Pregnenolone progesterone from

Activation of the LH receptor results in an increase of intracellular cyclic adenosine monophosphate (cAMP) levels via activation of a G protein and adenylate cyclase. In the presence of elevated concentrations of cAMP, cholesterol esterase activation occurs. This enzyme catalyzes the cleavage of cholesterol esters to free cholesterol, v/hich is then converted in mitochondria to pregnenolone as described previously. The formation of progesterone from pregnenolone is catalyzed by 5-ene-3p-hydroxysteroid dehydrogenase and 3-oxosteroid-4,5-isomerase (steps c and d in Fig. 46.3). 

The steroid Ci7(20)lyase is an enzyme that is involved in the biosynthesis of andro-stenedione and of dehydroepiandrosterone from progesterone and pregnenolone, respectively. As androgen and estrogen hormones are necessary for the growth of tumors, this enzyme is a potential therapeutic target for the treatment of prostate cancer and in hormone-dependent breast cancers. 

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

The step-by-step synthesis of the steroid hormones pregnenolone and progesterone from cholesterol (C27) was presented in chapter 20 (see fig 20.22). Note that pregneno-lone (C2i) and progesterone (table 20.4) (C2 ) are intermediates in the biosynthesis of all of the major adrenal steroids, including cortisol (C2i), corticosterone (C21), and aldosterone (C21). The same two compounds are intermediates in the synthesis of the gonadal steroid hormones, testosterone (C,9) and 17/3-estradiol (CI8). Because the synthesis of all these hormones follows a common pathway, a defect in the activity or amount of an enzyme along that pathway can lead to both a deficiency in the hormones beyond the affected step and an excess of the hormones, or metabolites, prior to that step. 

The side chain of the D ring of progesterone is removed to form testosterone, or testosterone is produced from pregnenolone via dehy-droepiandrosterone (DHEA). 

Cortisol is synthesized from pregnenolone by two pathways in the fasciculata and reticularis zones of the adrenal gland. For simplicity, only one pathway is shown in Figure 51-6. The enzyme 17a-hydroxylase and the enzyme complex A -3P-hydroxysteroid dehydrogenase A ketosteroid isomerase located in the endoplasmic reticulum will synthesize 17a-hydroxyprogesterone from either 17a-hydroxypregnenolone or progesterone. Hydroxylation of this compound by the... 

It has been shown that the fetal adrenal can convert progesterone and pregnenolone into cortisol in substantial yield (Sections 4.2.1 and 4.2.2), and, notably, Solomon (S25), after perfusion of fetuses with proges-terone-4- C, has isolated radioactive corticosterone and cortisol from the... 

Acta 27, 549 (1944) from pregnenolone Maneera et at.. J. Org. Chem. 16, [92 (1951) Pappas, Nace, J. Am. Chem. Soc. 81, 4556 (1959) by redn of allopregnane-3.20-dione with sodium borohydride Maneera et at. ibid. 75, 1286 (1953) From progesterone 20-cycloethylene ketal Soudheimer,... 

Progestins are a class of steroid hormone from which all of the other major classes of steroid hormones are derived (Figure 19.24). Progesterone is a progestin that is synthesized from pregnenolone. 

Figure 6.35. Various oxidation products reported to be formed from pregnenolone/progesterone via the action of...

In the membranes of the endoplasmic reticulum, the enzyme P450cn catalyzes the hydroxylation of C17 of progesterone or pregnenolone and can also catalyze the cleavage of the 2-carbon side chain of these compounds at C17 (a C17-C20 lyase activity). These two separate functions of the same enzyme allow further steroid synthesis to proceed along two separate pathways the 17-hydroxylated steroids that retain their side chains are precursors of cortisol (C21), whereas those from which the side chain was cleaved (C19 steroids) are precursors of androgens (male sex hormones) and estrogens (female sex hormones). 

Pregnenolone 3p-hydroxy-pregn-S-en-20-one, an intermediate in the Uosynthesis of progesterone from cholesterol, and in the biosynthesis of androgens in the adrenal cortex. See Steroids, Androgens. 

Pearlman, 1957 Vande Wide el al., 1960) >out one half of this progesterone is produced by the placenta itself. Consequently, the prc esterone produced by the placental compartment is obtmned principally (1) from pregnenolone which is synthesized via acetate or cholesterol or by hydrolysis of pregnenolone-3/S-suIfate secreted by the fetus and (2) by oxidation of 20a-dihydroprogesterone which comes principally from the fetal compartment. 

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