Are immediate early genes involved in gonadotropin-releasing hormone receptor gene regulation? Characterization of changes in GnRH receptor (GnRH-R), c-fos, and c-jun messenger ribonucleic acids during the ovine estrous cycle
Padmanābhan, Vi | Dalkin, A. | Yasin, M. | Haisenleder, D.J. | Marshall, J.C. | Landefeld, T.D.
GnRH regulates the secretion and synthesis of gonadotropins by binding to specific receptors located in the plasma membrane of the pituitary gonadotropin. Like the concentration of the signaling ligand GnRH, the number of GnRH receptors (GnRH-R) varies dynamically with the changing endocrine milieu during the ovine estrous cycle. With the recent success in cloning of the mammalian GnRH-R gene, it is becoming increasingly evident that some of the changes in GnRH-R numbers may be mediated at least in part via changes in GnRH-R gene transcription. However,the regulatory steps involved in the GnRH-R transcription are unknown. The present studies were conducted to 1) characterize in detail the changes in GnRH-R gene expression during the 16-day ovine estrous cycle, 2) determine whether or not changes in GnRH-R gene expression during the estrous cycle are paralleled by alterations in the expression of c-fos and c-jun mRNAs, and 3) determine whether GnRH can induce expression of c-fos and c-jun mRNAs. Results revealed that concentrations of GnRH-R mRNA were highest on the day before estrus, when circulating LH concentrations were still low. GnRH-R mRNA concentrations declined steadily starting at 5 h postestrus, the time of the preovulatory LH surge, reaching their lowest levels by 24 h after estrus. Changes in c-jun mRNA levels, in general, paralleled changes in GnRH-R mRNA concentrations, being highest on the day before estrus and declining thereafter. c-Fos mRNA followed a different time course than c-jun mRNA, remaining elevated from Day 8 prior to estrus until the onset of estrus. c-Fos mRNA levels declined at the time of the surge and remained low until Day 5 postestrus. Similar decreases in GnRH-R and c-jun mRNA were also evident during the estradiol-induced LH surge in anestrous ewes. Studies conducted in ovariectomized hypogonadotropic lambs revealed that GnRH administration increases c-fos and c-jun mRNAs. Taken together, these studies suggest the intriguing possibility that immediate early genes may serve as transduction signals in the transcriptional activation of the GnRH-R gene.
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