Female Reproductive Tract

Estrogen Induces Expression of Secretory Leukocyte Protease Inhibitor in Rat Uterus

Abstract
In rodents, the steroid hormone estrogen (E) profoundly influences the early events in the uterus leading to embryo implantation. It is thought that E triggers the expression of a unique set of genes in the endometrium that in turn control implantation. To identify these E-induced genes, we employed a delayed implantation model system in which embryo attachment to rat endometrium is dependent upon E administration. Using a gene expression screen method, we isolated a number of cDNAs representing mRNAs whose expression is either turned on or turned off in response to an implantation-inducing dose of E. We identified one of these cDNAs as that encoding secretory leukocyte protease inhibitor (SLPI), an inhibitor of serine proteases. The expression of SLPI mRNA was induced in the uteri of ovariectomized rats in response to E, confirming the hormonal regulation of this molecule. Spatio-temporal analysis revealed a bi-phasic pattern of expression of SLPI mRNA during early pregnancy. A considerable amount of SLPI mRNA was detected in the uterine epithelium on day 1 of pregnancy. The level of this mRNA, however, declined sharply on days 2-3 of gestation. Interestingly, on day 4 of gestation, there was a marked resurgence in SLPI mRNA expression in the uterine epithelium. This second burst of SLPI expression diminished by day 6 of pregnancy. The transient induction of SLPI mRNA during days 4-5 overlapped with the window of implantation in the rat. Although the precise function of SLPI in the uterus eludes us presently, its known effects as a serine protease inhibitor in other tissues and its hormone-induced expression in the rat uterus immediately preceding implantation lead us to propose that this gene plays an important role in controlling excessive proteolysis and inflammation during a critical phase of early pregnancy.

Key words: Female Reproductive Tract • Estradiol receptor • Implantation • Uterus

This article has been cited by other articles:

				K. Don Yi and J. W. Simpkins Protein Phosphatase 1, Protein Phosphatase 2A, and Calcineurin Play a Role in Estrogen-Mediated Neuroprotection Endocrinology, October 1, 2008; 149(10): 5235 - 5243. [Abstract] [Full Text] [PDF]

				M.H. Hassan, N. Khatoon, D.T. Curiel, F.M. Hamada, H.M. Arafa, and A. Al-Hendy Toward gene therapy of uterine fibroids: targeting modified adenovirus to human leiomyoma cells Hum. Reprod., March 1, 2008; 23(3): 514 - 524. [Abstract] [Full Text] [PDF]

				R. Moral, R. Wang, I. H Russo, C. A Lamartiniere, J. Pereira, and J. Russo Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature J. Endocrinol., January 1, 2008; 196(1): 101 - 112. [Abstract] [Full Text] [PDF]

				J. V. Fahey, T. M. Schaefer, and C. R. Wira Sex hormone modulation of human uterine epithelial cell immune responses Integr. Comp. Biol., December 1, 2006; 46(6): 1082 - 1087. [Abstract] [Full Text] [PDF]