The subtle and delayed effects of two heavy metals, cadmium and mercury, on the pituitary-adrenal axis of mice were examined. Exeprimental animals were exposed to the toxins both in utero and neonatally via treated mothers' milk. Plasma levels of corticosterone, adrenal production of corticosterone in vitro, and the capacity of the liver to metabolize corticosterone in vitro were studied in these animals as adults. Exposure to methylmercury resulted in diminished hepatic metabolism of corticosterone in vitro due to a loss of liver mass. Adrenal function and plasma levels of corticosterone were unaffected by treatment. Cadmium-exposed animals examined at 277 days of age showed no significant differences when compared to untreated controls. However, when studied at 460-480 days of age, a sex difference in the response to cadmium exposure was noted. In males, the major effect was enhancement of hepatic reductive capacity, while in females, adrenal secretory capacity was enhanced. Possible mechanisms of action and consequences of these effects are discussed.

Adrenal Glands↗

PubMedDate not supplied

Postnatal endocrine dysfunction resulting from prenatal exposure to carbofuran, diazinon or chlordane.

Prenatal exposure to pesticides of three different classes initiated persistent postnatal endocrine dysfunction. Adrenal function and hepatic metabolism of corticosterone were studied in adult hybrid mice exposed during development to either an organophosphate (Diazinon), a carbamate (Carbofuran), or an organochlorine (Chlordane). Animals were exposed to relatively low levels of the toxins in utero and neonatally via the mothers' milk. Exposure to lower doses of the anticholinesterase compounds, Diazinon or Carbofuran, resulted in impairment of hepatic metabolism of corticosterone in vitro due to a loss in reductive capacity per unit liver weight. Plasma levels of corticosterone were also elevated in these animals, but without a concomitant increase in adrenal steroidogenesis in vitro. The effects of exposure to Chlordane were more complex. In male animals, exposure to lower doses of chlordane resulted in an increase in plasma corticosterone levels without an apparent increase in hepatic metabolism of corticosterone or adrenal steroidogenesis. In contrast, side-chain metabolism of corticosterone was decreased in female mice exposed to Chlordane. Similar effects on pituitary-adrenal function were not evident for the offspring of mice exposed to higher doses of the toxins. Possible mechanisms for this non-linear dose-response are discussed.

Adrenal Glands↗