**3. Androgens-estrogens-pituitary secretion**

Hyperandrogenism play an important role in process of anovulation. In in-vitro study, the ovarian theca cells could increase steroidogenic activity in women with PCOS. Androgens levels originate from both ovarian and adrenal glands in PCOS. LH, ACTH, insulin and IGFs regulate production of androgen by affecting P450c17 enzyme at ovarian theca-interstitial cells and in the adrenal gland. Therefore, hyperactivity of the P450c17 enzyme represents the main mechanism resulting to ovarian hyperandrogenism that manifest in the great majority of women with PCOS. However, it is not cleared that hyperactivity of the P450c17 enzyme is a primary event or secondary to peripheral or central factors [21, 26]. Insulin is involved in hyperandrogenism from three ways. First, insulin in association with free IGF stimulates ovarian androgenesis. Second, hyperinsulinemia lead to reduce production of SHBG from liver, as a result lead to increase in free androgen level. Third, insulin may affect ovarian follicle maturation, lead to ateresia, and increase level of androgen [22].

Decrease in SHBG level affected the concentration of estron and free estradiol in women with PCOS. Due to none fluctuated production of estrogen, pituitary receive both positive feedback for LH secretion and negative feedback for secretion of FSH. As a result, the LH-FSH ratio increases. LH has pulsatile pattern. In women with PCOS, the frequency of LH secretion is increase. This change happens in response to receiving stmilution by GnRH and increase bioavailabilty of LH. The high level of LH, lead to ovarian hyperplasia and production of androgen from ovarian stromal and tecal cells. This condition fixes the chronic anovulation. It is not clear that the impairment in hypothalamic-pituitary-ovarian axis leads to PCOS or this disturbance happen as an outcome of PCOS [21, 22, 27-29].
