Excess of nerve growth factor in the ovary causes a polycystic ovary-like syndrome in mice, which closely resembles both reproductive and metabolic aspects of the human syndrome

Jenny L. Wilson, Weiyi Chen, Gregory A. Dissen, Sergio R. Ojeda, Michael A. Cowley, Cecilia Garcia-Rudaz, Pablo J. Enriori

    Research output: Contribution to journalArticle

    10 Scopus citations

    Abstract

    Polycystic ovarian syndrome (PCOS), the most common female endocrine disorder of unknown etiology, is characterized by reproductive abnormalities and associated metabolic conditions comprising insulin resistance, type 2 diabetes mellitus, and dyslipidemia. We previously reported that transgenic overexpression of nerve growth factor (NGF), a marker of sympathetic hyperactivity, directed to the ovary by the mouse 17α-hydroxylase/C17-20 lyase promoter (17NF mice), results in ovarian abnormalities similar to those seen in PCOS women. To investigate whether ovarian overproduction of NGF also induces common metabolic alterations of PCOS, we assessed glucose homeostasis by glucose tolerance test, plasma insulin levels, and body composition by dual-energy x-ray absorptiometry scan in young female 17NF mice and wild-type mice. 17NF mice exhibited increased body weight and alterations in body fat distribution with a greater accumulation of visceral fat compared with sc fat (P < .01). 17NF mice also displayed glucose intolerance (P < .01), decreased insulin-mediated glucose disposal (P < .01), and hyperinsulinemia (P < .05), which, similar to PCOS patients, occurred independently of body weight. Additionally, 17NF mice exhibited increased sympathetic outflow observed as increased interscapular brown adipose tissue temperature. This change was evident during the dark period (7 PM to 7 AM) and occurred concomitant with increased interscapular brown adipose tissue uncoupling protein 1 expression. These findings suggest that overexpression of NGF in the ovary may suffice to cause both reproductive and metabolic alterations characteristic of PCOS and support the hypothesis that sympathetic hyperactivity may contribute to the development and/or progression of PCOS.

    Original languageEnglish (US)
    Pages (from-to)4494-4506
    Number of pages13
    JournalEndocrinology
    Volume155
    Issue number11
    DOIs
    StatePublished - Nov 1 2014

    ASJC Scopus subject areas

    • Endocrinology

    Fingerprint Dive into the research topics of 'Excess of nerve growth factor in the ovary causes a polycystic ovary-like syndrome in mice, which closely resembles both reproductive and metabolic aspects of the human syndrome'. Together they form a unique fingerprint.

  • Cite this