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• W1979751566 abstract "Studies using primary ovarian tissue and cultured human theca and granulosa cells have shown that steroidogenic enzyme activities are up-regulated in theca cells in polycystic ovary syndrome (PCOS). Although granulosa cells in arrested follicles in PCOS fail to express significant amounts of aromatase, there is an overexpression of 5α-reductase activity and premature expression of cholesterol side-chain cleavage cytochrome P450. Studies using primary ovarian tissue and cultured human theca and granulosa cells have shown that steroidogenic enzyme activities are up-regulated in theca cells in polycystic ovary syndrome (PCOS). Although granulosa cells in arrested follicles in PCOS fail to express significant amounts of aromatase, there is an overexpression of 5α-reductase activity and premature expression of cholesterol side-chain cleavage cytochrome P450. The ovarian phenotype in polycystic ovary syndrome (PCOS) is characterized by an increased number of small antral follicles aligned under a thickened capsule. These follicles are arrested in development at the stage where selection of a dominant follicle would normally occur, and the majority do not exhibit markers of atresia. The follicles frequently contain an increased number of steroidogenic cells in the theca interna, although they are not present in all follicles. There is a decreased number of granulosa cells in the arrested follicles compared with follicles of the same size in regularly cycling ovaries. Therefore, it is clear that there are abnormalities of proliferation and differentiation in both the theca and granulosa compartments of the polycystic ovary. The polycystic ovary produces abnormally high amounts of androgen. This is owing to the hyperactivity of the theca cells. The expression of LH receptors and proteins associated with steroidogenesis such as steroidogenesis acute regulatory protein (StAR), cholesterol side-chain cleavage cytochrome P450 (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17α-hydroxylase/C17-20 lyase cytochrome P450 (P450c17) is increased in the theca cells (1Jakimiuk A.J. Weitsman S.R. Navab A. Magoffin D.A. Luteinizing hormone receptor, steroidogenesis acute regulatory protein and steroidogenic enzyme messenger ribonucleic acids are overexpressed in theca and granulosa cells from polycystic ovaries.J Clin Endocrinol Metab. 2001; 86: 1318-1323Crossref PubMed Scopus (198) Google Scholar), supporting the concept that ovarian hyperandrogenism is associated with both an increased number of androgen-producing cells and an increased capacity for androgen production by each theca cell (Fig.1). P450c17 has two constituent activities, namely, the 17α-hydroxylase and the C17-20 lyase activities. The 17α-hydroxylase activity is constitutive, but the C17-20 lyase activity is dependent on phosphorylation on serine/threonine residues (2Zhang L. Rodriguez H. Ohno S. Miller W.L. Serine phosphorylation of human P450c17 increases 17,20-lyase activity implications for adrenarche and the polycystic ovary syndrome.Proc Natl Acad Sci U S A. 1995; 92: 10619-10623Crossref PubMed Scopus (397) Google Scholar). The lyase:hydroxylase ratio does not change from the unstimulated value upon stimulation of human theca cells with forskolin and insulin, alone or in combination. Because C17-20 lyase activity is not preferentially increased by hormone treatment, it appears that phosphorylation of P450c17 is not involved in hormonal regulation of ovarian androgen production. The possibility that P450c17 exhibits a higher degree of phosphorylation in certain individuals, leading to hyperandrogenism, remains to be examined. During normal follicle development the granulosa cells begin to express aromatase mRNA when the follicle grows to approximately 6–7 mm in diameter (3Jakimiuk A.J. Weitsman S.R. Brzechffa P.R. Magoffin D.A. Aromatase messenger ribonucleic acid expression in individual follicles from polycystic ovaries.Mol Hum Reprod. 1998; 4: 1-8Crossref PubMed Scopus (102) Google Scholar). In PCOS, the follicles arrest at 5–8 mm in diameter. The granulosa cells express minimal aromatase even at the larger diameters and produce very little estrogen even though androgen substrate is not limiting and there are normal concentrations of FSH bioactivity in the follicular fluid (3Jakimiuk A.J. Weitsman S.R. Brzechffa P.R. Magoffin D.A. Aromatase messenger ribonucleic acid expression in individual follicles from polycystic ovaries.Mol Hum Reprod. 1998; 4: 1-8Crossref PubMed Scopus (102) Google Scholar). The 5α-reductase activity is elevated in the granulosa cells of PCOS ovaries (4Jakimiuk A.J. Weitsman S.R. Magoffin D.A. 5α-reductase activity in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 1999; 84: 2414-2418Crossref PubMed Google Scholar), leading to markedly increased metabolism of androstenedione to 5α-androstane-3,17-dione (4Jakimiuk A.J. Weitsman S.R. Magoffin D.A. 5α-reductase activity in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 1999; 84: 2414-2418Crossref PubMed Google Scholar), a competitive inhibitor of aromatase activity. The concentration of 5α-androstane-3,17-dione in the follicular fluid of PCOS follicles is sufficient to markedly inhibit aromatase activity, whereas the concentration in the follicular fluid from control follicles is insufficient to significantly alter aromatase activity (5Agarwal S.K. Judd H.L. Magoffin D.A. A mechanism for suppression of estrogen production in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 1996; 81: 3686-3691Crossref PubMed Scopus (94) Google Scholar). This abnormality likely contributes to the failure to select dominant follicles in PCOS. In addition, the granulosa cells exhibit characteristics of luteinization. They express LH receptors and increased P450scc (1Jakimiuk A.J. Weitsman S.R. Navab A. Magoffin D.A. Luteinizing hormone receptor, steroidogenesis acute regulatory protein and steroidogenic enzyme messenger ribonucleic acids are overexpressed in theca and granulosa cells from polycystic ovaries.J Clin Endocrinol Metab. 2001; 86: 1318-1323Crossref PubMed Scopus (198) Google Scholar), suggesting that the intermediate stages of granulosa cell differentiation that normally occur during the late follicular phase are bypassed in PCOS." @default.
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• W1979751566 date "2006-07-01" @default.
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• W1979751566 title "Ovarian enzyme activities in women with polycystic ovary syndrome" @default.
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• W1979751566 doi "https://doi.org/10.1016/j.fertnstert.2006.03.015" @default.
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