. Passive immunization of lactating mice with stanniocalcin-1 antiserum reduces mammary gland development, milk fat content, and postnatal pup growth. Am J Physiol Endocrinol Metab 291: E974 -E981, 2006. First published June 13, 2006; doi:10.1152/ajpendo.00601.2005.-During pregnancy and lactation in rodents, stanniocalcin-1 (STC-1) production by the ovaries is upregulated markedly and released into the circulation. The mammary glands are one target of this systemically delivered hormone. The purpose of this study was to lower serum levels of STC-1 in lactating mice through passive immunization so as to monitor the effects on mammary gland function and postnatal pup growth. Passive immunization significantly reduced circulating hormone levels, and pup growth was significantly compromised (30%), even though control and experimental litters had ingested equal amounts of milk. When mammary glands were analyzed, the alveolar area was significantly reduced in antibody-treated mothers. An analysis of milk composition revealed no changes in lactose, protein, or electrolyte levels but an ϳ40% reduction in triglyceride levels. The latter was due to a significant reduction in mammary gland lipoprotein lipase activity and led to a significant buildup of triglycerides in the serum. Body fat content was also significantly reduced in pups from antibody-treated mothers, whereas pup fecal fat content was increased. In mothers, passive immunization also caused significant behavioral effects, in particular, increased locomotor and hindleg rearing activities. Collectively, the results suggest that systemically derived STC-1 has important effects on mammary gland development and the transfer of serum-based triglycerides into milk. Locomotor effects suggest that STC-1 also has a role in maternal behavior. development; lipoprotein lipase; behavior IN RODENTS, THE OVARIES HAVE THE HIGHEST LEVELS of stanniocalcin-1 (STC-1) gene expression. The gene is expressed predominantly by androgen-producing theca cells and interstitial cells. During nonpregnancy, ovarian STC-1 appears to be targeted locally to nearby corpus luteal cells, which contain high levels of receptors and where the ligand has pronounced inhibitory effects on progesterone release (38). An endocrine pathway becomes operative during pregnancy and lactation. In the pregnant mouse, the levels of ovarian STC-1 gene expression are upregulated 15-fold (10). Expression levels drop at parturition and then rise and remain high throughout the lactation phase. In parallel, serum levels of STC-1 rise and fall in concert with the changing levels of ovarian expression (10).During lactation, the high levels of ovarian STC-1 expression are sustained by the sucking stimulus, implying that the hormone is being targeted to the mammary glands. This notion has recently been given credence in studies on virgin, pregnant, and lactating rats (16). The virgin rat mammary gland has high levels of STC-1 receptors and also expresses the STC-1 gene. The majority of receptors are on microsomal membranes ...