The Kiss1 system and polycystic ovary syndrome lessons from physiology and putative pathophysiologic implications

Capsule:
Potential implications of alterations of the Kiss1 system in the pathophysiology of polycystic ovary syndrome are discussed. The limited experimental and clinical evidence supporting such a role is summarized.

Authors:
Selma F. Witchel, M.D., Manuel Tena-Sempere, M.D., Ph.D.

Volume 100, Issue 1, Pages 12-22, July 2013

Abstract:

Polycystic ovary syndrome (PCOS) is a highly prevalent heterogeneous disease characterized by ovulatory dysfunction, hyperandrogenism, and metabolic alterations. Women with PCOS commonly display dysregulated gonadotropin secretion with higher LH pulsatility and perturbed LH-FSH ratios, which likely contributes to the ovarian phenotype and might be indicative of disrupted GnRH secretory activity. Although the involvement of altered androgen and insulin levels in the pathogenesis of the neuroendocrine alterations of PCOS has been explored in various experimental and clinical settings, the ultimate mechanisms whereby such neurohormonal perturbations take place remain partially unknown. In recent years, kisspeptins, the products of the Kiss1 gene that operate via the surface receptor Gpr54, have emerged as essential elements of the reproductive brain that play an indispensable role in the control of gonadotropin secretion and ovulation. In addition, Kiss1 neurons in the brain are targets and transmitters of the regulatory actions of sex steroids and metabolic cues on the reproductive axis during early organizing periods and adulthood. Furthermore, Kiss1/kisspeptin expression has been documented in the ovary in various species, including humans; yet clear evidence for the involvement of kisspeptin signaling in the control of ovulation, or its alterations, is still pending. Based on these physiologic features, we discuss the putative pathophysiologic implications of alterations of the Kiss1 system in the generation of PCOS and summarize the scarce experimental and clinical evidence that might support such a role.

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