Pituitary and adrenal responses to pulsatile ovine corticotropin-releasing factor administered to fetal sheep.

In fetal sheep a bolus injection of ovine CRF (oCRF) elevates plasma immunoreactive ACTH (IR-ACTH) during the last 5 weeks of gestation. However, the effects of long term administration of oCRF to fetal sheep have not been studied. We examined the effects of pulsatile administration of oCRF (1 microgram every 4 h) for 7 days on fetal pituitary and adrenal responses, as reflected by plasma concentrations of IR-ACTH and cortisol (F). In addition, we examined the effects of oCRF on cAMP accumulation by dispersed pituitary cells in vitro after treatment in vivo with either oCRF or saline. Pulsed oCRF (P-CRF) treatment resulted in a significant (P less than 0.05) increase in basal IR-ACTH and F concentrations on all days of treatment. However, the pituitary response (change in IR-ACTH in response to a pulse of oCRF) decreased, and the adrenal response (change in F in response to endogenously secreted ACTH) increased as treatment progressed. A significant inverse correlation (r = 0.962) between basal F and the IR-ACTH response to oCRF was seen over the 7 days of treatment. Although P-CRF treatment resulted in an increase in fetal adrenal weight, it did not lead to premature parturition. There was a dose-dependent accumulation of cAMP in response to oCRF in vitro by dispersed pituitary cells from both groups of fetuses. However, this response was significantly greater when the fetuses had been pretreated with oCRF in vivo than after saline treatment. We conclude that the P-CRF regimen employed in this study stimulates the fetal pituitary-adrenal axis and the ability of fetal pituitary cells to accumulate cAMP in response to further oCRF in vitro. The reduced plasma IR-ACTH response after continued P-CRF in vivo may be attributed to increasing negative feedback effects of elevated endogenous F.