Hormonal Regulation of Insulin-Like Growth Factor Gene Expression in Pig Uterus*

The present studies were undertaken to define potential regulation of endometrial insulin-like growth factor-I (IGF-I) synthesis and secretion by steroid hormones and to correlate conceptus- and serum-derived estrogens with these events. Four experimental groups of gilts were studied: 1) prepubertal gilts administered estradiol (E) and/or progesterone (P4) daily for up to 15 days; 2) mature gilts ovariectomized (ovx) on day 2 of the estrous cycle, and then administered E, P4, or E plus P4 from days 4-11 after estrus; 3) unilaterally pregnant gilts on day 12 or 16 after the onset of estrus; and 4) cyclic gilts administered E on day 11 and hysterectomized 1, 6, 12, or 24 h after E. IGF-I mRNA was measured by blot hybridization of total cellular RNAs, while a specific RIA was used to quantitate levels of tissue and uterine luminal fluid (ULF) IGF-I. In prepubertal gilts, E or P4 increased uterine IGF-I mRNA levels and IGF-I protein. Mature, ovx gilts treated with E, P4, or E plus P4 had increased levels of endometrial IGF-I mRNAs and protein and luminal IGF-I. The magnitude of E or P4 induction was comparable and was not additive. Gravid horns on day 12 had higher amounts of IGF-I in ULF compared to day 12 nongravid horns or day 16 gravid and nongravid horns. However, no significant differences in the amounts of endometrial IGF-I mRNA and tissue IGF-I content between horns on each day were detected. Acute treatment of cyclic gilts (day 11) with E increased levels of endometrial IGF-I mRNAs and luminal IGF-I 1 h after treatment. The effect of E was transient and was reversed within 24 h of E injection. IGF-II and IGF-binding protein-2 mRNAs were regulated by E and P4 distinct from IGF-I mRNAs. These results indicate that E and P4 are involved in the normal regulation of uterine IGF-I synthesis and/or secretion. However, the relative contributions of serum and conceptus-derived estrogens in these processes during the preimplantation period in the pig remain to be defined.