Effects of transforming growth factor-beta 1 on human adrenocortical fasciculata-reticularis cell differentiated functions.
Transforming growth factor-beta 1 (TGF beta 1) has been reported to have a strong inhibitory effect on the specific function of adrenal cells of several species. In the present study, we examined the effects of TGF beta 1 on cultured human fasciculata-reticularis cells. TGF beta 1 alone had no effect on ACTH receptor messenger ribonucleic acid (mRNA) levels and was unable to reduce the strong stimulatory effects of ACTH on its own receptor. However, TGF beta 1 enhanced angiotensin-II type 1 receptor mRNA and binding sites. Treatment with TGF beta 1 increased significantly the levels of 3 beta-hydroxysteroid dehydrogenase mRNA, reduced those of cytochrome P-450 17 alpha-hydroxylase mRNA, and had no effect on cholesterol side-chain cleavage cytochrome P-450 mRNA. Whatever the experimental condition, TGF beta 1 did not reduce basal or ACTH-stimulated cortisol production, but the production of dehydroepiandrosterone sulfate of TGF beta 1-treated cells was always decreased. The effects of TGF beta 1 on 3 beta-hydroxysteroid dehydrogenase mRNA and dehydroepiandrosterone sulfate were opposite the change observed at the time of adrenarche. As adrenal cells express TGF beta 1 mRNA, it is tempting to postulate that a local diminution of TGF beta 1 might be involved in adrenarche. Our findings also illustrate the specific species differences and, therefore, the caution to extrapolate to humans the results observed in other species.
INSERM-INRA U-307, Hôpital Debrousse, Lyon, France.
M C
MC
Lebrethon
C
C
Jaillard
D
D
Naville
M
M
Bégeot
J M
JM
Saez
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate; D004798:Enzymes / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*
D004798:Enzymes; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D018125:Receptors, Transforming Growth Factor beta; D013256:Steroids; D016212:Transforming Growth Factor beta; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone