The enzyme complex 3b-hydroxysteroid dehydrogenase/delta(5)-delta(4)-isomerase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. The expression of 3beta-HSD in human uterine endometrium during the menstrual cycle and decidua was examined in an effort to understand its role during ova implantation. 3beta-HSD was weakly expressed in the glandular epithelium of the proliferative phase and moderately expressed in the glandular epithelium of secretory phase of the endometrium. In the decidua of the ectopic pregnancy, 3beta-HSD was strongly expressed. The human uterine endometrial 3beta-HSD was identified as being the same type as the placental 3beta-HSD by RT-PCR and sequence analysis. In addition to the expression of 3beta-HSD, P450scc was expressed in the decidua of the ectopic pregnancy. These results suggest that pregnenolone might be synthesized from cholesterol by P450scc de novo and then, it is converted to progesterone by 3beta-HSD in the uterine endometrium. The data implies that the endometrial 3beta-HSD can use not only the out-coming pregnenolone from the adrenal gland but also the self- made pregnenolone to produce progesterone. The de novo synthesis of progesterone in the endometrium might be a crucial factor for implantation and maintenance of pregnancy.
Cholesterol/chemistry ; Cholesterol Side-Chain Cleavage Enzyme/*biosynthesis/genetics ; Decidua/enzymology ; Endometrium/*enzymology ; Female ; Gene Expression/physiology ; Human ; Menstrual Cycle/physiology ; Multienzyme Complexes/*biosynthesis/genetics ; Placenta/enzymology ; Pregnancy ; Pregnenolone/biosynthesis ; Progesterone/biosynthesis ; Progesterone Reductase/*biosynthesis/genetics ; Steroid Isomerases/*biosynthesis/genetics

The steroidal enzyme cytochrome P45017alpha catalyzes the conversion of progesterone and pregnenolone into androgens, androstenedione and dehydroepiandrosterone, respectively, the direct precursors of estrogens and testosterone. Dihydrotestosterone is the principal active androgen in the prostate, testosterone is also an active stimulant of the growth of prostatic cancer tissue. Inhibition of this enzyme as a mechanism for inhibiting androgen biosynthesis could be a worthwhile therapeutic strategy for the treatment of PCA. In this paper, four categories of steroidal inhibitors of cytochrome P45017alpha will be reviewed, a diverse range of steroidal inhibitors had been synthesized and shown to be potent inhibitors of P45017alpha.
Androstenedione ; biosynthesis ; Androstenes ; Androstenols ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Dehydroepiandrosterone ; biosynthesis ; Dihydrotestosterone ; metabolism ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Male ; Molecular Structure ; Pregnenolone ; metabolism ; Progesterone ; metabolism ; Prostatic Neoplasms ; pathology ; Steroid 17-alpha-Hydroxylase ; antagonists & inhibitors ; Testosterone ; biosynthesis