Genetic determinants of polycystic ovary syndrome: progress and future directions

Abstract

The field of the genetics of polycystic ovary syndrome (PCOS) has relatively recently moved into the era of genome-wide association studies. This has led to the discovery of 16 robust loci for PCOS. Some loci contain genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in the syndrome. The next challenge facing the field is the identification of causal variants and genes and the role they play in PCOS pathophysiology. The potential for gene discovery to improve diagnosis and treatment of PCOS is promising, though there is much to be done in the field before the current findings can be translated to the clinic.

Diagnosis, Pathogenesis and Management of Polycystic Ovary Syndrome

“…This GnRH secretion pattern leads to an increase in LH/FSH ratio [4]. The relative deficiency of FSH levels causes a decrease in aromatase activity in granulosa cells, leading to testosterone not aromatize into estrogen [18,19]. Moreover, the ovarian sex hormones have feedback effects on the nervous system, affecting the secretion of gonadotropin and the frequency of GnRH pulse [18,19].…”

“…The relative deficiency of FSH levels causes a decrease in aromatase activity in granulosa cells, leading to testosterone not aromatize into estrogen [18,19]. Moreover, the ovarian sex hormones have feedback effects on the nervous system, affecting the secretion of gonadotropin and the frequency of GnRH pulse [18,19]. Many studies have shown that low-dose E2 levels in PCOS long-term positive feedback to stimulate the hypothalamus and pituitary, leading to form high LH levels [18,19].…”

“…Moreover, the ovarian sex hormones have feedback effects on the nervous system, affecting the secretion of gonadotropin and the frequency of GnRH pulse [18,19]. Many studies have shown that low-dose E2 levels in PCOS long-term positive feedback to stimulate the hypothalamus and pituitary, leading to form high LH levels [18,19]. Androgen in women with PCOS suppresses the negative feedback effect of progesterone on GnRH pulse frequency [20,21].…”

“…In fact, PCOS is the most common cause of anovulatory infertility, the morphological changes may be genetic, but ovulation or anovulation is mainly dependent on the follicular environment, may be due to excessive production of local endocrine factor [18,28,29]. Hyperandrogenism is one of the diagnostic criteria of PCOS, and ovarian hyperandrogenism can lead to excessive follicular atresia, follicular stasis and anovulation.…”

“…In contrast, FSH mainly stimulates granulosa cells to aromatize these androgens into estrogens that is, two-cell theory [31]. In PCOS, the relative lack of FSH levels leads to a decrease in aromatase activity in granulosa cells, which prevents testosterone from converting into estrogen, while low-dose estrogen long term stimulates the hypothalamus and pituitary to form high LH levels by a positive feedback [18,19]. Progesterone is a precursor of androgen and estrogen biosynthesis.…”