Michael Waterman
Faculty Member
Last active: 2/12/2015

Incorporation of steroidogenic pathways which produce cortisol and aldosterone from cholesterol into nonsteroidogenic cells.

Mathew PA, Mason JI, Trant JM, Waterman MR
Mol Cell Endocrinol. 1990 73 (1): 73-80

PMID: 2292341

Cortisol production from cholesterol requires the activity of four steroid hydroxylases: cholesterol side chain cleavage cytochrome P-450 (P-450scc), 17 alpha-hydroxylase cytochrome P-450 (P-45017 alpha), 21-hydroxylase cytochrome P-450 (P-450C21) and 11 beta-hydroxylase cytochrome P-450 (P-45011 beta). We have previously shown that transformed, nonsteroidogenic COS 1 cells derived from monkey kidney are a useful system for expression of various forms of cytochrome P-450. The present study shows that COS 1 cell cultures multiply transfected with six plasmids containing all four steroid hydroxylases, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta HSD) and adrenodoxin produce cortisol and aldosterone when 22(R)-hydroxycholesterol is supplied to the system. When pregnenolone is used as substrate, various intermediate metabolites are detected at different time points further establishing the incorporation of complete functional steroidogenic pathways into the nonsteroidogenic cell cultures. Since the first and the last reactions in these pathways take place in the mitochondrion, the movement of various intermediate metabolites from mitochondrion to endoplasmic reticulum and back to mitochondrion occurs in and between COS 1 cells.

MeSH Terms (13)

Adrenodoxin Aldosterone Animals Cells, Cultured Cercopithecus aethiops Cholesterol Hydrocortisone Kidney Organ Specificity Recombinant Fusion Proteins Steroid Hydroxylases Substrate Specificity Transfection

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