INSULIN‐LIKE GROWTH FACTOR‐I (IGF‐I) AND IGF‐I BINDING PROTEIN IN THE FOLLICULAR FLUIDS OF GROWTH HORMONE TREATED PATIENTS

Abstract

The presence of GH, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), oestradiol (E2) and progesterone (PG) were investigated in the fluids obtained from various ovarian follicles of seven patients in whom the induction of super-ovulation was achieved only after GH (0.1 U/kg BW/day) was added to the gonadotrophin therapy. The follicular fluids of six patients responsive to treatment with gonadotrophin alone served as a control. In patients treated with combined therapy, the results demonstrated the presence in the follicular fluids of GH (M .+-. SEM: 8.5 .+-. 0.6 mU/l), E2 (771 .+-. 38 nmol/l), and PG (16.4 .+-. 0.7 pmol/l) in significantly higher concentrations compared to that in control follicles (6.2 .+-. 0.8 mU/l, 681 .+-. 30 nmol/l, and 14.4 .+-. 0.6 pmol/l; P = 0.002, 0.012, 0.0001 respectively). Acid-extractable IGF-I (143 .+-. 9 ng/ml) and EGF (3.9 .+-. 0.3 ng/ml) concentrations were similar to those of control fluids (124 .+-. 10 ng/ml and 2.9 .+-. 0.7 ng/ml respectively) and were highly correlated with each other (P < 0.001), suggesting a stimulatory effect of EGF on the local IGF-I production. A correlation between GH and IGF-I (n = 51, r = 0.36), as well as between IGF-I and PG (n = 48, r = 0.77) and E2 (n = 48, r = 0.55) was evident only in the follicular fluid of GH-treated subjects. In patients with gonadotrophin-resistant anovulation the significant correlation (P < 0.01) between GH and IGF-I suggests that GH administration influences the IGF-I local concentration, and therefore, as IGF-I becomes correlated with PG (P < 0.001) and E2 (P < 0.001), it promotes the growth and maturation of the follicles. In the same patients, no correlation was evident between LH and IGF-I, E2 and PG, while a significant correlation was present between FSH and IGF-I as well as with PG (P < 0.001). The IGF-I binding protein (BP) assay also demonstrated the presence of a considerable amount of IGF-I binding sites in all fluids. The characterization of these IGF-I binding sites demonstrated an IGF-I-BP complex of 35 kDa, similar to that found in the amniotic fluid and to the placental protein 12. These data support a role for GH and IGF-I in the control of follicular growth and development in humans. This also supports the hypothesis of a proliferative and/or permissive effect of IGF-I in ovarian tissue.