A Heuristic Proposal for Understanding Steroidogenic Processes

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Abstract
Introduction The generally accepted pathways of steroidogenesis are customarily presented by a scheme such as that shown in Fig. 1. This two-dimensional picture can be conveniently reproduced on a printed page and is easily memorized. It provides, however, too simplistic a view which can lead to serious misconceptions. By depicting the biochemical transformations it concentrates on the apparent common features of the various pathways but ignores many important differences. The scheme indicates that one sterol, cholesterol, serves as a precursor for all the hormones. The possibility that other derivatives of cholesterol may also be progenitors of important steroidal products is not taken into account. Cholesterol esters, particularly cholesterol sulfate, are examples of such precursors. For more than 15 years (1) it has been known that the abundant adrenal secretory product, dehydroisoandrosterone sulfate, can be biosynthesized from cholesterol sulfate through pathways that involve sulfated intermediates which, it may be noted, do not appear in the scheme shown in Fig. 1. The scheme further assumes that the intermediates in the various processes are stable, isolatable compounds (such as pregnenolone, 17-hydroxypregnenolone,1etc.). However, decade-old evidence suggests that in at least some, if not all, processes the true intermediates are probably complexed with some components of the enzyme systems catalyzing the processes (2) and therefore the isolation of a stable entity from excreta or as a product of an in vitro experiment does not constitute proof of its intermediacy.

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