Insulin-Like Growth Factor-I (IGF-I) in Reproductive System of Female - A Review

IGF-I in Female Reproductive System

  • Hasbi Hasbi Department of Animal Production, Faculty of Animal Science, Hasanuddin University Jalan Perintis Kemerdekaan Km. 10, Makassar 90245, Indonesia
  • Sri Gustina Department of Animal Husbandry, Faculty of Animal husbandry and Fisheries, Universitas Sulawesi Barat, Jl. Prof. Dr. Baharuddin Lopa, Tande Timur, Majene, 91412, Indonesia
Keywords: Insulin-like Growth Factor–I, endocrine, paracrine, autocrine, female reproductive system


Insulin-like Growth Factor-I is a peptide with a molecular weight of 7649 Da. The IGF system is a complex molecule that can act autocrine, paracrine and endocrine which can be produced in the uterus, oviduct, ovaries, hypothalamus, and liver. Basically, IGF consists of six IGF-binding proteins (IGFBP 1 to 6) and two growth factors are IGF-I and IGF-II, two cell surface receptors (IGF-IR and IGF mannose-6-phosphate receptor (M-6-PR)) and nine related IGFBP proteins (IGFBP-rPS). IGFs are involved in cell proliferation, growth, differentiation and survival of cells as well as in metabolic regulation protein, glucose, and fat. Unlike insulin, the circulation of IGFs in complex plasma with a group of IGF specific binding proteins (IGFBPs). In the circulatory system more than 99% of IGFs are bound and means less than 1% in free. IGF-I plays a role in the female reproductive system, especially in the ovaries to stimulate development and growth of follicles (preantral follicles to antral follicles), stimulate the onset of puberty, maintain estrous cycles until can get pregnant, and during the postpartum period.


Z. Laron. “Insulin like growth factor I (IGF-I): a growth hormon”. J Clinical Pathol, vol. 54, pp. 311-316, 2001.

R. Gill, C. Verma, B. Wallach, B. Urso, J. Pitts, Awollmer, P. De Meyts and M. Wood. “Modeling of the disulphide swapped isomer of human insulin like growth factor I: Implication for receptor binding”. Oxford J Prot Eng, vol. 12, pp. 297-303, 1999.

M. P. Brugts. IGF-I Bioactivity in Aging, Health and Disease [Thesis]. Netherlands (NL): Erasmus Universiteit Rotterdam, 2009.

M. A. Velazquez, L. J. Spicer and D. C. Wathes. “The role of endocrine insulin-like growth factor-I (IGF-I) in female bovine reproduction”. Domestic Anim Endocrinol, vol. 35, pp. 325–42, 2008.

J. A. Janssen and S. W. Lamberts SW. “The role of IGF-I in the development of cardiovascular disease in type 2 diabetes mellitus: is prevention possible?”. Eur J Endocrinol, vol. 146, pp. 467-77, 2002.

M. D. Sadick, A. Intintoli, V. Quarmby, A. McCoy, E. Canova-Davis and V. Ling. “Kinase receptor activation (KIRA): a rapid and accurate alternative to end-point bioassays”. J Pharm Biomed Anal, vol. 19, pp. 883-91, 1999.

E. Conti, C. Carrozza, E. Capoluongo, M. Volpe, F. Crea, C. Zuppi and F. Andreotti F. “Insulin like growth factor-1 as a vascular protective factor”. Circulation, vol. 110, pp. 2260-65, 2004.

D. J. Schaid, C. M. Rowland, D. E. Tines, R. M. Jacobson and G. A. Poland. “Score tests for association between traits and haplotypes when linkage phase is ambiguous”. Am J Hum Genet, vol. 70, pp. 425-34, 2002.

R. J. Scaramuzzi, J. F. Murray, J. A. Downing and B. K. Campbell. “The effects of exogenous growth hormone on follicular steroid secretion and ovulation rate in sheep”. Domest Anim Endocrinol, vol. 17, pp. 269–77, 1999.

J. E. Kinder, E. G. Bergfeld, M. E. Wehrman, K. E. Peters and F. N. Kojima. “Endocrine basis for puberty in heifers and ewes”. J Reprod Fertil, vol. 49(Suppl.), pp. 393–407, 1995.

N. C. Rawlings, A. C. O. Evans, A. Honaramooz and P. M. Bartlewski. “Antral follicle growth and endocrine changes in prepubertal cattle, sheep and goats”. Anim Reprod Sci, vol. 78, pp. 259–70, 2003.

L. J. Spicer, I. Bossis and R. P. Wettemann. “Effect of plasma from cyclic versus nutritionally induced anovulatory beef heifers on proliferation of granulosa cells in vitro”. Domest Anim Endocrinol, vol. 34, pp. 250–53, 2008.

