[A study on the regulation of intrauterine milieu by bioactive substances of fetal origin in the human amniotic fluid--the analyses of interactions among amnion, chorion laeve, and decidua vera tissues].

To elucidate the regulatory mechanism of human intrauterine milieu, the effects of various substances on the production of endothelin (ET) and brain natriuretic peptide (BNP) by amnion cells were investigated. In addition, we examined the regulation of phospholipase D (PLD) activity, which has been shown to be involved in the signal transduction in various tissues such as ovary, adrenal gland, etc. The ET production by cultured amnion cells was stimulated by epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), or interleukin-1 (IL-1). Ligand binding analyses indicated that both ET-A receptor and ET-B receptor are present in chorion laeve, decidua vera, and myometrium, but not in the amnion tissue at term. However, amnion tissue in the second trimester showed a significant amount of binding capacity for ET-1 but not for ET-3, indicating the presence of ET-A receptor in this tissue in the second trimester. These observations were confirmed by Northern blot analyses. In cultured amnion cells, ET-B receptor was detected by Northern blot analysis. The expression of this ET-B receptor in cultured amnion cells was down-regulated by the addition of EGF, but not by ET-1, IL-1 or A23187. Moreover, ET-1 inhibited the secretion of prostaglandin E2 (PGE2) by cultured amnion cells. These results suggest that ET-1 secreted from amnion cells may block prostaglandin synthesis in amnion cells during the second trimester, but this block may be released at term by the action of EGF. The BNP production by cultured amnion cells was dose-dependently stimulated by TGF-beta, but was inhibited by cortisol or EGF. TGF-beta (approximately 400 pM) was detected in the human amniotic fluid by a bioassay. The TGF-beta augmented BNP production was blocked by the simultaneous treatment with cortisol or EGF. The receptor for BNP (particulate guanylate cyclase A-type: GC-A) was identified in chorion, decidua, and myometrium by both cGMP generation assay and Northern blot analysis. However, GC-A was not detected in amnion tissues in the second trimester and at term. In an in vitro experiment with rat pregnant uterus, both BNP and cGMP dose-dependently inhibited the prostaglandin F2 alpha induced uterine contraction. Thus, BNP secreted from amnion cells may not act on amnion tissue, but on the decidua and myometrium, and generate cGMP, the second messenger of BNP, and finally block uterine contraction during the second trimester.(ABSTRACT TRUNCATED AT 400 WORDS)