Insulin-Like Growth Factors and Ovarian Follicular Development*

INSULIN-like growth factor-I (IGF-I) and its structural homologue, IGF-II, are low molecular weight peptides that promote cellular mitosis and differentiation in a variety of systems and are believed to play a role in cyclic ovarian follicular development. In 1978, IGF-I and IGF-II were purified and sequenced by Rinderkneckt and Humbel (1, 2), and since that time there has been an exponential accumulation of information regarding these peptides, as well as their receptors, and their binding proteins (IGFBPs), constituents of the “IGF autocrine/paracrine system.” These constituents have been examined in various tissues in vivo under a variety of physiological conditions and in vitro in numerous cell and tissue culture systems in several species (for review see Refs. 3–9). A decade ago, research on the IGFs focused on skeletal growth in childhood, a subspecialty of pediatric endocrinology. In the intervening years, the arena of research inquiry extended to other disciplines, including nephrology, ophthalmology, adult endocrinology, surgery, genetics, and reproductive endocrinology. Adashi and colleagues (10) published in 1985, in this journal, an elegant and comprehensive monograph describing what was known at that time about the IGFs and their roles as intraovarian regulators of granulosa cell growth and function. New information on the IGF system in the ovary has been accumulating rapidly during the years since Adashi's review, mainly due to two major advances in science and medicine. First, advances in molecular biology have provided details of the structures of the IGFs, IGFBPs, and IGF receptors. Complementary and genomic DNA for most of the components of the IGF system have been cloned and sequenced (reviewed in Refs. 3–9), opening the way for understanding regulation and function of these peptides and proteins in the ovary, as well as in other tissues. Second, the clinical practice of reproductive endocrinology has been revolutionized by the advent of in vitro fertilization and embryo transfer (IVF-ET) as treatment for infertility due to a variety of causes. Follicular growth, in response to exogenous gonadotropin administration, can be observed by ultrasound, and human granulosa cells, components of follicular aspirates during oocyte retrieval for IVF-ET, have become plentiful for examination in the laboratory. In addition, the repertoire of agents used for ovulation induction for IVF-ET has increased, and GH, the main regulator of serum IGF-I levels, has been included as an adjunct to gonadotropins in some ovulation induction protocols. Along with studies on human follicular constituents and granulosa cells obtained from follicles exposed to a variety of ovulation induction agents, continued basic research in animal models has brought comparative physiology of normal and abnormal ovarian function into a new age of investigation.