Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and lactation

Stanniocalcin is a glycoprotein hormone that appears to play a pancine/autocrine role in several mammalian tissues. Recently studies have shown that stanniocalcin is highly expressed in the ovaries of mice and humans and we have investigated its expression in the mouse ovary during several physiological states to identify potential functional relationships. During postnatal 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 sites of STC protein localization are the theca and oocytes and after maturation it is also strongly concentrated in the corpora lutea. Over the estrous cycle the pattern of both STC gene expression and protein localization;lo not show dramatic changes though STC immunoreactivity (STCir) staining appears to be greatest during metestrus I. In the superovulation model, however, we observed a significant increase in STC messenger RNA (mRNA) levels after treatment with hCG implying regulation by LH. During gestation the expression of ovarian STC increases 15-fold and is localized to the theca-interstitial cells with lower expression also being found in the corpora lutea. STC also becomes detectable in the serum for the first time suggesting an endocrine role for STC during gestation. Interestingly the presence of a nursing litter appears to up-regulate STC gene expression in lactating mice suggesting 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 implying a role for STC in oocyte maturation. Stanniocalcin, to our knowledge, is unique because no other secreted proteins produced by the ovarian thecal-interstitial compartment are significantly induced during mouse pregnancy. In summary, our data provide evidence for the active regulation of STC expression in the ovary during gestation and lactation and therefore implies that STC is a new regulator of the gestational and nursing state.