Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Michael Lehman

Abstract

Excess androgen exposure during fetal life in the ewe permanently alters the number of agouti-related peptide (AgRP) neurons and their projections, suggesting a possible mechanism by which prenatal testosterone may contribute to insulin resistance and an increased risk of obesity in women with polycystic ovarian syndrome (PCOS). Using immunocytochemistry, we found a decrease of insulin receptors colocalized with AgRP in the arcuate nucleus of the hypothalamus in prenatal testosterone treated sheep, but no changes in colocalization with proopiomelanocortin (POMC). In addition, characterization of leptin-induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin signalling, was mapped in the hypothalamus and preoptic area of control sheep. We found that pSTAT3 colocalizes with POMC-ir neurons, minimally with kisspeptin, and is not co-expressed with GnRH. Overall, these results may lay the foundation for manipulation studies that will attempt to help address the metabolic and reproductive deficits seen in women with PCOS.

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