PRENATAL DEXAMETHASONE OR STRESS BUT NOT ACTH OR CORTICOSTERONE ALTERSEXUAL-BEHAVIOR IN MALE-RATS

Prenatal maternal stress in rats and mice can demasculinize and femini ze the sexual behavior of adult male offspring. Causal mechanisms are unknown, but one attractive hypothesis is that stress activation of ma ternal adrenal glucocorticoid secretion is the responsible agent. To t est this hypothesis, pregnant rats were exposed to a variety of substa nces which enhance glucocorticoid actions. These included ACTH (20 IU of a gel preparation, SC once daily), corticosterone (CORT; 7 mg/kg SC in oil, three times daily), or dexamethasone (DEX; 0.1 mg/kg, SC once daily). Controls included noninjected dams and a positive stress cont rol group (restraint under bright lights three times daily). All treat ments reduced maternal weight gain, DEX most potently. No treatment al tered litter size, stillbirths, or sex ratio, but DEX reduced weight a t birth, an effect still seen at postnatal day 85. DEX, CORT, and stre ss reduced male adrenal weight at birth, while DEX and CORT altered se xual differentiation as measured by anogenital distance. Stress impair ed adult male sexual performance but not the lordosis quotient followi ng exposure of animals to stud males. DEX affected both measures. No o ther treatment had any significant effect on sexual behavior. No treat ment altered plasma LH levels, either basal or in response to an estro gen challenge in adult gonadectomized males. In adulthood there was no treatment effect on stress reactivity, measured behaviorally or by pl asma glucocorticoids. Correlational analysis revealed that weight gain during pregnancy was the single best predictor of subsequent sexual p erformance. It is concluded that prenatal dexamethasone exposure demas culinizes and feminizes male offspring. Whether the similar effect of stress is mediated solely by adrenal glucocorticoids is less certain; the ACTH and CORT treatments produced maternal plasma corticosterone l evels higher than in stressed dams, yet did not affect adult sexual be havior. Because at high doses many drugs elicit a maternal stress resp onse, including glucocorticoid secretion, these findings suggest that there may be a common effect of prenatal drug exposure upon sexual dif ferentiation in the rat.