Adrenal TGFbeta1 mRNA levels fall during late gestation and are not regulated by cortisol in the sheep fetus

During mammalian development there are periods when the fetal adrenal is either relatively refractory or increasingly sensitive to trophic stimulation. This pattern of regulation of adrenal growth and function ensures that the fetal lungs, liver, brain and kidney are exposed in a programmed temporal sequence to the genomic actions of circulating glucocorticoids. The factors which act to maintain periods of adrenal quiescence are not known. In the present study we have measured the level of messenger RNA (mRNA) expression of a putative inhibitor of adrenal steroidogenesis, transforming growth factor beta 1 (TGFbeta1), and a key steroidogenic enzyme, cytochrome P450 17alpha hydroxylase (CYP17), during periods of adrenal quiescence and activation in the sheep fetus. We have also investigated the relative roles of the fetal hypothalamic-pituitary axis and cortisol in the regulation of expression of adrenal TGFbeta1 and CYP17 mRNA during late gestation. Adrenal expression of TGFbeta1 was greatest at around 100 days gestation, at a time when the fetal sheep adrenal is relatively refractory to trophic stimulation and there was an inverse relationship between the expression of TGFbeta1 and CYP17 mRNA in the adrenal gland during the peripartum period. Whilst disconnection of the fetal hypothalamic-pituitary disconnection (HPD) axis resulted in a decrease in adrenal CYP 17 mRNA expression, there was no effect of fetal HPD, with or without cortisol replacement, on adrenal TGFbeta1 mRNA expression in late gestation. Thus TGFbeta1 may play a role in inhibiting adrenal steroidogenesis and ensuring that the adrenal remains relatively refractory to trophic stimulation during mid gestation. The maintenance of low adrenal TGFbeta1 expression during late gestation is not dependent, however, on stimulation by the fetal hypothalamic-pituitary axis.Catherine L. Coulter, Mark D. Salkeld, I. Caroline McMille