Regulation of Gonadotropin-Releasing Hormone (GnRH) Receptor-I Expression in the Pituitary and Ovary by a GnRH Agonist and Antagonist

The aim of the current study was to examine the effects of gonadotropin-releasing hormone agonist (GnRH-a) and antagonist (GnRH-ant) on the expression of GnRH receptor-I (GnRHR-I) in pituitary and ovaries in cyclophosphamide (CTX) chemotherapeutic rats and to investigate the possible mechanism of interventions of GnRH-a and GnRH-ant in CTX-induced ovarian damage. In total, 36 female rats were distributed into 6 groups at random: normal saline (NS) group, CTX group, GnRH-a + NS group, GnRH-a + CTX group, GnRH-ant + NS group, and GnRH-ant + CTX group. After the rats were killed, the expression of GnRHR-I messenger RNAs (mRNAs) and proteins in pituitary and ovaries were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. The distribution of GnRHR-I in various compartments of the ovaries was observed by immunohistochemistry. Significant downregulation of GnRHR-I mRNA and protein expression in the pituitary were observed after treatment with GnRH-a or GnRH-ant. Moreover, GnRH-ant was more potent for this direct and fast inhibition. In ovary, GnRHR-I expression was significantly downregulated by GnRH-a. Although GnRH-ant slightly decreased the ovarian expression of GnRHR-I mRNA, the protein level was only weakly changed. In the ovarian compartment, GnRHR-ant groups had markedly GnRHR-I expression in early and late growing follicles compared to GnRHR-a groups that exhibited decreased expression of GnRHR-I, especially in late growing folicles. In summary, this study presents evidence for the different regulating effects of GnRH-a and GnRH-ant on the expression of GnRHR-I in pituitary and ovaries, which may provide insight into the mechanism of GnRH-a and GnRH-ant interventions on chemotoxic ovarian damage.