OBJECTIVE: To determine whether the ovary influences adrenal androgen secretion in women with polycystic ovary syndrome (PCOS). DESIGN: Six PCOS-affected patients with clomiphene resistance and gonadotrophin hyperresponsivity, and six controls with regular ovulatory cycles, matched for age and body mass index. METHODS: Bilateral ovarian wedge resection was performed to induce ovulation surgically for these refractory women with PCOS. The adrenal androgen secretions were evaluated in PCOS patients before and again 6 months after this surgery, and in the controls, using an ACTH stimulation test (0.25mg synthetic ACTH(1-24)). RESULTS: Biochemically, basal levels and the maximum net increases (Delta) of 17-hydroxyprogesterone (17-OHP) and androstenedione, Delta17-OHP/Delta progesterone and Delta androstenedione/Delta17-OHP ratios in response to exogenous ACTH were significantly higher in PCOS patients before operation than those of controls. This purely ovarian surgery in women with PCOS was found to significantly reduce their basal androstenedione, testosterone and LH levels, insulin/glucose ratio, and post-corticotrophic Delta17-OHP, Delta androstenedione, Delta17-OHP/Delta progesterone and Delta androstenedione/Delta17-OHP, without obvious changes in FSH, oestradiol, sex hormone-binding globulin, Delta dehydroepiandrosterone, Delta dehydroepiandrosterone sulphate, Delta aldosterone and Delta cortisol values. CONCLUSIONS: Ovarian hyperandrogenicity from polycystic ovary may contribute to the enhanced adrenal P450c17alpha activity and subsequent Delta(4) androgen reserve revealed by the pharmacological corticotrophin stimulation in our special PCOS cases.
XK Wu, SY Zhou, K Sallinen, P Pollanen and R Erkkola
Z Gombos, R Hermann, R Veijola, M Knip, O Simell, P Pollanen and J Ilonen
OBJECTIVE: Animal models suggest that androgen receptor gene polymorphisms might affect disease predisposition in human immune-mediated diabetes. The aim of this study was to investigate the effect of the human androgen receptor gene exon 1 CAG repeat polymorphisms on type 1 diabetes (T1D) susceptibility. DESIGN AND METHODS: A combined strategy of case-control and family-based approaches was used. Affected sibling pair families (n=120), nuclear families (n=645) and cohorts of sporadic cases (n=208) and controls (n=1381) were genotyped for androgen receptor gene exon 1 CAG repeat polymorphism. An automated fluorescence-based DNA fragment-sizing method was used. RESULTS: The distribution of CAG repeat alleles did not differ significantly between patients and controls. However, short repeat alleles (7-14) were more prevalent among cases in girls compared with controls (8.77% vs 5.91%; P=0.03). Long repeat alleles (19-28) were less frequent among HLA DR3-positive diseased boys than in DR3-positive control boys (32.6% vs 40.6%; P=0.011). The differences were not significant after adjustment for multiple comparisons. Transmission of CAG repeat alleles was not different from expected in the total material. However, transmissions to girls deviated from the expected value significantly (extended transmission disequilibrium test (ETDT) 37.82; P=0.0016). A decreased transmission of the alleles with 13, 20 and 26 repeats to girls was observed (T%0, P=0.046; T%25.5, P=0.0003, T%0, P=0.025). CONCLUSION: The results do not support a common role for the androgen receptor gene exon 1 CAG repeat in T1D susceptibility; however, an effect of a disease variant in linkage disequilibrium could be detected.