Inhibition of CYP17 expression by adrenal androgenes and transforming growth factor-beta in adrenocortical cells

• Autorzy: Biernacka-Lukanty J. M. , Lehmann T.P. , Trzeciak W.H.
• Języki publikacji: EN

Abstrakty

EN

Cytochrome P450c17, encoded by the CYP17 gene, is a component of the 17a-hy- droxylase/17,20-lyase enzyme complex essential for production of adrenal gluco­corticoids and androgens as well as gonadal androgens. The expression of CYP17 in adrenocortical cells is stimulated by corticotropin (ACTH) via the signal trans­duction pathway involving cAMP and protein kinase A (PKA). Thus, in addition to glucocorticoids, ACTH stimulates formation of adrenal androgens, which are known to induce transforming growth factor 3 (TGF-3) secretion. TGF-3 in turn inhibits ste­roid hormone output by attenuating both basal and ACTH-dependent expression of CYP17. The present study revealed that treatment of bovine and human H295R adrenocortical cells with androgens resulted in a decrease in the basal level of CYP17 transcript and cortisol secretion, without affecting forskolin-stimulated lev­els. We also demonstrated that in H295R cells TGF-3 inhibited both basal and forskolin-stimulated accumulation of CYP17 mRNA. Determination of promoter ac­tivity, directing luciferase reporter gene expression in H295R cells transfected with deletion fragments of bovine CYP17 promoter, indicated that the -483 to -433 bp fragment of the promoter was necessary for the inhibitory action of TGF-3 on CYP17 expression. It is concluded that in bovine and human adrenocortical cells, androgens inhibit basal CYP17 expression probably at the transcriptional level and independently of the effect of TGF-3.

Słowa kluczowe

EN

adrenocortical cell; transforming growth factor-beta; gene expression; CYP17 gene; cytochrome P450

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2004
• Tom: 51
• Numer: 4
• Opis fizyczny: p.907-917,fig.,ref.

Twórcy

autor

Biernacka-Lukanty J. M.

• University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland

autor

Lehmann T.P.

autor

Trzeciak W.H.

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