| The hypothalamic-pituitary-testes axis maintains reproduction by the coordinated release of GnRH from the hypothalamus. Applying an artificial continuous stimulus using the GnRH agonist, deslorelin, induces a chemically castrated state by suppressing serum testosterone levels. GnRH agonist administration has been shown to be completely reversible following short term exposure periods. However, there is evidence showing a correlation between dose and duration of exposure and latency period to full recovery. In chapter 1, we were able to confirm suppression of the reproductive axis by looking at gonadotropin subunit immunoreactivity in the anterior pituitary, quantifying plasma gonadotropin levels, and determining the degree of testicular atrophy by deslorelin administration. Full fertility is returning following deslorelin removal, but predominant suppression of FSHbeta persisted throughout the experiment. Chapter 2 shows that the predominant suppression of FSHbeta, in vivo, is a result of induction of the intrapituitary peptide ICER. We were able to confirm that suppression of FSHbeta was partially mediated through the loss of testosterone. In contrast, deslorelin suppressed LHbeta directly by down-regulating the GnRH receptor. Chapter 3 reports the effects of long-term high dose deslorelin exposure on body composition and blood biochemistry. Deslore lin increased body fat and we were able to confirm this effect was testosterone dependent. Liver and kidney function were altered following long term deslorelin exposure, an effect that was also partially mediated by the loss of testosterone. These results show for the first time that the long-term exposure to high dose deslorelin persistently and predominantly suppressed FSHbeta, an effect mediated by ICER, and increases body fat due to the loss of testosterone. |
