Transformation Of Pregnenolone Research Articles

Biotransformation XLVII: transformations of 5-ene steroids in Fusarium culmorum culture

The course of the transformation of six 5-ene steroids with varying substituents at C-17 or/and C-3: dehydroepiandrosterone (DHEA), 5-androsten-3β,17β-diol, 17α-methyl-5-androsten-3β,17β-diol, 5-androsten-17-one, 5-androsten-3β-ol and pregnenolone by Fusarium culmorum was investigated. Three substrates with oxygen functions at C-3 and C-17 i.e. DHEA, 5-androsten-3β,17β-diol and 17α-methyl-5-androsten-3β,17β-diol were hydroxylated entirely at 7α-axial, allylic position. The mixture of 7α-hydroxy- and 7α,15α-dihydroxyderivatives was formed during the transformation of pregnenolone and 5-androsten-17-one, from the latter 2α,7α-dihydroxyderivative was also obtained. 7α,15α- Dihydroxyderivative was the only product isolated from the 5-androsten-3β-ol post-transformation mixture. The time-course of the DHEA transformation by F. culmorum shows that the substrate induces 7α-hydroxylase activity. DHEA was transformed by androstenedione induced F. culmorum cultures to a larger extent than by a noninduced microorganism; the selectivity of the transformation remained unchanged.

A delta 4-3-keto pathway for testosterone synthesis in the human spermatozoa.

The ability of human spermatozoa to metabolize pregnenolone to progesterone and progesterone to testosterone was assessed. Sonicated specimens of freshly ejaculated sperm from two groups of husbands (n = 6, age 32-38 years; n = 6, age 30-51 years) of infertile couples in the range of sperm concentration between 237.5 and 568.5, 100.1 and 248.8 millions per ejaculate, were separately incubated with [7n-3H]pregnenolone and [1,2,6,7,16,17-3H]progesterone. Using the classical reverse-isotope dilution technique the desired products [3H]progesterone and [3H]testosterone formed from the respective substrates were isolated and characterized, yielding 1.4 to 12.2% and 3.1 x 10(-2) to 2.0 x 10(-1)%. Such metabolites were not evident in the controls. The results indicate that the human spermatozoa contain the enzymes necessary for the transformation of pregnenolone to testosterone via the delta 4-3-keto route.

Characterization of a delta 5-3 beta-hydroxy pathway of testosterone synthesis in the human spermatozoa.

Sonicated specimens of freshly ejaculated sperm from two groups of husbands (n = 6, age 32-38 years; n = 7, age 27-38 years) of infertile couples in the range of sperm concentration between 237.5 and 568.5; 131.1 and 256.7 millions per ejaculate were separately incubated with [7n-3H]pregnenolone and [1,2,6,7(-3)H]dehydroepiandrosterone. Using the reverse-isotope dilution technique [3H]dehydroepiandrosterone and [3H]testosterone formed from the respective substrates were isolated and characterized, yielding 1.2 x 10(-2) to 4.6 x 10(-20/0) and 7.1 x 10(-2) to 2.5 x 10(-10/0)/ Such metabolites were not evident in the controls. These results provide evidence for metabolic transformation of pregnenolone to testosterone via the delta 5-3 beta-hydroxy route.

?5-3?-hydroxysteroid dehydrogenase/?5-?4-ketosteroid isomerase (3?-HSD), a possible enzyme of cardiac glycoside biosynthesis, in cell cultures and plants of Digitalis lanata EHRH

The in vitro transformation of pregnenolone into progesterone in Digitalis lanata tissues was shown to be catalyzed by a 3β-hydroxysteroid dehydrogenase/ketosteroid isomerase (3β-HSD). Product formation was monitored by HPLC. The enzyme could be partially characterized and 3β-HSD activities were measured in various Digitalis lanata tissues and in cell cultures of other plant species. Since no correlation was observed between biosynthetic competence of the tissue and 3β-HSD activity, it was concluded that this enzyme does not play a major role in regulating cardenolide biosynthesis.

Rat placental delta-5-3 beta-hydroxysteroid dehydrogenase. I. Changes in activity with dilution and gestational age.

The 10,000 × g supernatant from homogenates of rat placenta of 13 to 20 days gestational age converted 4-14C-pregnenolone to progesterone in the presence of NAD. The yield of progesterone per g of tissue decreased as gestational age advanced. Dilution of the preparation resulted in increased specific activity. A plot of the reciprocal of the specific activity against the protein concentration gave a straight line, and the slope of this line increased with increasing gestational age. Progesterone was the only product found when NAD was the sole cofactor, but the use of ATP plus NADPH resulted in high yield of polar, probably reduced, products. The potential for progesterone synthesis of rat placentas was shown to be greater than was previously believed. The hypertrophied placentas from a rat with a uterine infection showed an increase rate of transformation of pregnenolone to progesterone. Pregn-4-ene-20〝-ol-3-one was a noncompetitive in vitro inhibitor of progesterone synthesis. It may be involved in cont...

Transformation of pregnenolone and progesterone by cultured plant cells.

THE amounts of secondary metabolites accumulated by in vitro cultures of plant cells have generally been disappointingly small and attempts to transform exogenous substrates by cultures of plant cells have not hitherto been much more successful1.

Biogenesis of corticosteroids in the European eel Anguilla anguilla L.

SUMMARY Incubation, with [4-14C]progesterone, of adrenocortical tissue (posterior cardinal vein preparations) from the eel yielded 14C-labelled cortisol and cortisone. These two hormones, containing both 14C and 3H, appeared when similar preparations were incubated simultaneously with [4-14C]progesterone and [16-3H]pregnenolone. In addition, the following intermediaries were isolated: [14C, 3H]progesterone; [14C, 3H]17α-hydroxyprogesterone; [3H]17α-hydroxypregnenolone and [14C, 3H]21-deoxycortisol. Analysis of the isotope content of the end products and isolated intermediaries seemed to indicate that the transformation of pregnenolone to corticosteroids proceeded to a large extent through intermediaries other than progesterone. In none of these experiments could the formation of aldosterone be demonstrated. Similarly, incubation of eel adrenocortical tissue with a mixture of [4-14C]-progesterone and [1,2-3H]corticosterone failed to yield detectable aldosterone. A further search for aldosterone, using a large amount of eel adrenocortical tissue with [4-14C]progesterone and [16-3H]pregnenolone as substrates with added angiotensin, also gave negative results. In similar preparations, [1-14C]sodium acetate was not transformed to any recognizable corticosteroids.

Evidence for in Vivo Conversion of C21 Steroids to C19 Androgens in the Bovine

Summary The biosynthetic transformation of progesterone to fecal androgen (androstenedione) in the bovine has been shown. The present study reports the biosynthetic transformation of pregnenolone and 17 α -hydroxyprogesterone to fecal androgen. Following the injection of pregnenolone into the male and female bovine, the chick comb response test demonstrated a significant formation of fecal androgens in the male and a significant increase in fecal androgens in the female. Following the injection of 17 α -hydroxyprogesterone into the female bovine, androgen biosynthesis was evidenced by the excretion of a significant amount of fecal androgens as measured by the chick comb response test. In vitro studies with various mammalian tissues have documented a pathway for androgen biosynthesis involving the following sequence: pregnenolone → progesterone → 17 α -hydroxyprogesterone → androstenedione. The cumulative results of the experiments on bovine androgenesis provide in vivo evidence indicating that androgen biosynthesis in the bovine, as in many other species, occurs via the same pathway. The experimental evidence demonstrates further the major importance of an hepatoenteric pathway for the elimination of the C 19 androgen metabolites of these C 21 hormones.