Bj. Waddell et Pj. Burton, Full induction of rat myometrial 11 beta-hydroxysteroid dehydrogenase type1 in late pregnancy is dependent on intrauterine occupancy, BIOL REPROD, 62(4), 2000, pp. 1005-1009
The 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1) enzyme cata
lyses the conversion of the biologically inert glucocorticoid 11-dehydrocor
ticosterone to active corticosterone (11-oxoreductase activity) in vivo, an
d it is dramatically up-regulated in uterine myometrium in the days leading
up to parturition. 11 beta-HSD-1 is likely to enhance local concentrations
of glucocorticoid within the myometrium and thus facilitate uterine contra
ctility, but the stimulus for the increase in myometrial 11 beta-HSD-1 is u
nknown. The objective of the present study was to test whether the inductio
n of myometrial 11 beta-HSD-1 is dependent on uterine occupancy or systemic
hormonal signals of exposed to the normal systemic hormonal milieu of preg
nancy. Western blot analysis showed that the 11 beta-HSD-1 signal was only
partially induced in the nongravid horn of ULP rats on Day 22 of pregnancy
(term: Day 23). Moreover, artificial distension of this nongravid horn had
no effect on myometrial 11 beta-HSD-1 immunoreactivity or bioactivity at ei
ther Day 16 or Day 22 of pregnancy. Removal of fetuses and placentas on Day
18 reduced myometrial 11 beta-HSD-1 bioactivity 4 days later, and this eff
ect was not overcome by artificial maintenance of uterine distension. In co
ntrast, after fetectomy at Day 18 (i.e., removal of the fetus but not place
nta), myometrial 11 beta-HSD-1 bioactivity was largely maintained on Day 22
, indicative of placental support for myometrial 11 beta-HSD-1 over this pe
riod.
In conclusion, our data show that full induction of myometrial 11 beta-HSD-
1 expression and associated 11-oxoreductase bioactivity late in rat pregnan
cy is dependent upon intrauterine occupancy. Although the hormonal milieu o
f late pregnancy appears to stimulate myometrial 11 beta-HSD-1 marginally,
full induction clearly requires an additional stimulus. Manipulations invol
ving fetectomy and artificial uterine distension indicate that the placenta
provides at least part of this stimulus, but uterine stretch does not appe
ar to play a role.