Endocrine Abstracts

The epidemic-like increase in obesity in young people is paralleled by a rise in related diseases such as PCOS, especially in pubertal girls. Kisspeptins, encoded by the KiSS1 gene, are firmly linked with the normal control of the reproductive system and loss-of-function mutations are associated with absence of puberty. Although KiSS1 is predominantly expressed in the hypothalamus (HYP), we detected KiSS1 mRNA in rat pituitary (PIT) and adipose tissue (FAT) using realtime RT-PCR (Brown et al. 2008). KiSS1 mRNA was regulated by sex steroids and nutritional status in these tissues. We also determined that KiSS1 is expressed in human female abdominal fat. In the present work we investigated whether KiSS1 expression was compromised in a novel rat model of PCOS (Manneras et al. 2007). In a variation of this model, weanling female rats (postnatal day 21) were fitted with osmotic minipumps (Alzet #2002) that continuously released dihydrotestosterone (DHT; 83 μg/day; 14d). Control rats received sham surgery alone. Rats were weighed daily and inspected for vaginal opening (VO; first ovulation) until sacrifice (PD 35). Total RNA was isolated from HYP, PIT, ovary and visceral fat. The expression of KiSS1, leptin (ob) and gpr54 (encoding the receptor for kisspeptin) was quantified by realtime RT-PCR. VO was absent in all DHT-treated rats, ovarian weight was decreased (P<0.001; n=8), whereas bodyweight was significantly increased (P<0.001). Although DHT treatment had no effect on KiSS1 mRNA in HYP, it significantly elevated levels in PIT (P<0.01), ovary (P<0.05) and FAT (P<0.02). Gpr54 expression was significantly increased in all tissues analysed, whereas ob mRNA was only increased in fat and ovary. In conclusion, brief treatment with DHT induced changes in KiSS1, gpr54 and ob expression that may contribute to the multiple tissue abnormalities associated with PCOS. Supported by IWK, Atlee Endowment and UIMRF/Capital Health.