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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
  1. Abbreviations: PCOS polycystic ovary syndrome, FSH Follicle-stimulating hormone, LH luteinizing hormone, P450scc cholesterol side-chain cleavage enzyme, StAR steroidogenic acute regulatory protein, 3β-HSD 3beta-hydroxysteroid dehydrogenase, CYP17A1 17α-hydroxylase, hCG human chorionic gonadotropin, T testosterone, IVF in vitro fertilization, GIFT gamete intra-fallopian transfer, E2 estradiol, P4 progesterone, RT-PCR reverse transcription-polymerase chain reaction, 17OHP 17-hydroxyprogesterone