Disruption of male sexual behavior in rats by tetrahydrofurandiols (THF-diols)

Leukotoxin Diols from Ground Corncob Bedding Disrupt Estrous Cyclicity in Rats and Stimulate MCF-7 Breast Cancer Cell Proliferation

“…This vehicle has no significant effects on ovarian cyclicity in rats or on male or female sexual behavior relative to tap water controls (Mani et al 2005; Markaverich et al 1988, 2002a, 2002b). On day 31, the cycling female rats were given a 1:1 mixture of the 9,10-dihy-droxy-12-octadecenoic acid [leukotoxin diol (LTX-diol)] isomers (2 μg/mL) in the tap water–Tween 80 vehicle for an additional 30 days.…”

“…Peak I was purified to homogeneity and identified as an isomeric mixture of 9,12-oxy-10,13-dihydroxyocta-decanoic acid and 10,13-oxy-9,12-dihydroxy-octadecanoic acid [tetrahydrofurandiols (THF-diols)] (Markaverich et al 2002a). The compounds (Figure 1) were synthesized and found to stimulate MCF-7 human breast cancer proliferation in vitro and block sexual behavior in male rats (Mani et al 2005) and female rats and ovarian cyclicity (Mani et al 2005; Markaverich et al 2002b) at concentrations approximately 200-fold lower than classical phytoestrogens (Markaverich et al 1995). In addition, the THF-diols are apparently devoid of estrogenic activity and do not bind to the estrogen receptor (ER) or nuclear type II [ 3 H]estradiol binding sites (Markaverich et al 2002a, 2002b).…”

Regulation of the nitric oxide pathway genes by tetrahydrofurandiols: Microarray analysis of MCF-7 human breast cancer cells

“…LTX-diols and THF-diols block sexual behavior and cyclicity in adult female rats [1,5]. Although the THF-diols also block male sexual behavior, LTX-diols apparently lack this biological activity [4]. While the exact mechanism of action of these compounds remains unknown, the regulation of genes in the nitric oxide pathway by THF-diols described by the present studies is consistent with the well-known effects of these compounds on reproductive function [3,4,6] and their mitogenic activities in tumor cells [1,3,8].…”

“…Peak I was identified by gas chromatography-mass spectrometry (GC-MS) as an isomeric mixture of 9,12-oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid (tetrahydrofurandiols, THF-diols). Similar to the corncob extract, synthetic THF-diol stimulated MCF-7 human breast cancer cell proliferation in vitro [1], did not bind ER or the nuclear type II [ 3 H]estradiol binding sites and blocked sexual behavior in male and female rats [4] at a very low dose (~0.30 mg/kg body weight/day). The second mitogenic HPLC peak of mitogenic activity was subsequently identified as 9,10-dihydroxy-12-octadecenoic acid (leukotoxin diol; LTX-diol), a well-known leukotoxin [5].…”

Sexual Behavior: From Hormonal Regulation to Endocrine Disruption

“…By contrast, longer periods of exposure of male mice to BPA increased the times to mounting, intromission and ejaculation, and decreased the numbers of intromissions and thrusts in both naïve and sexually experienced male mice [63]. Similar differences between short- and long-term exposures were observed for corncob bedding and derived tetrahydrofuran-diols [67, 68]. Changes in behavior were also reported for rats subjected to long-term phytoestrogen exposure [69] and NP [70].…”