SUMMARYBackground: Preliminary clinical and experimental results suggest that iron can modify hepatocytes' insulin sensitivity by interfering with insulin receptor and intracellular insulin signalling. Aim: To evaluate in vivo the influence of iron on insulin resistance and insulin release in patients with nonalcoholic fatty liver disease and in vitro the interaction between iron and insulin sensitivity by analysing the effect of iron manipulation on insulin receptor expression in hepatoblastoma HepG2 cell line. Results: Insulin resistance evaluated by homeostatis model assessment (HOMA)-insulin resistance signifi-

Male mice actively direct their urine at nearby females, and this urine reliably contains unconjugated oestradiol (E 2 ) and other steroids. Giving inseminated females minute doses of exogenous E 2 , either systemically or intranasally, can cause failure of blastocyst implantation. Giving juvenile females minute doses of exogenous E 2 promotes measures of reproductive maturity such as uterine mass. Here we show that tritium-labelled E 2 ( 3 H-E 2 ) can be traced from injection into novel male mice to tissues of cohabiting inseminated and juvenile females. We show the presence of 3 H-E 2 in male excretions, transmission to the circulation of females and arrival in the female reproductive tract. In males, 3 H-E 2 given systemically was readily found in reproductive tissues and was especially abundant in bladder urine. In females, 3 H-E 2 was found to enter the system via both nasal and percutaneous routes, and was measurable in the uterus and other tissues. As supraoptimal E 2 levels can both interfere with blastocyst implantation in inseminated females and promote uterine growth in juvenile females, we suggest that absorption of male-excreted E 2 can account for major aspects of the Bruce and Vandenbergh effects.

Male mouse urine contains 17b-oestradiol (E 2 ) and other steroids. Given that males actively direct urine at proximate females and intrauterine implantation of blastocysts is vulnerable to minute amounts of exogenous oestrogens, males' capacity to disrupt early pregnancy could be mediated by steroids in their urine. When male mice were implanted with osmotic pumps containing tritium-labelled E 2 ( 3 H-E 2 ) or injected i.p. with 3 H-E 2 , radioactivity was reliably detected in their urine. Following intranasal administration of 3 H-E 2 to inseminated females, radioactivity was detected in diverse tissue samples, with there being significantly more in reproductive tissues than in brain tissues. When urine was taken from males injected with 3 H-E 2 , and then intranasally administered to inseminated females, radioactivity was detected in the uterus, olfactory bulbs, and mesencephalon and diencephalon (MCCDC). When inseminated and ovariectomised females were perfused at the point of killing to remove blood from tissues, more radioactivity was detected in the uterus than in muscle, olfactory bulbs, MCCDC and cerebral cortex. Pre-treatment with unlabelled E 2 significantly reduced the uptake of 3 H-E 2 in the uterus. Taken with evidence that males deliver their urine to the nasal area of females, these results indicate that male urinary E 2 arrives in tissues, including the uterus, where it could lead to the disruption of blastocyst implantation.

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