The pathogenesis of polycystic ovary syndrome: Lessons from ovarian stimulation studies

Abstract

In polycystic ovary syndrome (PCOS) the ovary produces markedly increased amounts of both androgens and estrogens in response to gonadotropin stimulation. Distinctive responses of 17-hydroxyprogesterone and androstenedione to ovarian stimulation testing suggest that ovarian hyperandrogenism is a result of dysregulation of theca cell androgen production which is intrinsic to the ovary. The occurrence of hyperestrogenism together with hyperandrogenism in PCOS suggests that whatever the abnormality of local regulatory factors of steroidogenesis, it affects granulosa as well as theca cells. Dysregulation is often associated with an increase in the number of follicles which evade atresia and reach the 2-8 mm stage of development. Autocrine/paracrine factors, especially those which are FSH-dependent, likely play an important role in the pathogenesis of the ovarian abnormality. Both LH and insulin hypersecretion probably play a secondary role in PCOS by amplifying the preexisting ovarian dysregulation. Because FSH secretion is under tight long-loop negative-feedback control and LH is not, hyperandrogenism is the primary clinical manifestation of dysregulation of steroid production in PCOS. However, anovulation in PCOS is most likely a result of excessive estrogen and inhibin production by multiple, small follicles which inhibit FSH secretory dynamics sufficiently to prevent selection of a dominant follicle.

Obesity and the polycystic ovary syndrome

“…Indeed, some in vitro studies have demonstrated that inhibin stimulates ovarian androgen production. 39 As reported above, a phosphorylation of serine residues of the insulin receptor 15 may be a factor leading to insulin insensitivity and, therefore, compensatory hyperinsulinemia in PCOS women. Interestingly, the same disorder seems to be responsible for the increased activity of the human P450c17 system as well.…”

Evaluation of ovarian and metabolic effects of GnRH modulators in two rat models of polycystic ovary syndrome

“…Hyperandrogenism is the primary clinical manifestation of dysregulation of steroid production in patients with PCOS (Barnes, 1998). LH hypersecretion and hyperinsulinemia synergistically increases androgen production (Jayasena & Franks, 2014).…”

Vitamin D3 regulates steroidogenesis in granulosa cells through AMP‐activated protein kinase (AMPK) activation in a mouse model of polycystic ovary syndrome

“…38 Some of the published reports revealed the effects of vitamin D3 on the regulation of steroidogenesis pathway in human granulosa cells. 41,42 It is determined that androgen excess in hyperandrogenic PCOS women could disturb steroidogenesis pathway which subsequently leads to disruption in follicular development. Disturbance in this process could create ovulatory problems and infertility like that seen in PCOS women.…”

“…Disturbance in this process could create ovulatory problems and infertility like that seen in PCOS women. 41,42 It is determined that androgen excess in hyperandrogenic PCOS women could disturb steroidogenesis pathway which subsequently leads to disruption in follicular development. 3,43,44 In the present study, we induced PCOS mice model by DHEA to mimic the human anovulatory PCOS and investigated the mechanism of action of vitamin D3 on steroidogenesis process in granulosa cells of the polycystic ovary.…”