CYP17 genotype modifies the impact of anthropometric variation on salivary estradiol in healthy women

Abstract

Several studies demonstrate that human ovarian function is responsive to the energetic environment, which has led to the development of theoretical models that explain this phenomenon. Although many genes are involved in ovarian hormone production, the possibility that genetic polymorphism may affect ovarian response to energetic conditions has not been considered. Cytochrome P450c17α is an enzyme that produces androgen precursors used to make estrogens during ovarian steroidogenesis, and is encoded by the CYP17 gene. A functionally significant variant within the promoter region of CYP17 has been linked to variation in steroid production, and some evidence suggests that this polymorphism could alter transcription of CYP17 in an insulin-dependent manner. We tested the hypothesis that the CYP17 variant affected the relationship between anthropometric measurements and salivary estradiol in healthy women in the United States (n = 28). PCR-RLFP analysis was used to genotype women for the genetic variant, and estradiol was assayed from saliva by EIA. Moderated regression analysis of these preliminary data revealed a significant interaction between waist-to-hip ratio and CYP17 genotype (P = 0.004). Our study provides evidence that gene-environment interactions should be considered in future adaptive models for human ovarian function. Moreover, our results stand to illuminate possible associations between this genetic variant and reproductive disease.

Increased mood symptoms in postmenopausal women related to the polymorphism rs743572 of the CYP17 A1 gene

“…Mutations of the CYP17 A1 gene have been related to 17a-hydroxylase deficiency, 17 alpha-hydroxylase/17,20-lyase deficiency, adrenal hyperplasia, and pseudohermaphroditism. Some CYP17 polymorphisms have been linked to variation in steroid hormone production [19]. Although we did not measure steroid hormones, it could be possible that among our postmenopausal women this GG genetic variant be linked to lower estradiol production from androgen precursors or dysfunction at the estrogenic receptor level and therefore present more intense symptoms related to the menopause, especially those involving mood.…”

Bone Morphogenetic Protein 15 (BMP-15) Improves In Vitro Mouse Folliculogenesis

“…Additionally, BMP-15 supplementation had no effect on the expression of the CYP17 gene. An enzyme known as cytochrome P450c17, which is encoded by the CYP17 gene, produces androgen precursors that turn into estrogens during ovarian steroidogenesis [ 45 ]. Presumably, in the theca interna cells, the P450 enzyme (CYP11A1) converts cholesterol into pregnenolone within the mitochondrial inner membrane [ 46 ].…”