mg/g) or saline (control) on postnatal days 1,
3, 5, 7 and 9. Treatment with MSG during the neonatal period in both sexes caused
a number of disorders characterized by stunted body growth, notable obesity and suppression
of GH secretion to barely detectable levels. In addition, neonatal treatment with
MSG nearly eliminated the male-specific CYP3A2 expression and significantly reduced
the microsomal erythromycin N-demethylation activity in males, while having no effects
on CYP3A2 protein in females. Consistent with the P450 findings, the sexual dimorphism
of triptolide metabolism completely disappeared in MSG-treated rats. This suggested
that neonatal MSG treatment could eliminate the sex-dependent difference in metabolism
of triptolide by suppressing CYP3A2 expression and activity in males to the same extent
as females.
Key words
CAS 38748-32-2 - CYP3A2 - Growth hormone - Monosodium glutamate - Sexual dimorphism
- Triptolide, metabolism