T. M. Prado, R. P. Wetteman, L. J. Spicer, J. A. Vizcarra and G. L. Morgan GL. “Influence of exogenous gonadotropin-releasing hormone on ovarian function in beef cows after short- and long-term nutritionally induced anovulation”. J Anim Sci, vol. 80, pp. 3268–76, 2002.

C. M. Perks, A. R. Peters and D. C. Wathes. “Follicular and luteal expression of insulin-like growth factors I and II and the type 1 IGF receptor in the bovine ovary”. J Reprod Fertil, vol. 116, pp. 157–65, 1999.

D. Schams, B. Berisha, M. Kosmann, R. Einspanier and W. M. Amselgruber. “Possible role of growth hormone, IGFs, and IGF-binding proteins in the regulation of ovarian function in large farm animals”. Domest Anim Endocrinol, vol. 17, pp. 279–85, 1999.

M. J. Vandehaar, B. K. Sharma and R. L. Fogwell. “Effect of dietary energy restriction on the expression of insulin-like growth factor-I in liver and corpus luteum of heifers”. J Dairy Sci, vol. 78, pp. 832–41, 1995.

M. C. Yung, M. J. Vandehaar, R. L. Fogwell and B. K. Sharma. “Effect of energy balance and somatotropin on insulin-like growth factor I in serum and on weight and progesterone of corpus luteum in heifers”. J Anim Sci, vol. 74, pp. 2239–44, 1996.

D. K. Bishop, R. P. Wettemann and L. J. Spicer. “Body energy reserves influence the onset of luteal activity after early weaning in beef cows”. J Anim Sci, vol. 72, pp. 2703–8, 1994.

K. Vendola, J. Zhou, J. Wang, O. A. Famuyiwa, M. Bievre and C. A. Bondy. “Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary”. Biol Reprod, vol. 61, pp. 353–57, 1999.

J. E. Fortune, G. M. Rivera and M. Y. Yang. “Follicular development: the role of the follicular microenvironment in selection of the dominant follicle”. Anim Reprod Sci, vol. 83, pp. 109–26, 2004.

D. G. Armstrong, G. Baxter, C. O. Hogg and K. J. Woad. “Insulin-like growth factor (IGF) system in the oocyte and somatic cells of bovine preantral follicles”. Reproduction, vol. 123, pp. 789–97, 2002.

J. R. V. Silva, J. R. Figueiredo and R. Van den Hurk. “Involvement of growth hormone (GH) and insulin-like growth factor (IGF) system in ovarian folliculogenesis”. Theriogenology, vol. 71, pp. 1193–1208, 2009.

I. Demeestere, C. Gervy, J. Centner, F. Devreker, Y. Englert and A. Delbaere. “Effect of insulin-like growth factor-I during preantral follicular culture on steroidogenesis, in vitro oocyte maturation, and embryo development in mice”. Biol Reprod, vol. 70, pp. 1664–9, 2004.

P. M. Hastie and W. Haresign. “Expression of mRNAs encoding insulin-like growth factor (IGF) ligands, IGF receptors and IGF binding proteins during follicular growth and atresia in the ovine ovary throughout the oestrous cycle”. Anim Reprod Sci, vol. 92, pp. 284–99, 2006.

P. L. Senger. Pathways to pregnancy and parturition. 2nd ed. Washington (US): Current Conceptions, Inc. pp. 174, 2005.

E. Knobil and J. D. Neill’s. Fisiologi of Reproduction. 3th ed. New York (US): Academic Press. pp. 532, 2006.

G. E. Mann, M. D. Fray and G. E. Lamming. “Effects of time of progesterone supplementation on embryo development and interferon-τ production in the cow”. Vet J, vol. 171, pp. 500–3, 2006.

K. L. Hossner, M. D. Holland, S. E. Williams, C. R. Wallace, G. D. Niswender and K. G. Odde. “Serum concentrations of insulin-like growth factors and placental lactogen during gestation in cattle. II. Maternal profiles”. Domest Anim Endocrinol, vol. 14, pp. 316–24, 1997.

M. G. Diskin, D. R. Mackey, J. F. Roche and J. M. Sreenan. “Effects of nutrition and metabolic status on circulating hormones and ovarian follicle development in cattle”. Anim Reprod Sci, vol. 78, pp. 345–70, 2003.

V. C. Zulu, T. Nakao and Y. Sawamukai. “Insulin-like growth factor-I as a possible hormonal mediator of nutritional regulation of reproduction in cattle”. J Vet Med Sci, vol. 64, pp. 657–65, 2002.

L. M. Rutter, R. Snopek and J. G. Manns. “Serum concentrations of IGF-1 in postpartum beef cows”. J Anim Sci, vol. 67, pp. 2060–6, 1989.