Creatine kinase isoenzymes are highly regulated during pregnancy in rat uterus and placenta

Creatine kinase (CK) isoenzymes play a central role in energy transfer. Expression of CK isoenzymes in rat uterus and placenta was analyzed to evaluate their contribution to energy metabolism during pregnancy and delivery. Tissue from the uterine horns and placentas of pregnant rats from day 14 of gestation to 17 days postpartum was analyzed for expression of "brain" CK (BCK) and ubiquitous mitochondrial CK (uMtCK) mRNA, protein, and enzyme activity. uMtCK mRNA expression is high in prepartum uterus, but rapidly falls (> 10-fold) after delivery to a nadir at 7 days postpartum. Prepartum BCK mRNA expression is coordinate with uMtCK but has a 15-fold greater expression than uMtCK. Both CK mRNAs rise by 17 days postpartum. Both BCK and uMtCK mRNA expressions are strongly induced in placenta at 20 days gestation with a rapid fall (> 6-fold) immediately before delivery. Protein expression of BCK and uMtCK is also coordinate. However, analysis of mRNA and protein expression indicates that significant posttranscriptional regulation of both kinds of CK also occurs. CK activity in uterus and placenta reflects BCK expression. By immunohistochemistry, BCK and uMtCK protein expression is highly localized in the placenta and endometrium of prepartum uterus. This expression shifts entirely to the uterine smooth muscle by 17 days postpartum. uMtCK mRNA expression is rapidly induced by beta-estradiol in vitro (> 6-fold), demonstrating estrogen-responsive elements in the uMtCK nuclear gene. Thus a second isoenzyme of CK, uMtCK, is expressed in rat uterus and placenta and is highly regulated with BCK. These results suggest an important role for CK in the maintenance and termination of pregnancy.