Therefore, in Vil-Cre-HSD2(-/-) Apc(min/+) mice, epithelial cell 11β-HSD2 deficiency leads to inhibition of adenoma initiation and growth by attenuation of COX-2 expression, increased cell-cycle arrest, and inhibition of mTOR signaling as a result of increased tumor intracellular active glucocorticoids.
HSD11B2 mRNA levels were high in nonfunctioning adenomas and preclinical Cushing's adenomas compared with levels in control adrenals or in adenomas causing overt Cushing's syndrome.
Nonfunctioning adenomas and those causing preclinical and overt Cushing's syndrome may represent a continuum with clinical manifestations depending mainly on tumor size and HSD11B2 expression levels.