Pregnenolone formation

Acetoxy-l-nonanoic add, 811 N-Acetoxyphthalimide, 9 21-Acetoxypregnane-3,ll,20-trione, 524 17a-Acetoxy-A -pregnene-3d-ol-20-one, 318 17a-Acetoxy-A -pregnenolone formate, 36-... 

We investigated the effect of homogeneous rat liver SCP2 on this process [33]. As shown in Fig. 4, the utilization of lipid droplet cholesterol for pregnenolone formation by adrenal mitochondria was dramatically increased by the addition of homogeneous SCP2. This effect was concentration dependent, and it was not mimicked by the addition of albumin. 

When stimulation of the normal activity of the target tissue requires increased synthesis of key enzymes, intracellular effects of cyclic 3, 5 -AMP have been suggested to take place either at the translation level, as in the stimulation by ACTH of the synthesis of enzymes involved in pregnenolone formation from cholesterol, or at the transcription level, as in the stimulation by TSH of iodide transport in the thyroid. The main evidence for stimulation at the transcription level is the inhibition of the effect by both inhibitors of RNA synthesis (as actinomydn) and of protein synthesis (as puromycin), while stimulation at the translation level is suggested by inhibition with protein-synthesis inhibitors, but not with RNA-syn-tbesis inhibitors. Effects of 3, S -AMP on amino-acid incorporation in acellular systems, and on peptide release by polysomes have been reported, but their relevance to the activation at the translation level of protein synthesis in the intact cell is not known. 

Stoichiometry of C,-Compounds and Pregnenolone Formation from Cholesterol ... 

Pregnenolone Formation from Cholesterol and Some of Its Oxygenated Derivatives by a Soluble Bovine Adrenocortical Mitochondrial Preparation ... 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

C28H,40 21307-05-1) see Ergocalciferol (3p)-pregna-5,16,20-triene-3,20-diol 20-acetate 3-formate (C24H22O4 62490-12-4) see Desoxycortone acetate pregnenolone... 

Cytochrome PTSOiy, carries out comparable reactions for removal of the side chain of pregnenolone, and two reactions have been described both of which involved loss of acetate—17a-hydroxylation and formation of the 17-keto compound, and direct formation of the A -ene (Figure 3.19c) (Akhtar et al. 1994). 

Since the predatory water beetles cannot biosynthesise the steroid skeleton de novo, steroidal precursors must be obtained from exogenous sources. Bacillus-strains, isolated from the foregut of the water beetle Agabus affinis, were tested for their ability to transform steroids [101]. After incubation with androst-4-en-3,17-dione two Bacillus strains produced 13 different transformation products. Hydroxylation took place at C6, C7, Cll and C14 resulting in the formation of 6fi-, 7a-, 1 la-, and 14a-hydroxyandrost-4-en-3,17-diones. After incubation with pregnenolone the two Bacillus strains produced a variety of steroids among which 7a-hydroxypregnenolone was the major product [102]. 

An important transformation in steroid biochemistry is the conversion of pregnenolone into progesterone. Progesterone is a female sex hormone, a progestogen, but this reaction is also involved in the production of corticosteroids such as hydrocortisone and aldosterone. The reaction also occurs in plants, and features in the formation of cardioactive glycosides, such as digitoxin in foxglove. 

Fig. 5. Pattern of product formation during single turnover cycles of anaerobic reduction/oxygenation of the cytochrome P-450,.,. - cholesterol - adrenodoxin complex. The results are expressed as a percentage conversion of the total [14C]cholesterol added to the incubation. Cholesterol, o 22-hydroxy-cholesterol, 20,22-dihydroxycholesterol. a pregnenolone, (from Ref. 38, with permission).

The rate of total steroidogenesis is determined by the rate of supply of cholesterol to cytochrome P-450scc. The rate of flux through this step determines the rate of synthesis of the sum of the steroid products, but does not determine the rate of synthesis of any individual steroid. The pattern of steroidogenesis, i.e. which steroids are produced and in what ratio, is determined by the relative activities of the enzymes of the steroidogenic pathway beyond the formation of pregnenolone. 

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