Immunization against growth hormone releasing factor or chronic feed restriction initiated at 3.5 months of age reduces ovarian response to pulsatile administration of gonadotropin-releasing hormone at 6 months of age and delays onset of puberty in heifers

A severe or moderate suppression of serum insulin-like growth factor I (IGF-I) was induced in heifers, beginning at 104 days of age, by active immunization against growth hormone-releasing factor (GRFi) or by chronic feed restriction (RES), respectively. We hypothesized that reduced serum IGE-I results in decreased serum estradiol-17 beta (E(2)), which in turn delays onset of puberty. The objectives of this experiment were to determine 1) whether GRFi and RES would alter follicular development and delay onset of puberty through similar mechanisms, and 2) whether GnRH would enhance follicular growth in control, GRFi, and RES heifers at 6 mo of age. Changes in IGF-I, somatotropin, LH, FSH, and E(2) were evaluated. Serum IGF-I was greater in control than in RES heifers, and was greater in both these groups than in GRFi heifers by 169 days of age. Basal LH decreased in control and RES but not in GRFi heifers from 136 to 157 days of age. During the same period, a decrease in mean FSH was detected in control but not in GRFi and RES heifers. RES decreased mean serum E(2) from 148 to 183 days of age. At 6 mo of age, pulsatile administration of GnRH (5 mu g every 2 h for 42-46 h) increased serum LH and FSH similarly across treatments but had no effect on the number of follicles less than or equal to 8 mm in GRFi and RES heifers relative to saline treatment. Serum E(2) and IGF-I in follicular fluid from follicles greater than or equal to 8 mm were increased in all GnRH-treated heifers; however, concentrations of both hormones were lower in GRFi than in control or RES heifers. The main effect of treatments on serum IGF-I was reflected in follicles less than or equal to 7 mm; follicular fluid IGF-I was greater in control than in RES heifers and was greater in both these groups than in GRFi heifers. Serum E(2) was lower in RES than in control and GRFi heifers from 253 to 281 days of age. Because of an interaction, E(2) was lower in GRFi-GnRH than in control-GnRH heifers but similar in GRFi-saline and control-saline heifers. By 393 days of age, 0% of RES and 32% of GRFi heifers had reached puberty compared to 71% of control heifers. These data support our hypothesis that decreased serum IGF-I results in decreased serum E(2). GRFi appears to delay puberty in heifers because decreased serum IGF-I impairs the ovary's ability to synthesize preovulatory concentrations of E(2), thereby delaying stimulation of an LH surge. In contrast, RES may delay puberty by delaying follicular development at two stages: a) decreased IGF-I in follicles less than or equal to 7 mm may delay predominant follicular growth, and b) decreased LH may delay maturation of the preovulatory follicle.