Subj: [detox] Re: organophosphate pesticides inhibit testosterone
Date: 4/24/2004 12:28:28 PM Eastern Daylight Time


>Can anyone explain what this means in English please. Is this permanent?

It is very poorly written but I think it means that chlorpyrifos and the other
two tested organophosphate pesticides inhibit the metabolism of testosterone by
as much as 98%. Some of the implications: this alone could account for the
recent weight gain in the U.S. population because testosterone is one factor in
regulating weight for both men and women. It could also account for the
commercial success of Viagra.

I don't know if the organophosphate exposure results in permanent effects but I
suspect that a true detox program would reverse at least some of the deficiency
in testosterone metabolism. A 24 hour urine test would be the only reliable
test for testosterone metabolism (as opposed to merely the presence of
testosterone). After some detox work, testosterone supplements may help to
somewhat relieve the effects.
~~~~~~~~~~~~

--- In detox@yahoogroups.com, cherielj@a... wrote:
>
> 1: Drug Metab Dispos. 2003 Apr;31(4):384-91. Related
Articles,Links
>
> Inhibition and activation of the human liver microsomal and human
cytochrome
> P450 3A4 metabolism of testosterone by deployment-related
chemicals.
>
> Usmani KA, Rose RL, Hodgson E.
>
> Department of Environmental and Molecular Toxicology, North
Carolina State
> University, Raleigh, NC 27695, USA.
>
> Cytochrome P450 (P450) enzymes are major catalysts involved in the
metabolism
> of xenobiotics and endogenous substrates such as testosterone
(TST). Major
> TST metabolites formed by human liver microsomes include
> 6beta-hydroxytestosterone (6beta-OHTST), 2beta-hydroxytestosterone
(2beta-OHTST), and
> 15beta-hydroxytestosterone (15beta-OHTST). A screen of 16 cDNA-
expressed human P450 isoforms
> demonstrated that 94% of all TST metabolites are produced by
members of the
> CYP3A subfamily with 6beta-OHTST accounting for 86% of all TST
metabolites.
> Similar K(m) values were observed for production of 6beta-, 2beta-
, and
> 15beta-OHTST with human liver microsomes (HLM) and CYP3A4.
However, V(max) and CL(int)
> were significantly higher for 6beta-OHTST than 2beta-OHTST
(approximately
> 18-fold) and 15beta-OHTST (approximately 40-fold). Preincubation
of HLM with a
> variety of ligands, including chemicals used in military
deployments, resulted in
> varying levels of inhibition or activation of TST metabolism. The
greatest
> inhibition of TST metabolism in HLM was following preincubation
with
> organophosphorus compounds, including chlorpyrifos, phorate, and
fonofos, with up to 80%
> inhibition noticed for several metabolites including 6beta-OHTST.
Preincubation
> of CYP3A4 with chlorpyrifos, but not chlorpyrifos-oxon, resulted
in 98%
> inhibition of TST metabolism. Phorate and fonofos also inhibited
the production of
> most primary metabolites of CYP3A4. Kinetic analysis indicated
that
> chlorpyrifos was one of the most potent inhibitors of major TST
metabolites followed by
> fonofos and phorate. Chlorpyrifos, fonofos, and phorate inhibited
major TST
> metabolites noncompetitively and irreversibly. Conversely,
preincubation of
> CYP3A4 with pyridostigmine bromide increased metabolite levels of
6beta-OHTST and
> 2beta-OHTST. Preincubation of human aromatase (CYP19) with the
test chemicals
> had no effect on the production of the endogenous estrogen, 17beta-
estradiol.
>
> PMID: 12642463 [PubMed - indexed for MEDLINE]