Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Graham Wagner

Second Advisor

Dr. John Ciriello

Abstract

In lactating mice, circulating stanniocalcin-1 (STC-I) stimulates mammary gland lipoprotein lipase (LPL) activity and affects maternal behaviour. LPL is also found in white adipose tissue (WAT) which is heavily targeted by STC-1. However, during late pregnancy and lactation, LPL activity is high in the mammary gland, but low in WAT. Since both organs are exposed to circulating STC-1 during late pregnancy and lactation, and assuming that STC-1 is a stimulator of LPL in both tissues, one would expect to see a decrease in WAT STC-1 receptor levels at this time. This would decrease the sensitivity of WAT to the presumptive stimulatory effects that STC-1 has on WAT LPL activity. In support of this hypothesis, the results showed that STC-1 receptor levels were significantly reduced in the mitochondria and microsomal membranes of WAT on the 14th day of pregnancy. However, receptor levels rose after parturition and were restored to those of pre-pregnancy in lactation. Interestingly, WAT STC-1 gene expression was also downregulated in pregnancy and then restored in lactation, suggesting a switch in the source of STC-1 that targets WAT. In addition, both STC-1 and its receptor co-localized in WAT adipocyte nuclei, perhaps to modulate WAT LPL activity. Because STC-1 affects maternal behaviour in lactating rodents, rat forebrain was mapped for the presence of STC-1 binding sites. Binding sites (putative receptors) were predominantly observed in ependymal cells lining the anterior third ventricle and in circumventricular organs, areas associated with regulation of body fluid and ion homeostasis. These data suggest that STC-1 may be associated with neuronal pathways involved in calcium/phosphate and fluid homeostasis. However, the manner in which STC-1 signalling on these sites could impact maternal behaviour will have to be addressed in future studies.

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