Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and lactation

Stanniocalcin is a glycoprotein hormone that appears to play a pancine/auto crine role in several mammalian tissues. Recently studies have shown that s tanniocalcin is highly expressed in the ovaries of mice and humans and we h ave investigated its expression in the mouse ovary during several physiolog ical states to identify potential functional relationships. During postnata l development the pattern of stanniocalcin (STC! gene expression begins to become thecalrestricted as early as day 5 and achieves the adult pattern of expression by two weeks of age. During postnatal development the primary s ites of STC protein localization are the theca and oocytes and after matura tion it is also strongly concentrated in the corpora lutea. Over the estrou s cycle the pattern of both STC gene expression and protein localization;lo not show dramatic changes though STC immunoreactivity (STCir) staining app ears to be greatest during metestrus I. In the superovulation model, howeve r, we observed a significant increase in STC messenger RNA (mRNA) levels af ter treatment with hCG implying regulation by LH. During gestation the expr ession of ovarian STC increases 15-fold and is localized to the theca-inter stitial cells with lower expression also being found in the corpora lutea. STC also becomes detectable in the serum for the first time suggesting an e ndocrine role for STC during gestation. Interestingly the presence of a nur sing litter appears to up-regulate STC gene expression in lactating mice su ggesting a role for ovarian STC in lactation. Also striking is the intense STCir staining found in oocytes as they are devoid of STC mRNA, thus implyi ng a role for STC in oocyte maturation. Stanniocalcin, to our knowledge, is unique because no other secreted proteins produced by the ovarian thecal-i nterstitial compartment are significantly induced during mouse pregnancy. I n summary, our data provide evidence for the active regulation of STC expre ssion in the ovary during gestation and lactation and therefore implies tha t STC is a new regulator of the gestational and nursing state.