The hypothalamic-pituitary-adrenocortical axis plays an essential role in the maturation of fetal organs and, in sheep, birth. Lesioning the paraventricular nucleus (PVN) in fetal sheep prevents adrenocortical maturation and parturition without altering plasma immunoreactive ACTH concentrations. The purpose of this study was to determine the effect of PVN-lesion on anterior pituitary processing of POMC to ACTH, plasma concentrations of ACTH and ACTH precursors (POMC; 22 kDa proACTH) and expression of subtilisin-like prohormone convertase 3 (SPC3) in corticotropes in fetal sheep. PVN lesion did not affect anterior pituitary POMC and 22 kDa proACTH levels while ACTH was significantly The ACTH-precursor (POMC plus 22 kDa proACTH) to ACTH ratio in the anterior pituitary was significantly increased following PVN-lesion. Post-PVN lesion, fetal plasma ACTH_1-39 was below the limit of detection while ACTH precursors (POMC plus 22 kDa proACTH) were not affected. In the inferior region of the anterior pituitary, 40-50% of corticotropes had detectable SPC3 hybridization signal and PVN-lesion did not change the extent of co-localization of POMC and SPC3, or SPC3 mRNA levels within corticotropes. Neither the percent of corticotropes in the superior region containing SPC3 hybridization (7-12%) or hybridization signal strength was altered response to PVN-lesion. In conclusion, the fetal PVN is necessary for sustaining adequate anterior pituitary processing of POMC to ACTH and ACTH release needed for maturing the adrenal cortex in the sheep fetus.