
TY  - JOUR
A1  - Coulter, C. L. 
T1  - 043. Role of TGF&#946; in adrenal steroidogenesis before birth
JF  - Reproduction, Fertility and Development
JO  - Reprod. Fertil. Dev.
Y1  - 2004
VL  - 16
IS  - 9
SP  - 43
EP  - 43
KW  - 
UR  - https://doi.org/10.1071/SRB04ABS043 
N2  - 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. A range of studies in the rat and sheep have also demonstrated that exposure to excess glucocorticoids at inappropriate times in fetal life inhibits fetal growth and permanently reprograms the development of the cardiovascular and metabolic systems resulting in postnatal hypertension, abnormal hepatic glucose production and poor glucose tolerance In most mammalian species, there are therefore a range of mechanisms that protect the fetus from exposure to glucocorticoids of either maternal or fetal origin at inappropriate times in gestation. The factors that act to maintain periods of adrenal quiescence are not known. There is evidence that intra-adrenal transforming growth factor beta 1 (TGF&#946;1) is an inhibitor of adrenocortical steroidogenesis in the adult. In recent studies, we have demonstrated that expression of TGF&#946;1 is high in the fetal sheep adrenal at around 100 days gestation and that adrenal TGF&#946;1 expression then falls with increasing gestational age and is lowest immediately after birth. Following the activation of adrenal cytochrome P450 C17 (CYP17), there is an inverse relationship between adrenal TGF&#946;1 and CYP17 expression and TGF&#946;1 may therefore play a novel inhibitory role in the regulation of adrenal steroidogenesis during mid and late gestation. Whilst functional activation of the fetal adrenal is dependent on the fetal hypothalamo&#8211;pituitary axis, adrenal TGF&#946;1 mRNA expression is not altered by disconnection of the fetal hypothalamus and pituitary in late gestation. It therefore appears unlikely that TGF&#946;1 mRNA expression is regulated directly by either bioactive ACTH or cortisol in late gestation. The mechanism by which TGF&#946;1 expression is upregulated in mid gestation remains to be determined. 
ER  -

