Adrenocorticotropin (ACTH) and corticosterone secretion by perifused pituitary and adrenal glands from rodents exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Although in utero maternal stress has been shown to have lasting effects on rodent offspring, fetal effects of chemically-induced alterations of the m aternal hypothalamic-pituitary-adrenal axis (HPA) have not been well studie d. This study examined the effects of in vivo 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) exposure on pituitary-adrenal function in the male rat, pregn ant female rat and pregnant female mouse. The secretion of adrenocorticotro pin (ACTH) and corticosterone (CORT) in pituitary and adrenal glands, respe ctively, was assessed in ex vivo perifusion cultures. Mali and pregnant fem ale (gestation day 8) Sprague-Dawley rats were gavaged once with 10 mug/kg TCDD, pregnant female mice once with 24 mug/kg TCDD, and euthanized 10 days later. Hemi-pituitary (rat) or whole anterior pituitaries (mice) and right adrenal glands from the same animal were quartered. perifused under baseli ne and stimulated conditions. In both males and pregnant females, TCDD did not affect corticotropin releasing hormone (CRH)-stimulated ACTH secretion. Neither total pituitary ACTH nor plasma ACTH was altered in either sex or species by TCDD treatment. ACTH-stimulated CORT secretion was not affected by TCDD in either sex or species, and adrenal tissue and plasma CORT levels were unchanged in males and pregnant females by TCDD. However, the plasma ACTH:CORT ratio was decreased about 46% in male rats treated with TCDD. Pla sma CORT levels were 23-fold higher and plasma ACTH levels were 1.5-fold hi gher in pregnant females than in male rats. In male versus female rats, adr enal CORT and anterior pituitary ACTH tissue levels were about 7.5- and 1.7 5-fold higher and ACTH, respectively. Female mouse adrenal tissue CORT was about 4-fold greater than female rat. The reduced plasma ACTH:CORT ratio in the male rat suggests that TCDD disturbs HPA function. Exposure of male ra t to a 5-fold higher dose in earlier studies clearly demonstrated effects o f TCDD on male rat HPA. The present study identified substantial HPA perfor mance differences between male and pregnant female rats. The failure to det ect a response to TCDD in pregnant female rat and mouse could be a function of both TCDD dose and the high level of secretion of both ACTH and CORT in pregnant animals. For the rat or mouse, a single exposure to TCDD during p regnancy does not appear sufficient to induce maternally-mediated developme ntal. reproductive and behavioral toxicity via the HPA axis. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.