J. Huang et al., CELLULAR-LOCALIZATION AND HORMONAL-REGULATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN CYCLING MOUSE UTERUS, Journal of leukocyte biology, 57(1), 1995, pp. 27-35
Nitric oxide (NO), a potent and versatile free radical, is synthesized
in macrophages and mast cells as well as in other types of cells by t
he inducible form of nitric oxide synthase (iNOS). In this study, cell
s containing iNOS were identified in the uteri of cycling mice by usin
g a rabbit antibody generated to an iNOS-specific peptide. Macrophages
were identified in semiserial sections of the same tissues with the m
onoclonal antibody, F4/80, and mast cells were identified by toluidine
blue staining. In tissue sections of uteri obtained from mice in the
four stages of the estrous cycle (8 to 11 mice per stage), iNOS immuno
reactivity was strongest in diestrus-I uteri and weakest in diestrus-I
I uteri. Myometrial mast cells and endometrial epithelial cells were p
rominent locations of iNOS, and specific protein was also present in m
yometrial smooth muscle and macrophage-like cells in the endometrial s
troma. Because cyclic variations suggested regulation of iNOS expressi
on by ovarian steroid hormones, studies were done using ovariectomized
mice. Seven days after ovariectomy, immunoreactive iNOS was low but d
etectable in mast cells and luminal epithelial cells. In the uteri of
ovariectomized, estradiol-17 beta (E(2))-treated mice, mast cells were
iNOS(+) after 24 h whereas epithelial cells were negative; the revers
e was observed in progesterone (P-4)-treated mice. Both mast cells and
epithelial cells were iNOS(+) in the uteri of mice that had received
a combination of E(2) + P-4. These results indicate that several types
of uterine cells produce iNOS and that expression of this enzyme in s
pecific cell lineages is governed by ovarian steroid hormones. The dat
a are consistent with the postulate that NO derived from uterine leuko
cytes and other types of cells plays a role in uterine cyclicity and p
reparation for pregnancy.