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 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.
Mo
YaQin
Y
Department of Obstetrics & Gynecology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
Peng
Ping
P
Zhou
Ran
R
He
ZuanYu
Z
Huang
LiLi
L
Yang
DongZi
D
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008186:Luteolytic Agents / Q000494:pharmacology; D010049:Ovarian Diseases / Q000139:chemically induced / Q000188:drug therapy; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017329:Triptorelin Pamoate / Q000494:pharmacology*
D006727:Hormone Antagonists; D008186:Luteolytic Agents; D012333:RNA, Messenger; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide; C062876:cetrorelix