Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries

J Clin Endocrinol Metab. 2013 Aug;98(8):3298-305. doi: 10.1210/jc.2013-1378. Epub 2013 Jun 7.

Abstract

Context: Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development.

Objective: Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries.

Design: We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture.

Setting: This was a laboratory-based study, using clinical tissue samples.

Patients: A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography.

Main outcome measures: We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries.

Results: IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture.

Conclusions: IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Middle Aged
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / growth & development*
  • Polycystic Ovary Syndrome / physiopathology*
  • RNA, Messenger / analysis
  • Receptor, IGF Type 1 / analysis
  • Receptor, IGF Type 1 / genetics
  • Somatomedins / physiology*

Substances

  • RNA, Messenger
  • Somatomedins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1