Expression of Messenger Ribonucleic Acid Species Encoding Steroidogenic Enzymes in Human Follicles and Corpora Lutea throughout the Menstrual Cycle*

Abstract

The levels of expression of mRNA species encoding cholesterol side-chain cleavage cytochrome P-450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P450(17 alpha], aromatase cytochrome P-450 (P-450AROM), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) were examined in human follicles and corpora lutea (CL) throughout the menstrual cycle. Tissues were obtained from women undergoing hysterectomy and oophorectomy. The largest follicle or the CL was dissected from the ovary depending on whether the surgery was performed in the follicular or luteal phase. The day of the cycle was determined by onset of last menstrual period and was confirmed by endometrial histology. Total RNA was examined by Northern blot analysis, using as probes specific 32P-labeled cDNA inserts encoding each human enzyme. Early follicles demonstrated detectable mRNA for both P450scc and P450(17 alpha), but not for P450AROM or 3 beta HSD. P450AROM was detectable late in the follicular phase and appeared markedly induced in the CL. 3 beta HSD was detectable only in the CL. Levels of P450(17 alpha) mRNA remained relatively unchanged throughout the cycle, whereas P450scc mRNA levels were greatly increased in the CL. The presence of P450(17 alpha) mRNA in the human CL is of interest, since it is absent from the bovine CL, and this is consistent with the ability of the human, but not the bovine, CL to synthesize 17 alpha-hydroxyprogesterone and estrogens. The fact that P450AROM expression is highest in CL is surprising, since plasma estrogen levels are highest during the late follicular phase of the cycle, and may suggest that CL estrogen biosynthesis is limited by 17 alpha-hydroxylase or 17,20-lyase activities.

The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

“…60). It is clear that the temporal and spatial specific expression of this gene is required for steroid synthesis, which is necessary for many physiological processes (6,10,(61)(62)(63). However, relatively little is known about the mechanism(s) of its regulation and the factors involved therein.…”

“…The enzyme P450scc is encoded by a single human gene, CYP11A1 (2), on chromosome 15q23-24 (3), and its expression is regulated hormonally at the transcriptional level (4). Although expression of the gene has been detected in the central nervous system (5), P450scc transcript and protein are expressed for the most part in steroidogenic tissues such as adrenals, ovaries (6), testis, and the placenta (7)(8)(9). The hormonal regulation and developmental pattern of expression of P450scc are species-and tissue-specific (10).…”

Aromatase expression in the ovary: Hormonal and molecular regulation

“…In humans, estrogen levels also undergo a transient decline after the gonadotropin surge and a later increase due to marked induction of aromatase mRNA [93]. In contrast, in cattle, this gene remains expressed at very low levels during pregnancy [94,95].…”

Effect of cell-plating density on the steroidogenic activity of human cumulus cells

“…In granulosa cells, an increase either in the enzymes cholesterol side-chain-cleavage, cytochrome P-450 (P-450scc), 3 ß-hydroxysteroid dehydrogenase and aromatase cytochrome P-450, or in the secretion of progesterone by follicular cells is observed following the LH surge in the newly formed corpus luteum (Sano et al, 1981;Sasano et al, 1989;Doody et al, 1990). In cumulus cells, the increase in P-450scc activity occurs only in cumulus-oocyte complexes in which the oocyte has undergone germinal vesicle breakdown (Goldschmit et al, 1989).…”