Defects in insulin signaling pathways in ovarian steroidogenesis and other tissues in polycystic ovary syndrome (PCOS)

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Abstract

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age today. Women with PCOS often demonstrate defective ovarian steroid biosynthesis and present with hyperandrogenemia. Moreover, 50–70% of PCOS women are insulin resistant and hyperinsulinemic. Insulin acts on the ovary via its own receptor and interacts with gonadotrophins, modulating steroidogenesis. The precise role of insulin and the molecular mechanisms that take place are not yet completely explicated. This review will be focused on insulin's action on the ovary and other target tissues, describing the intracellular signaling pathways implicated in steroidogenesis and their defects in women with PCOS.

Section snippets

Peripheral tissues

The molecular mechanisms underlying insulin resistance in peripheral tissues in PCOS remain under intensive investigation. Fibroblast cultures have been used in an attempt to exclude environmental factors influencing the insulin action in them. The number and the affinity of the insulin receptors have been found normal in adipose tissue, both [13], [14], [15] in muscle [16], [17] and fibroblast cells [18], [19] from PCOS patients. Isolated adipocytes from PCOS women showed a significant

Ovaries

Cholesterol is the universal substrate for steroid biosynthesis. LDL is the major source of cholesterol in humans and is transported into ovarian cells via the LDL receptor pathway [27]. It has been found that in cultures of granulosa cells, gonadotrophins stimulate LDL receptor protein and gene expression [28], [29], [30]. Interestingly, insulin adds to this action of LH and FSH [31]. It is noteworthy to clarify the mediatory role of LH and insulin to the regulation of LDL receptor gene

References (48)

  • A. Dunaif

    Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis

    Endocrine Reviews

    (1997)
  • A. Dunaif et al.

    Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome

    Diabetes

    (1989)
  • A. Dunaif et al.

    The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome

    The Journal of Clinical Endocrinology and Metabolism

    (1996)
  • J.E. Nestler et al.

    Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome

    The New England Journal of Medicine

    (1996)
  • J.E. Nestler et al.

    Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens

    The Journal of Clinical Endocrinology and Metabolism

    (1997)
  • J.E. Nestler et al.

    Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome

    The New England Journal of Medicine

    (1998)
  • A.R. Saltiel

    Diverse signaling pathways in the cellular actions of insulin

    The American Journal of Physiology

    (1996)
  • R.T. Watson et al.

    Intracellular organization of insulin signaling and GLUT4 translocation

    Recent Progress in Hormone Research

    (2001)
  • T.P. Ciaraldi et al.

    Cellular mechanisms of insulin resistance in polycystic ovarian syndrome

    The Journal of Clinical Endocrinology and Metabolism

    (1992)
  • A. Dunaif et al.

    Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome

    Diabetes

    (1992)
  • A. Corbould et al.

    Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signalling

    American Journal of Physiology

    (2005)
  • A. Dunaif et al.

    Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)

    American Journal of Physiology

    (2001)
  • A. Dunaif et al.

    Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome

    The Journal of Clinical Investigation

    (1995)
  • C.B. Book et al.

    Selective insulin resistance in the polycystic ovary syndrome

    The Journal of Clinical Endocrinology and Metabolism

    (1999)
  • Cited by (0)

    Presented at the ‘12th International Congress on Hormonal Steroids and Hormones & Cancer’ (Athens, Greece, 13–16 September 2006).

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