The comparison of miR-130b-3p in normal and PCOS theca cells demonstrated decreased miR-130b-3p expression in PCOS theca cells, which was correlated with increased DENND1A.V2, cytochrome P450 17α-hydroxylase (CYP17A1) mRNA and androgen biosynthesis. miR-130b-3p mimic studies established that increased miR130b-3p is correlated with decreased DENND1A.V2 and CYP17A1 expression.
Phospho-ERK1/2 in granulosa cells can be correlated with reduced Cyp17a1 expression in theca cells, and the interaction between granulosa and theca cells may be impaired in PCOS-model mice.
In view of the strong evidence implicating the importance of CYP19A1 and CYP17A1 in androgen metabolic pathways, we investigated the association of rs700519, rs2414096, and rs743572 (- 34T>C) polymorphisms on susceptibility of developing PCOS, in North India.
Cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene encodes a key enzyme in the synthesis and metabolism of steroid hormones and has been associated with various factors, such as hypertension, insulin resistance, and polycystic ovary syndrome.
Enzyme activity evaluation showed that lean PCOS had increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P < 0.001), P450aro (P < 0.001), 3βHSD2 (progesterone/ pregnenolone and 17-OHP/17-hydropregnenolone, both P < 0.001) and decreased activity of P450c21(11-deoxycorticorsterone/progesterone and 11-deoxycortisol/17-OHP, P < 0.001).
AMH decreases androgen biosynthesis by inhibiting CYP17 activity; a potential mechanism of action for AMH variants in PCOS, therefore, is to increase androgen biosynthesis due to decreased AMH-mediated inhibition of CYP17 activity.
C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients.
No significant association between CYP17-34T/C polymorphism and IR was found in Thai PCOS women, although the A2/X genotype group was statistically significantly younger than the A1/A1 genotype group.
The CYP17A1 gene -34T/C polymorphism might not be directly correlated with the PCOS, but might influence PCOS via the association of testosterone level and the HOMA-IR.
Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP17 polymorphism and PCOS were calculated in a fixed-effects model and a random-effects model when appropriate.
Our study carried out in a defined group of Indian women with PCOS suggests for the first time an individual, as well as combined, association of polymorphisms in CYP11A1 and CYP17 promoters with T levels.
DNA samples from forty-four adolescent girls with PCOS and 50 healthy controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the genotypic frequency of 17 different polymorphic loci on the FSHR (A307T, N680S), CYP17 (-34 T/C), CYP1A1 (T6235C), CAPN10 (44, 43, 19, 63), INSR (exon 17 C/T), SERPINE1 (4G/5G) genes.
Polymorphism T --> C (-34 base pairs) of gene CYP17 promoter in women with polycystic ovary syndrome is associated with increased body weight and insulin resistance: a preliminary study.
We hypothesize that c-fos expression inhibits 17alpha-hydroxylase 17,20 lyase (CYP17) activity in the human ovary, and its decreased expression seen in PCOS may lead to elevated CYP17 transcription, resulting in increased androgen production.
We hypothesize that c-fos expression inhibits 17alpha-hydroxylase 17,20 lyase (CYP17) activity in the human ovary, and its decreased expression seen in PCOS may lead to elevated CYP17 transcription, resulting in increased androgen production.
These studies indicate that a slower rate of CYP17 mRNA decay contributes to increased steady-state mRNA accumulation and augmented CYP17 gene expression in PCOS theca cells.
Scanning mutant analysis demonstrated that mutations within a 16-bp sequence, spanning -174 to -158 bp of the promoter, ablated increased basal CYP17 promoter function in PCOS theca cells.
It does not appear that this common variant of CYP17, a T to C substitution in the 5' promoter region, plays a significant role in the adrenal androgen excess of PCOS.
Characterization of PCOS theca cells demonstrated that elevated expression of the steroidogenic enzymes 17alpha hydroxylase/17,20 lyase (CYP17) and P450 side chain cleavage enzyme (CYP11A1) play a role in increased androgen production by 3beta-hydroxysteroid dehydrogenase in the PCOS theca cell.
Examination of the metabolism of radiolabeled steroid hormone precursors and steady-state levels of mRNAs encoding steroidogenic enzymes revealed that there are multiple alterations in the steroidogenic machinery of PCOS theca cells, including elevated expression of the CYP11A, 3BHSD2, and CYP17 genes.