Effect of placement of dexamethasone adjacent to the ovine fetal paraventricular nucleus on adrenocortical steroid hydroxylase messenger ribonucleic acid.

Abstract

The preterm rise in the concentration of ovine fetal plasma cortisol that initiates the events of parturition in sheep commences at approximately 125 days of gestational age (dGA; term = approximately 147 dGA). Concurrent with the rise in fetal plasma cortisol, adrenocortical steroid hydroxylase enzyme activity increases. The purpose of this study was 1) to quantitate changes in levels of mRNA for the steroid hydroxylases, 17-hydroxylase cytochrome P450 (P450(17)alpha), side-chain cleavage cytochrome P450 (P450scc), 11 beta-hydroxylase cytochrome P450 (P450(11)beta), and C21-hydroxylase cytochrome P450 (P450C21); and 2) examine the role of the fetal paraventricular nucleus (PVN) in the onset of adrenocortical steroid hydroxylase mRNA expression. Unperturbed fetuses were collected by cesarian section under halothane anesthesia at 105 (n = 4), 120 (n = 4), 126-128 (n = 4), and 136 dGA (n = 3); neonatal animals were collected within 2 h after birth. To examine the role of the fetal PVN in regulation of adrenocortical steroid hydroxylase mRNA expression, ovine fetuses were stereotaxically implanted bilaterally 2 mm lateral to the fetal PVN at 105-107 dGA with either cholesterol (n = 4) or dexamethasone (DEX; n = 3). Implanted fetuses were collected by cesarian section under halothane anesthesia at 126-128 dGA. mRNA for both cytochrome P450(17)alpha and P450scc declined 3-fold from 105 to 120 dGA (P less than or equal to 0.05), and then increased by 126-128 dGA compared to that on 120 dGA (P less than or equal to 0.05) and continued to increase through term. Cytochrome P450C21 increased at 126-128 dGA compared to that on 105 and 120 dGA (P less than or equal to 0.05) and remained elevated through term. Three distinct transcripts [approximately 6.2, 4.2, and 2.5 kilobases (kb)] were observed for cytochrome P450(11)beta; the 4.2-kb transcript was predominant. While total message for P450(11)beta declined over increasing gestational age, no differences were noted for the 4.2-kb transcript until after birth, when levels significantly declined (P less than or equal to 0.025). Placement of DEX adjacent to the fetal PVN prevented reemergence of expression of mRNA for P450(17)alpha and P450scc at 126-128 dGA, but had no effect on mRNA for P450C21 or P45011 beta. We conclude that mRNA for P450(17)alpha and P450scc undergoes a decline in expression concurrent with the previously described period of adrenal hyporesponsiveness from 105-126 dGA, followed by an increase in mRNA that accompanies the preterm rise in fetal plasma cortisol.(ABSTRACT TRUNCATED AT 400 WORDS)