Characterization, localization, and regulation of receptors for insulin-like growth factor I in the baboon uterus during the cycle and pregnancy.

Abstract

The objective of this study was to determine the presence, regulation, and localization of specific receptors for insulin-like growth factor I (IGF-I) in primate reproductive tissues. Uteri were obtained from baboons either during the menstrual cycle, after ovariectomy with or without steroid treatments, or during early pregnancy (Days 18-60 postovulation [PO]). Placental and decidual tissues were collected from baboons during late pregnancy (Days 130-160). Localization of type I IGF receptor was determined by indirect immunocytochemistry (alpha IR3 antibody), and levels of type I IGF receptors were determined by affinity cross-linking and binding assays. Specific staining for type I IGF receptors was present in the membranes of glandular epithelial cells throughout the cycle and early pregnancy; however, there was a decrease in staining intensity by the late luteal phase and also throughout early pregnancy compared to the late follicular phase. Specific receptor staining was absent in stromal cells throughout the cycle. By Day 19 PO, stromal cells directly under the trophoblast were positive for type I IGF receptor, and an increase in stromal staining at the implantation site was observed as pregnancy proceeded. Stromal staining was apparent in non-implantation site tissue by Day 32 PO. Some placental villi showed positive receptor staining as early as on Day 18 PO, and an increase in the number of positive villi was apparent as pregnancy progressed. An 125I-IGF-I-protein complex of approximately 140,000 daltons, corresponding to the alpha subunit of the type I IGF receptor, was detected in endometrial, placental, and decidual membranes. The intensity of this signal was high in endometrium from the follicular phase, whereas low levels were detected in endometrium from the luteal phase. Throughout early pregnancy, alpha receptor subunit was present in placental and decidual membranes; alpha receptor subunit increased in placenta as pregnancy proceeded. An additional 125I-IGF-I-protein complex of 43,000 daltons, corresponding to IGF binding protein-1 (IGFBP-1), was present in decidual membranes and appeared to increase as pregnancy proceeded. Specific binding of 125I-IGF-I to placental membranes was displaced by unlabeled IGF-I and alpha IR3 antibody, whereas both unlabeled IGF-I and IGF-II competed equally for binding to decidual membranes. Scatchard analysis of 125I-IGF-I binding to placental membranes revealed a single class of high-affinity receptors (KD = 2.35 +/- 0.8 nM; mean +/- SEM).(ABSTRACT TRUNCATED AT 400 WORDS)