The Conversion in Vitro of 17-Hydroxypregnenolone to Cortisol by a Human Adrenal Tumor

Effect of Androgens on Steroid C-21 Hydroxylation*

“…Since in the two-step transformation of pregnenolone to progesterone the isomerase step is faster, the overall rate will be controlled by the latter step. Also, since between -3/3-1 and A5-3-keto the eq" is in favor of 6-3/3-ol, the observation lends support to the Weliky and Engel (1962) hypothesis that 17 -hydroxycorticoids come primarily from 17 -hydroxypregnenolone and not from 17 a-hydroxyprogesterone.…”

“…Recently, several workers (Weliky and Engel, 1962;Berliner et al, 1962;Lipsett and Hokfelt, 1961) have suggested a key role for pregnenolone and 17a-hydroxypregnenolone in the biosynthesis of cortisol. Weliky and Engel (1962) have proposed that the major route to cortisol biosynthesis utilizes 17a-hydroxypregnenolone as substrate.…”

“…Recently, several workers (Weliky and Engel, 1962;Berliner et al, 1962;Lipsett and Hokfelt, 1961) have suggested a key role for pregnenolone and 17a-hydroxypregnenolone in the biosynthesis of cortisol. Weliky and Engel (1962) have proposed that the major route to cortisol biosynthesis utilizes 17a-hydroxypregnenolone as substrate. A strong product inhibition has been observed in the enzymatic transformation of 5pregnen-3,20-dione to progesterone (H. J. Ringold, E. Forchielli, and H. Kruskemper, paper in preparation).…”

Pathways of corticosteroid biosynthesis by homogenates of adrenal tissue from rabbits stimulated with adrenocorticotropin

“…Previous data from our laboratory which compared the efficacy of pregnenolone-4-14C and progesterone-4-14C as precursors for cortisol synthesis by ACTH-stimulated rabbit adrenal tissue (Fevold, 1967) suggested that the Ha-hydroxylase utilized pregnenolone preferentially. Several groups have reported evidence for the existence of a pathway of cortisol biosynthesis involving 17a hydroxylation of pregnenolone in adrenal tissue of human (Lipsett and Hokfelt, 1961;Mulrow and Cohn, 1961;Mulrow etal., 1962;Weliky andEngel, 1962, 1963; Klein and Giroud, 1967; Cameron etal., 1968; Cameron and Griffiths, 1968; Whitehouse and Vinson, 1968), monkey (Lantos et al, 1968), pig (Yudaev and Pankov, 1964), and beef (Ewald et al, 1965) origin. Most of these conclusions have been based on either the relative extent of the conversion of exogenous pregnenolone and progesterone into 17a-hydroxylated products, or on the ability of the tissue to form and/or utilize -hydroxypregnenolone in the formation of cortisol.…”

“…Our data show that a similar pathway exists in ACTH-stimulated rabbit tissue (Figures 1 and 4) and that this is a quantitatively significant pathway in terms of the total amount of cortisol formed under these experimental conditions. In human adrenal tissue (Weliky and Engel, 1963;Klein and Giroud, 1967) there appears to be a relative lack of a 3/3-ol-dehydrogenase AMsomerase enzyme complex to convert pregnenolone into progesterone, based on the observations that little exogenous pregnenolone was converted into progesterone and 17-deoxycorticosteroids, while progesterone was efficiently converted into 17-dexoycorticosteroids and smaller amounts of 17-hydroxycorticosteroids. In ACTHstimulated rabbit tissue, however, there appears to be no de ficiency in the conversion of pregnenolone into progesterone, as the latter is the most rapidly formed initial product of pregnenolone-4-14C metabolism (Figure 2).…”