Female prepubertal rats were treated with equine chorionic gonadotropin (eCG) to induce folliculogenesis, together with dehydroepiandrosterone (DHEA) to induce hyperandrogenism and/or PGZ to evaluate PPARG activation.
To test the hypothesis that the triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIRAN syndrome) in the presence of obesity, also known as type C insulin resistance, is caused by mutations in the gene for peroxisome proliferator activated receptor gamma (PPARgamma), a receptor for the thiazolidinedione drugs that enhance sensitivity to insulin.
Two hypermethylated CpG sites in the PPARG1 promoter and five hypomethylated CpG sites in the NCOR1 promoter were observed only in HA PCOS women (P < 0.01 to P < 0.0005).
Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.
This SHBG decrease is more pronounced in girls with premature pubarche who are at risk to develop functional ovarian hyperandrogenism as well as insulin resistance syndrome.
These results were confirmed by a multiple regression analysis model in which adrenal hyperandrogenism was negatively associated with age (<i>P</i> < 0.001) and SHBG concentrations (<i>P</i> = 0.02), but not with any metabolic parameter.
Women with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress, as well as biochemical evidence of hyperandrogenism (higher dehydroepiandrosterone sulfate and lower SHBG) and a trend toward more clinical signs of hyperandrogenism (hirsutism).
Serum androgen, IGFBP-1, and SHBG concentrations; IRS-1 genotypes.Twenty-five of 54 (45%) girls with a history of PP developed hyperinsulinemic ovarian hyperandrogenism at adolescence.
In addition, the results support previous findings in which heterozygous CYP21 mutations are associated with symptoms of hyperandrogenism in susceptible individuals.
The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated.
Depending on CYP21A2 genotype, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to biochemical alterations (including hyperandrogenism, hypocortisolism, and hypoaldosteronism) and a wide spectrum of phenotypic disease manifestation.
Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels.
Biological hyperandrogenism was found in the prepubertal CYP21A2 mutation carriers, whereas the four heterozygous girls who were followed long enough to have reached pubertal age presented biological and clinical hyperandrogenism.
A reduction in plasma sex hormone-binding globulin (SHBG), a transport carrier that binds estrogen and androgens and regulates their biological activities, is often used as an indicator of hyperandrogenism in women with PCOS.
We have hypothesized that heterozygosity for CYP21 mutations in women increases their risk of developing clinically evident hyperandrogenism, and that this risk is related to the severity of the mutation of CYP21 and/or the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation.
The frequency of heterozygosity for CYP21 mutations was increased in women with symptomatic hyperandrogenism (10/30) compared to healthy controls (1/14).
According to reduced sex hormone-binding globulin levels and increased free androgen index in the present study, obesity was linked with hyperandrogenism in female subjects.