Direct inhibitory actions of GnRH on accessory reproductive organs of rat

Recently gonadotropin releasing hormone (GnRH) and its agonistic analogs were demonstrated to have some direct actions in accessory reproductive organs. In our study the effects of GnRH and its analogs on some steroid hormone induced responses were investigated. GnRH and its analogs inhibited estradiol induced ornithine decarboxylase (ODC) and glucosamine-6-phosphate synthase activities in the uterus of rat. These enzymes which are markers for cell proliferation are regulatory enzymes in the biosynthetic pathways of polyamines and glycoproteins, respectively. Similarly, GnRH and its analogs also inhibited testosterone stimulated ODC activity in ventral prostate of rat. In addition, GnRH analog inhibited incorporation of radioactive precursors into RNA and protein induced by estradiol in uterus or dihydrotestosterone (DHT) in ventral prostate. In an effort to elucidate the mechanism of action of GnRH in uterus, it was found that GnRH analog treatment does not alter the estradiol receptor content in vivo. Also, GnRH does not show any effect on radioactive estradiol binding to its receptor in vitro. Hence, the inhibitory actions of GnRH in uterus may not involve estradiol receptors. However, GnRH analogs were found to have post-transcriptional effects. It was observed that DHT induced poly(A) polymerase activity in ventral prostate and estradiol induced poly(A) polymerase activity in uterus were inhibited by GnRH analog treatment. It was further observed that GnRH inhibited incorporation of [3H]uridine into poly(A)+ RNA of ventral prostate. This indicates that the inhibitory effects of GnRH involve post-transcriptional mechanisms.