Differential expression of epidermal growth factor receptor (EGF-R) gene and regulation of EGF-R bioactivity by progesterone and estrogen in the adult mouse uterus
- PMID: 7507841
- DOI: 10.1210/endo.134.2.7507841
Differential expression of epidermal growth factor receptor (EGF-R) gene and regulation of EGF-R bioactivity by progesterone and estrogen in the adult mouse uterus
Abstract
The present study examined several aspects of epidermal growth factor receptor (EGF-R) in the mouse uterus during the peri-implantation period and after ovarian hormone treatment of adult ovariectomized mice. The cell-specific distribution, regulation of expression, and binding kinetics were assessed by immunohistochemistry, Northern blot analysis, and ligand binding assays, respectively. Affinity cross-linking studies ascertained the size of the EGF-R, and its bioactivity was examined by determining EGF-dependent subcellular protein tyrosine kinase activity and receptor autophosphorylation. In the intact uterus and separated cell types, EGF-R was detected in the stroma, deciduum, and myometrium, but not in the luminal or glandular epithelium. Uterine EGF-R mRNA transcript profiles showed some differences between pregnant and ovariectomized mice regardless of steroid hormone treatments. Two major [6.5- and 2.7-kilobase (kb)] and two less abundant (9.6- and 5.0-kb) transcripts were detected in pregnant uterine poly(A)+ RNA. Three additional transcripts (< 2.0 kb) were detected in decidual poly(A)+ RNA, and a larger transcript (8.0 kb) was detected in uterine poly(A)+ RNA isolated from ovariectomized mice. Scatchard analysis of EGF binding also revealed apparent differences in binding kinetics between pregnant and ovariectomized mice, although EGF was cross-linked to a 170-kilodalton protein under these conditions. Two classes (Kd, approximately 0.2 and approximately 2.0 nM) of binding sites were noted in pregnant mice, whereas a single class (Kd, approximately 1.0 nM) was found in ovariectomized mice. 17 beta-Estradiol (E2) caused a rapid transient upregulation of uterine EGF-R mRNA levels and increased the number of EGF-binding sites in ovariectomized mice, as did an injection of progesterone (P4). However, the bioactivity of EGF-R could not be detected in uteri of ovariectomized mice treated with oil or P4. E2 treatment was found to be essential for EGF-R bioactivity. Taken together, the results suggest that in the adult mouse uterus, EGF-R status is influenced by factors other than P4 and E2, the epithelium is not the direct target for the actions of EGF-related growth factors as thought previously, the mitogenic effects of these growth factors on epithelial cells in vivo are perhaps mediated by other uterine cell-types expressing EGF-R, and, lastly, these growth factors are not likely to be functional in the uterus in the absence of estrogen. The present observations are supportive of the concept of paracrine or juxtacrine interactions between EGF-related growth factor ligands of luminal epithelial origin and blastocyst EGF-R in the process of implantation.
Similar articles
-
Differential regulation of heparin-binding epidermal growth factor-like growth factor in the adult ovariectomized mouse uterus by progesterone and estrogen.Endocrinology. 1994 Sep;135(3):1264-71. doi: 10.1210/endo.135.3.8070372. Endocrinology. 1994. PMID: 8070372
-
Expression of transforming growth factor-beta isoforms (beta 2 and beta 3) in the mouse uterus: analysis of the periimplantation period and effects of ovarian steroids.Endocrinology. 1992 Jun;130(6):3459-66. doi: 10.1210/endo.130.6.1375903. Endocrinology. 1992. PMID: 1375903
-
Differential expression of the erbB2 gene in the periimplantation mouse uterus: potential mediator of signaling by epidermal growth factor-like growth factors.Endocrinology. 1997 Mar;138(3):1328-37. doi: 10.1210/endo.138.3.4991. Endocrinology. 1997. PMID: 9048643
-
Expression of epidermal growth factor receptor (EGF-R), vascular endothelial growth factor receptor (VEGF-R) and fibroblast growth factor receptor (FGF-R) systems in porcine oviduct and endometrium during the time of implantation.J Reprod Dev. 2004 Jun;50(3):269-78. doi: 10.1262/jrd.50.269. J Reprod Dev. 2004. PMID: 15226591 Review.
-
Cross talk between peptide growth factor and estrogen receptor signaling systems.Environ Health Perspect. 1995 Oct;103 Suppl 7(Suppl 7):35-8. doi: 10.1289/ehp.95103s735. Environ Health Perspect. 1995. PMID: 8593872 Free PMC article. Review.
Cited by
-
Compensatory Estrogen Signal Is Capable of DNA Repair in Antiestrogen-Responsive Cancer Cells via Activating Mutations.J Oncol. 2020 Jul 28;2020:5418365. doi: 10.1155/2020/5418365. eCollection 2020. J Oncol. 2020. PMID: 32774370 Free PMC article. Review.
-
Expression of Insulin-Like Growth Factor 1 (IGF-1) and Epidermal Growth Factor (EGF) Receptors and the Effect of IGF-1 and EGF on Androgen and Estrogen Release in the Myometrium of Pigs-In Vitro Study.Animals (Basel). 2020 May 25;10(5):915. doi: 10.3390/ani10050915. Animals (Basel). 2020. PMID: 32466279 Free PMC article.
-
Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success.Nat Commun. 2018 Jun 22;9(1):2435. doi: 10.1038/s41467-018-04848-8. Nat Commun. 2018. PMID: 29934619 Free PMC article.
-
A Baboon (Papio anubis) simulated-pregnant model: cell specific expression of insulin-like growth factor binding protein-1 (IGFBP-1), type I IGF receptor (IGF-1 R) and retinol binding protein (RBP) in the uterus.Endocrine. 1995 Sep;3(9):639-51. doi: 10.1007/BF02746340. Endocrine. 1995. PMID: 21153222
-
Non-identical distribution pattern of epidermal growth factor and platelet-derived growth factor in the mouse uterus during the oestrous cycle and early pregnancy.Histochem J. 1998 Oct;30(10):711-22. doi: 10.1023/a:1003441904274. Histochem J. 1998. PMID: 9873998
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous