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

Abstract

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 follicles. 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.

Elevated hypothalamic aromatization at the onset of precocious puberty in transgenic female mice hypersecreting human chorionic gonadotropin: Effect of androgens

“…One effect occurring after the removal of gonadal steroid by Ovx, with the consequent loss of negative feedback at the central level, is the concomitant increase in GnRH pulse frequency (Levine and Ramirez, 1980). In this sense, the elevated Gnrh expression found in the POA-AH of WTOvx, hCGab+ and hCGab+ Ovx mice was in agreement with the elevated GnRH pulse frequency found in these groups, as well as with the diminished Gnrhr expression found in the pituitary, which reflects receptor downregulation (Mo et al, 2010). The loss of gonadal signals by Ovx in the TG females was able to elevate serum FSH levels as well as pituitary Fshb, Cga and Fst expression.…”

Role of Hormones in the Control of Reproductive Physiology and Reproductive Behavior

“…The GnRH receptor (GnRHR) is located at the level of the adenohypophysis (anterior pituitary gland) [12]. GnRH binds to extracellular loops of the GnRHR.…”