NEONATAL AGE AND PERIOD OF ESTROGEN EXPOSURE AFFECT PORCINE UTERINE GROWTH, MORPHOGENESIS, AND PROTEIN-SYNTHESIS

To determine whether neonatal age and estrogen exposure affect uterine growth, morphogenesis, and protein synthesis, crossbred gilts were ra ndomly assigned at birth (Day 0) to receive cipher com oil vehicle (CO ) or estradiol-17beta valerate (EV; 50 mug/kg BW/day). Gilts were trea ted for 7 days, chosen to coincide with specific periods of uterine de velopment, prior to hysterectomy on Day 7, 14, or 49. Uteri were weigh ed, and tissues were fixed for histology or explanted with L-4,5-[H-3] leucine (H-3-leu) for 24 h. Endometrial and myometrial thicknesses wer e measured in uterine wall cross sections. Radiolabeled proteins produ ced by uterine wall tissues from H-3-leu and released into explant med ium were identified by fluorography of two-dimensional SDS-PAGE gels. Proteins for which fluorographic spot intensities were consistently af fected by age and/or treatment were excised from gels, and associated radioactivity was quantified. Normal growth and histogenesis were obse rved in uteri from CO-treated gilts. Exposure to EV increased (p < 0.0 1) uterine wet weight on all days examined, although effects were most pronounced on Day 49 (day X treatment, p < 0.01). Histologically, ute ri of EV-treated gilts exhibited precocious or altered patterns of dev elopment of endometrial glands and folds. Endometrial thickness was gr eater (p < 0.01) in EV-treated gilts, and response was most pronounced on Day 49 (day x treatment, p < 0.01). Treatment with EV increased (p < 0.01) myometrial thickness on Day 49 only. Twenty-five uterine prot eins were identified to be affected consistently by neonatal age, EV, or both. Production of four of these proteins was affected by age alon e, while six were affected exclusively by treatment with EV alone, and 15 were affected differentially by both age and EV. Treatment with EV affected production of three of these 25 proteins on Day 7, 8 of 25 o n Day 14, and 14 of 25 on Day 49. Results indicate that uterine growth and development of the porcine uterine wall during early neonatal lif e are accompanied by predictable alterations in patterns of uterine pr otein synthesis. Data also demonstrate that the neonatal porcine uteru s is estrogen-sensitive and that both physical and biochemical respons es of uterine tissues to estrogen vary with period of exposure. It is suggested that EV may be useful as a tool with which to induce develop mental lesions in neonatal porcine uterine tissues. Identification of EV-induced lesions in adult uterine tissues and of the neonatal period s associated with their induction will represent an important step tow ard identification of developmental determinants of porcine uterine ca pacity.