Uranium, the newest 'hormone'

From New Orleans, at the e.hormone 2004 conference

The incidence of several cancers is especially high on the Four Corners Navajo Reservation, which straddles the Arizona New Mexico border. Because the region hosts more than 2,000 abandoned uranium mines, many of which release dust into the air and water, area researchers wondered whether mine pollution might partially explain the high rate of reproductive-organ cancers in teenage Navajo girls a rate 17 times that of U.S. girls generally.

New animal studies led by Cheryl A. Dyer and Stefanie R. Whish of Northern Arizona University in Flagstaff support that suspicion.

The researchers exposed young female mice to a soluble form of uranium similar to what enters groundwater from mines. To limit the animals' production of natural estrogens, the researchers removed the ovaries the hormones' main source from all the mice in the study. Estrogens are known to be a leading cause of many reproductive cancers.

For 1 month, most mice received drinking water laced with uranium or diethylstilbestrol (DES), an estrogen-mimicking drug. Concentrations of the uranium were half the amount that the Environmental Protection Agency permits in drinking water and roughly one-tenth the concentration found in some water wells on the reservation.

Mice getting DES- or uranium-treated water showed classic markers of heavy estrogen exposure, but mice receiving plain water didn't, Whish notes. In animals drinking the spiked water, for instance, the external opening of the vagina developed early, cells lining the vagina were bigger than normal and exhibited protein changes akin to those that produce nails and corns, and the uterus weighed significantly more than normal. In related test-tube experiments, uranium exposure increased the proliferation of breast-cancer cells, just as estrogen does.

None of these changes accompanied uranium exposure if the animals also received injections of a chemical that blocks estrogen's access to cells. This evidence strongly suggests that "uranium is acting as an estrogen," says Whish.

References:

Whish, S.R. . . . and C.A. Dyer. 2004. Uranyl nitrate mimics estrogen activity in vivo in in vitro. e.hormone 2004 conference. Oct. 27-30. New Orleans.

Pollutants shape baby-gator gonads

Janet Raloff

From New Orleans, at the e.hormone 2003 Conference

Over the past decade, comparisons of alligators from two Florida lakes the relatively pristine Woodruff and the pesticide-laden Apopka have turned up numerous reproductive impairments in the Apopka animals. Low hatching rates, abnormal sex-hormone concentrations, perturbed egg production, and shorter-than-usual penises, are among the effects observed over the years (SN: 7/15/95, p. 44).

These impacts in Lake Apopka's animals had been chronicled only in adolescent and adult gators. Biologists at the University of Florida in Gainesville wanted to see whether the changes occur even in baby gators. So, Teresa Bryan and her coworkers collected 150 alligator eggs from nests on Lake Woodruff and incubated many of them in water laced with nine hormone-mimicking pesticides typical of Lake Apopka. Those include DDT, dieldrin, toxaphene, heptachlor, and alpha-chlordane.

To the researchers' surprise, the pollutants left year-old male gators the developmental equivalent of human toddlers with bigger-than-normal phalluses, not smaller ones.

Bryan studied males and females, which both develop phallus-shaped sex organs. Untreated baby males and those getting a half-strength recipe of the pollutants had phalluses about 3.2 millimeters long 0.4 mm shorter than those in males incubated in the full-strength mix of pesticides. Exposure to the pollutants didn't affect lengths of the baby female's organ called the clitero-phallus, although part of the organ was wider in animals getting the full-strength mix.

Bryan now suspects that the babies process the pollutants differently than older animals do. In the youngest gators, she says, "the contaminants are acting as [excess] androgens."

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References:

Bryan, T., M.R. Milnes, and L.J. Guillette Jr. 2003. Phallic size variation in yearling alligators exposed to naturally occurring environmental contaminants. e.hormone 2003 Conference. October 16-18. New Orleans.

Pesticides block male hormones

Janet Raloff

From New Orleans, La., at the E.Hormone 2002 meeting

Product labels caution people to handle organophosphate insecticides with respect. Although designed to lethally overstimulate a bug's nerves, these chemicals can attack the human nervous system as well. Now, data suggest that these chemicals may also elicit a more subtle toxicity.

Thomas E. Wiese of Tulane and Xavier Universities in New Orleans wondered whether organophosphate pollutants that structurally resemble androgen-blocking drugs also affect people's hormone activity. So, his team did test-tube studies of a host of these pesticides, including fenitrothion, parathion, chlorothion, linuron, and ruelene.

Hormones work by docking with a specific receptor on a cell, which then responds by turning on genes. Though none of the organophosphates bound to cellular receptors for estrogens, the primary female sex hormones, all attached to androgen receptors. However, they didn't turn on genes, indicating that they don't behave like androgens. That may sound like good news, but because the insecticides to varying degrees block access to those receptors, they can interfere with normal gene activation by preventing a natural androgen, dihydrotestosterone, from docking with its receptor.

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References:

Thomas, S.L., S. Nehls, and T.E. Wiese. 2002. An investigation of the endocrine disrupting potential of organophosphate pesticides. E.Hormone 2002. October 17-19. New Orleans.