The synergistic effect of sex hormone-binding globulin and aromatase genes on polycystic ovary syndrome phenotype

被引:28
作者
Xita, Nectaria [1 ]
Georgiou, Ioannis [2 ]
Lazaros, Leandros [2 ]
Psofaki, Vasiliki [3 ]
Kolios, George [3 ]
Tsatsoulis, Agathocles [1 ]
机构
[1] Univ Ioannina, Dept Endocrinol, GR-45110 Ioannina, Greece
[2] Univ Ioannina, Lab Human Reprod Genet, GR-45110 Ioannina, Greece
[3] Univ Hosp Ioannina, Biochem Lab, Ioannina 45110, Greece
关键词
D O I
10.1530/EJE-07-0905
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Experimental evidence suggests that fetal exposure to androgen excess may program the development of polycystic ovary syndrome (PCOS) in utero. The aim of this study was to examine whether the sex hormone binding globulin (SHBG)(TAAAA)n and the cytochrome P450. family 19 (CYP19)(TTTA)n polymorphisms, known to influence sex hormone-binding globulin (SHBG) levels and aromatase activity respectively. play a synergistic role in the development of PCOS. Design and methods: We studied 180 women with PCOS and 160 healthy women of reproductive age. The body mass index (BMI) was recorded and the hormonal profile determined from the third to fifth day of menstrual cycle. DNA was extracted from blood leucocytes and the SHBG(TAAAA)n and CYP19(TTTA)n polymorphisms were genotyped. Results: Genotype analysis revealed 6 SHBG(TAAAA)n alleles with 6-11 repeats and 6 CYP19(TTTA)n alleles with 7-12 repeats. Women were subdivided into four groups: those with short SHBG (<= 8 TAAAA repeats) and CYP19 alleles (<= 9 TTTA repeats), those with short SHBG-long CYP19 alleles, those with long SHBG-short CYP19 alleles, and those with long SHBG and CYP19 alleles. Women with PCOS tended to have at greater frequency, long SHBG-short CYP19 alleles compared with controls (57.3 vs 42.4%, P=0.07). Importantly. PCOS women with long SHBG-short CYP19 alleles had the lowest SHBG levels (P=0.02) and the highest total testosterone (P=0.008), free androgen index (P=0.002). DHEAS (P=0.02), and testosterone/estradiol ratio (P=0.03), compared with those with other genotypes. This association was independent of age. BMI, and insulin resistance indexes. Conclusion: We speculate that the SHBG and CYP19 genes may have a synergistic role in the developmental programming of PCOS, by affecting androgen bioavailability and aromatization respectively.
引用
收藏
页码:861 / 865
页数:5
相关论文
共 26 条
[1]   Developmental origin of polycystic ovary syndrome - a hypothesis [J].
Abbott, DH ;
Dumesic, DA ;
Franks, S .
JOURNAL OF ENDOCRINOLOGY, 2002, 174 (01) :1-5
[2]   The CYP19 gene and associations with a androgens and abdominal obesity in premenopausal women [J].
Baghaei, F ;
Rosmond, R ;
Westberg, L ;
Hellstrand, M ;
Eriksson, E ;
Holm, G ;
Björntorp, P .
OBESITY RESEARCH, 2003, 11 (04) :578-585
[3]   Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene [J].
Belgorosky, A ;
Pepe, C ;
Marino, R ;
Guercio, G ;
Saraco, N ;
Vaiani, E ;
Rivarola, MA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (11) :5127-5131
[4]   Estrogen actions in the ovary revisited [J].
Britt, KL ;
Findlay, JK .
JOURNAL OF ENDOCRINOLOGY, 2002, 175 (02) :269-276
[5]   Aromatase deficiency in women and men: Would you have predicted the phenotypes? [J].
Bulun, SE .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (03) :867-871
[6]  
CLARK AF, 1975, FERTIL STERIL, V26, P1001
[7]   Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women [J].
Cousin, P ;
Calemard-Michel, L ;
Lejeune, H ;
Raverot, G ;
Yessaad, N ;
Emptoz-Bonneton, A ;
Morel, Y ;
Pugeat, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (02) :917-924
[8]   POLYCYSTIC-OVARY-SYNDROME AS A FORM OF FUNCTIONAL OVARIAN HYPERANDROGENISM DUE TO DYSREGULATION OF ANDROGEN SECRETION [J].
EHRMANN, DA ;
BARNES, RB ;
ROSENFIELD, RL .
ENDOCRINE REVIEWS, 1995, 16 (03) :322-353
[9]   The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome [J].
Ferk, Polonca ;
Teran, Natasa ;
Gersak, Ksenija .
HUMAN REPRODUCTION, 2007, 22 (04) :1031-1036
[10]  
GABRILOVE J. L., 1964, J MOUNT SINAI HOSP, V31, P449