Effect of bilateral lesions of the ovine fetal hypothalamic paraventricular nuclei at 118-122 days of gestation on subsequent adrenocortical steroidogenic enzyme gene expression

Fetal adrenal steroid hydroxylase activity and messenger RNA (mRNA) expression increases concurrent with the preterm rise in fetal plasma cortisol during late gestation in sheep. By placing bilateral lesions of the fetal paraventricular nuclei (PVN) we have previously demonstrated that the fetal PVN is necessary for the initiation of parturition, the late gestation preparturient increase in fetal plasma cortisol and ACTH, and ACTH secretion in response to fetal hypoxemia and hypotension. The purpose of this study was to determine the role of the fetal PVN in the late gestation increase in expression of mRNA for 17α-hydroxylase (P-450_17α), side-chain cleavage (P-450_SCC), 11β-hydroxylase (P-450_11β), 21 hydroxylase (P-450_C21), and 3β-hydroxy- steroid dehydrogenase (3β-HSD) in the fetal adrenal. Ovine fetuses were subjected to bilateral lesions of the PVN (Lx; n = 4) or sham lesions (Sh; n = 4) at 118-122 days gestational age (dGA). Lx fetuses were recovered by cesarean section at greater than or equal to 157 dGA; Sh fetuses were recovered immediately postbirth at normal term (146.5 ± 0.9 dGA). In addition, uninstrumented fetuses were obtained at 145-147 dGA by cesarean section (n = 3). RNA obtained from individual fetal adrenals was subjected to Northern analysis. Lx of the fetal PVN decreased (P < 0.05) mRNA for P-450_17α and P-450Scc but did not affect adrenocortical mRNA for P-450_C21, P-45011(S, or 3β-HSD com-pared to Sh. To determine if the differences observed between Lx and Sh for P-450_17α and P-450Scc mRNA were due to the process of labor, we compared uninstrumented 145-147 dGA to Sh. No differences in adrenal mRNA content were observed for P-450_17α or P-450snn between these groups. We conclude that in late gestation fetal sheep an intact fetal PVN is necessary for normal gene expression of adrenocortical P- 450_17α and P-450Scc while P-450_11β, P-450_C21, and 3β-HSD may be primarily regulated by factors not dependent upon a functional PVN.