Other conceivable renditions of some of the oxidative processes used in the biosynthesis of steroid hormones

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 101; no. 1; pp. 31 - 41
• Main Authors: Lieberman, Seymour, Kaushik, Gayathri
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2006
• Subjects: Cytochrome P-450 Enzyme System - metabolism; Free radical “reactive intermediates”; Hormones - biosynthesis; Oxidation-Reduction; Oxidative processes; Steroidogenesis; Steroids - biosynthesis; Substrate Specificity; Free radical “reactive intermediates”; Oxidative processes; Steroidogenesis
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2006.06.005

The generally accepted version (GAV) of the chemical processes by which the steroid hormones are biosynthesized cannot be considered to be an inerrant description of in vivo processes. Customarily this version is derived by piecing together the results obtained from several independent artificial in vitro incubation experiments. Extrapolation of such results from in vitro to in vivo requires untested assumptions which introduce varying degrees of uncertainty. In vitro incubation experiments reveal only what is possible; not what actually prevails in situ. Presented here are hypothetical alternative renditions of some of the oxidative processes involved in steroidogenesis. These versions suggest that some cytochrome P-450's catalyze the introduction of both oxygen atoms of dioxygen into an appropriate sterol precursor. The products are conceived as oxygen free radicals (peroxy or 1,2-cyclic peroxy) which serve as the “reactive intermediates” (the precursors) for the hormones. The true intermediates are not stable, isolable, hydroxylated compounds as they are customarily portrayed in the GAV. Central to these new renditions is the hypothesis that the appropriate P-450 introduces dioxygen into the precursor yielding either: A, a 20 peroxy sterol species or B, a species oxygenated at both C-17 and C-20 or C, a species oxygenated at both C-20 and C-21. In this hypothesis, A would serve as the precursor for progesterone, B, for the C 19-androgens and C 18-estrogens and C, for the mineralocorticoids (corticosterone and aldosterone) and the glucocorticoid (cortisol). How this version of steroidogenesis can be used to understand the etiologies of various genetically derived enzyme deficiency diseases of the adrenal and ovaries will be discussed. If as proposed here, the various polyfunctional cytochromes (P-450 scc, P-450 c17, P-45011B1 (P-450 cortisol), P-45011B2 (P-450 aldo), etc.) catalyze conversions that are different from simple hydroxylations, the labels usually given these deficiency diseases may not be appropriate. More importantly, these new conceptions may clarify the etiology of some of the characteristic symptoms of these diseases that are not now adequately explained by the GAV.