Histidine decarboxylase gene in the mouse uterus is regulated by progesterone and correlates with uterine differentiation for blastocyst implantation

Cell-cell interactions between the blastocyst trophectoderm and uterine luminal epithelium are essential to the process of implantation. The factors that participate in these interactions or their mechanism of actions are poorly understood. Histamine has long been suspected as one of the factors that is involved in implantation. Histamine is formed from L-histidine by histidine decarboxylase (HDC). We examined the expression and regulation of HDC gene in the mouse uterus during early pregnancy and under steroid hormonal stimulation. Northern blot hybridization detected a 2.6-kb transcript of HDC messenger RNA (mRNA) in uterine poly(A)(+) RNA samples. Maximum uterine accumulation of HDC mRNA occurred on days 3 and 4 of pregnancy, followed by marked declines on later days (days 5-8). In ovariectomized mice, uterine mRNA levels were up-regulated by an injection of progesterone (P-4) by 6 h, and the levels were maintained through 24 h. In contrast, an injection of estradiol-17 beta neither stimulated nor antagonized P-4-induced WDC mRNA accumulation. P-4-induced up-regulation was considerably abrogated by pretreatment with RU-486, a P-4 receptor antagonist, suggesting involvement of P-4 receptor. In situ hybridization detected HDC mRNA specifically in uterine epithelial cells but not in other cell types. Again, high epithelial accumulation occurred on day 4 of pregnancy. With the progression of implantation (days 5-8), HDC mRNA levels declined in the luminal epithelium surrounding the implanting blastocysts, as compared with that away from the blastocysts. Immunoreactive histamine and HDC were colocalized with HDC mRNA. Western blotting detected a 54-kDa protein in epithelial cell extracts, which also exhibited HDC activity. Expression of HDC in epithelial cells, preceding implantation on day 4, at lower levels after initiation of implantation on day 5, and its regulation by P-4 suggest that this gene plays an important role in implantation.