The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

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   Figure 1

   The structures of deoxycorticosterone (DOC), deoxycorticosterone acetate (DOCA), corticosterone and aldosterone (in two forms, see Brookes et al. (2011)). According to a prevailing view, corticosterone is primarily a glucocorticoid, aldosterone primarily a mineralocorticoid, and DOC is a weak mineralocorticoid with no glucocorticoid activity. Since corticosterone differs from DOC only by the presence of an 11β-hydroxyl group, but aldosterone has a more complex acetal or hemiacetal structure, these functional designations defy rational interpretation of steroid structure–function relationships.
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   Figure 2

   Data extracted from the papers of Ingle (1940a,b) (his Figs 1 (unoperated controls) and 3 (adrenalectomised animals)), and Vögtli (1943a,b) (his Table 1) and replotted. Adrenalectomised rats were treated for 7 days with 2 mg DOC (Ingle), or after 4–6 days with 1 mg DOCA (Vögtli), and then tested in the loaded gastrocnemius muscle contraction assay. The preparations were stimulated three times per second for 12 h (intact and adrenalectomised controls) or until the preparation failed (adrenalectomised and steroid treated) (Ingle), or for 8 h (Vögtli). The original data points were listed in a table (Vögtli) or individually plotted, with a mean value shown (Ingle). This figure shows mean±s.d. (n, numbers in columns), calculated by the present author. In each data set, adrenalectomised values are significantly lower than either unoperated or adrenalectomised and treated, P<0.00001. For clarity, limited data sets are shown here, both Ingle & Vögtli gave more, including comparison with cortisone or cortisone acetate (Ingle) or the adrenal extract cortin (Vögtli). Ingle also showed clear dose dependency of the DOC and DOCA effect. In his experiments, only cortisone acetate at 2 mg gave values higher than those obtained with DOC. The y-axis units are of the original authors. There is an error in Ingle's y-axis, and the highest values here are, in reality, effectively up to 20 000 revolutions of his recorder, not 0.02 revolutions as the axis label suggests, which would give rise to an unfeasibly (and unmeasurably) low value for work performed. Ingle equates 1 revolution to 400 gcm work. This would give maximum values of about 60 mkg in Vögtli's units. While this is at least five- to six-fold greater than Vögtli achieved (note Vögtli's values are per 100 g BW: both authors used animals of about 150 g BW), it at least is of the same order of magnitude as Vögtli's and the differences could perhaps be accounted for by differences in the equipment/technique, or the longer sampling periods used by Ingle. In any case, the strikingly similar data in the two figures here strongly indicate that the two authors measured the same thing. Vögtli interpreted his data to support the view that DOCA could completely restore the work capacity of the gastrocnemius muscle of the adrenalectomised rat. His conclusions were vehemently opposed by Ingle (1945) (see text).
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   Figure 3

   Neuroactive steroids. THDOC and 3α,5β-tetrahydro-DOC are derived from DOC in the brain, where they exert anxiolytic and other actions. The progesterone derivatives have similar actions.

• © 2011 Society for Endocrinology