Effect of transforming growth factor beta-1 on the cholesterol side-chain cleavage system in the adrenal gland of sheep fetuses and newborns.
The present work examined the effect of transforming growth factor-beta1 (TGFbeta1) on the cholesterol side-chain cleavage system of sheep fetal and neonatal adrenal glands. Freshly isolated fetal adrenal cells produced 3-fold less pregnenolone from 22R- hydroxycholesterol than neonatal cells. Also, the relative amounts of immunoreactive cytochrome P450 side-chain cleavage (P450scc), adrenodoxin, and adrenodoxin reductase were 1.5- to 2-fold lower in mitochondria from fetal than neonatal cells. However, during culture under control conditions, the cholesterol side-chain cleavage activity and the amounts of P450scc, adrenodoxin, and adrenodoxin reductase of fetal cells increased after 48 h to reach neonatal values. A 5-day treatment with TGFbeta1 (1ng/ml) decreased significantly both the cholesterol side-chain cleavage activity and the amounts of immunoreactive P450scc, adrenodoxin, and adrenodoxin reductase in sheep fetal and neonatal adrenal cells in culture. Immunoreactive TGFbeta1- like material was present in freshly isolated adrenal cells from both fetuses and newborn lambs. After 2 days of culture, the amount of TGFbeta1-like protein was 2-fold lower than in freshly isolated fetal cells. No change was observed for neonatal cells. Finally, TGFbeta1 encoding messenger RNAs and TGFbeta-like immunoreactive protein were much higher in adrenal cortices from fetuses than from neonates. Taken together, these results have made TGFbeta1 a potentially attractive candidate for being an auto/paracrine negative regulator of the cholesterol side-chain cleavage system in the sheep fetal adrenal gland.
Naaman-Reperant
E
E
INRA, Nouzilly, France.
Hales
D B
DB
Durand
P
P
D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D000325:Adrenodoxin / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D000325:Adrenodoxin; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D005287:Ferredoxin-NADP Reductase