Table 1 Changes in steroidogenesis observed in PCOS and PCOS models
From: Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS
Study | Subjects, animals, or cell line | Intervention/gene quantification | Outcome |
|---|---|---|---|
Li et al., 2013 [46] | - PCO-like hyper androgenic rat (Sprague Dawley rat) model induced by insulin and hCG injections | - P450scc (CYP11A1) and CYP17A1 gene expression in ovarian theca cells - Ovarian morphology - Changes in estrous cycle - Ovarian androgen production | - Elevated expression of P450scc in thecal and stromal cells - Elevated CYP17A1 gene expression - Reduced granulosa cell layers and augmented theca cell layers with multiple large cysts - Abnormal estrous cyclicity - Elevated androstenedione and T levels |
Franks et al., 1997 [32] | - Symptomatic women with PCOS (polycystic ovaries on ultrasound and symptoms) (n = 97) - Asymptomatic PCOS (polycystic ovaries on ultrasound and no symptoms) (n = 51) - No PCOS with normal ovaries on ultrasound (n = 59) | - Genotype analysis of CYP11A1 using microsatellite marker in the promoter region - Non-parametric linkage analysis in CYP11A1 region using polymorphic markers | - Excess allele sharing/linkage at the CYP11A1 locus with a non-parametric linkage score of 3.03 (probability of CYP11A1 gene being linked to PCOS) - CYP11A1 as a major genetic susceptibility locus for PCOS |
Wickenheisser et al., 2012 [44] | - Women with PCOS (n = 5), defined by NIH consensus guidelines - Women without PCOS (n = 5) | - CYP11A1 gene expression at transcriptional and post-transcriptional level using RT-PCR, mRNA degradation studies, and functional promoter analyses - Basal and cAMP-dependent CYP11A1 promoter function - CYP11A1 mRNA half-life - Expression of CYP17A1 gene | - Increased CYP11A1 promoter activity and steady state CYP11A1 mRNA abundance in both basal and forskolin stimulated conditions in PCOS theca cells - More than 2-fold increase in CYP11A1 mRNA half-life - Increased basal mRNA stability in PCOS ovarian theca cells - Increased expression of CYP17A1 gene at both transcriptional and post-transcriptional level in PCOS |
Liu et al., 2011 [45] | - Women with PCOS (n = 12) who underwent laparoscopic ovarian wedge resection - Control women (n = 12) who underwent contralateral ovarian biopsy | - Expression of CYP11A1 mRNA and protein levels using RT-PCR and Western blot analyses | - Higher CYP11A1mRNA and protein levels in PCOS group |
Sander et al., 2011 [31] | - Women with (n = 28) PCOS and without (n = 28) PCOS who underwent IVF | - CYP11A1 mRNA expression levels in luteinized granulosa cells - Follicular fluid E2 and P4 levels - StAR and 3β-HSD mRNA expression in granulosa cells | - No change in CYP11A1 mRNA expression levels in granulosa cells between two groups - Significantly lower E2 and P4 levels in the follicular fluid of women with PCOS - Increased expression of StAR mRNA levels in women with PCOS - No change in 3β-HSD mRNA expression in polycystic ovaries |
Hogg et al., 2012 [49] | - 11 months-old female offspring of ewe PCO-model induced by prenatal testosterone propionate (TP) (n = 9) - Age-matched control ewe (n = 5) | - StAR gene expression - Androstenedione levels | - Enhanced androstenedione secretion in the antral follicles of PCO-like ewe that was augmented after treatment with recombinant LH - Higher thecal LH receptor gene expression - Increased number of estrogenic follicles - Up-regulation in StAR mRNA expression in theca cells |
Jakimiuk et al., 2001 [34] | - Women with PCOS (n = 12) undergoing electrocauterization of the ovarian surface or wedge resection of the ovaries, - Age-matched control (n = 24) premenopausal women undergoing total abdominal hysterectomy with bilateral oophorectomy for non-ovarian indications | - Expression of StAR, CYP17A1, CYP11A1 and LH receptor mRNA | - Elevated expression of StAR, CYP17A1, CYP11A1, and LH receptor mRNA in the theca cells of women with PCOS - Increased LH receptor and CYP11A1 expression in granulosa cells of women with PCOS |
Kahsar-Miller et al., 2001 [50] | - Women with PCOS (n = 7) - Control women (n = 10) | - StAR expression - Ovarian morphology | - Significantly higher number of follicular cysts and staining for StAR immunoreactivity in theca cell of women with PCOS |
Nelson et al., 1999 [51] | - Normal and PCOS theca interna cells | - CYP17A1, CYP11A1, and 3β-HSD mRNA and protein levels - P4, 17OHP, and T levels | - Increased production of P4, 17OHP, and T by theca cells of women with PCOS - Elevated CYP17A1, CYP11A1, and 3β-HSD mRNA and protein levels in theca cells of women with PCOS - No difference in StAR mRNA expression |
Wickenheisser et al., 2000 [55] | - Theca cells of women with or without PCOS | - CYP17A1 and StAR promoter activity | In PCOS theca cells: - Four-fold greater CYP17A1 promoter activity - Augmented basal and cAMP-dependent CYP17A1 gene expression - Slower degradation of CYP17A1 mRNA - No change in StAR promoter activity |
Doldi et al., 2000 [57] | - Women with (n = 10) and without (n = 10) PCOS | - 3β-HSD mRNA expression | - Lower expression of 3β-HSD mRNA in PCOS granulosa cells obtained from follicles measuring ≤ 10 mm and > 16 mm |
Erickson et al., 1979 [70] | - Granulosa cells from normal and polycystic ovaries | - Ability of granulosa cells to aromatize androgens after in vitro incubation of granulosa cells with androstenedione, FSH and LH | - Elevated E2 production in granulosa cells from normal (8–15 mm) follicles - Negligible E2 production by granulosa cells from small (4–6 mm) follicles of both normal and polycystic ovaries - 17–24 fold increase in E2 production in PCOS and control ovaries in response to FSH - Little or no effect on E2 production by addition of LH |
Pierro et al., 1997 [64] | - Granulosa luteal cells from polycystic and normal ovaries | - Effect of atamestane (aromatase inhibitor) on granulosa luteal cells | - Robust inhibition of basal aromatase activity after treatment with atamestane in both groups with more pronounced effect in cells of normal ovaries in comparison to cells of PCOS ovaries |
Andreani et al., 1994 [71] | - Granulosa cells from polycystic ovaries and normal ovaries in the preovulatory phase after oocyte retrieval during GIFT | - E2 and P4 production in the presence or absence of FSH | - 2–3 fold increase in E2 production in PCOS ovaries after FSH treatment - No change in P4 production after FSH treatment |
Mason et al., 1994 [65] | - Granulosa cells from normal, ovulatory and anovulatory polycystic ovaries | - FSH-induced E2 production - Follicular androstenedione levels | - Significantly higher androstenedione in small follicles (5–11 mm) from ovulatory PCOS - 6–10 times higher FSH-induced E2 response in anovulatory PCOS |
Söderlund et al., 2005 [72] | - Women with PCOS (n = 25), - Women without PCOS (n = 50) | - PCR analysis of genomic DNA and complete sequence of all exons of the aromatase gene and its promoter | - Mutations of the P450arom gene or its promoter were not found to be associated with PCOS |