The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably in gonads. However, mechanisms underlying the gonad-specific expression of Gnrhr are not well understood. Here, Gnrhr expression was analysed in the developing testes and pituitaries of rats and transgenic mice bearing the human placental alkaline phosphatase reporter gene (ALPP) under the control of the rat Gnrhr promoter. We showed that the 3.3 kb, but not the pituitary-specific 1.1 kb promoter, directs ALPP expression exclusively to testis Leydig cells from embryonic day 12 onwards. Real-time PCR analysis revealed that promoter activity displayed the same biphasic profile as marker genes in Leydig cells, i.e. abrupt declines after birth followed by progressive rises after a latency phase, in coherence with the differentiation and evolution of foetal and adult Leydig cell lineages. Interestingly, the developmental profile of transgene expression showed high similarity with the endogenous Gnrhr profile in the rat testis, while mouse Gnrhr was only poorly expressed in the mouse testis. In the pituitary, both transgene and Gnrhr were co-expressed at measurable levels with similar ontogenetic profiles, which were markedly distinct from those in the testis. Castration that induced pituitary Gnrhr up-regulation in rats did not affect the mouse Gnrhr. However, it duly up-regulated the transgene. In addition, in LβT2 cells, the rat, but not mouse, Gnrhr promoter was sensitive to GnRH agonist stimulation. Collectively, our data highlight inter-species variations in the expression and regulation of Gnrhr in two different organs and reveal that the rat promoter sequence contains relevant genetic information that dictates rat-specific gene expression in the mouse context.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1530/JME-12-0231 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated Gαs-cAMP pathway and AR-YAP1 axis.
Cell Biosci
November 2021
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Background: Gonadotropin-releasing hormone receptor (GnRHR) transmits its signal via two major Gα-proteins, primarily Gαq and Gαi. However, the precise mechanism underlying the functions of Gαs signal in prostate cancer cells is still unclear. We have previously identified that GV1001, a fragment of the human telomerase reverse transcriptase, functions as a biased GnRHR ligand to selectively stimulate the Gαs/cAMP pathway.
View Article and Find Full Text PDFProliferating primary pituitary cells as a model for studying regulation of gonadotrope chromatin and gene expression.
Mol Cell Endocrinol
August 2021
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel. Electronic address:
The chromatin organization of the gonadotropin gene promoters in the pituitary gonadotropes plays a major role in determining how these gene are activated, but is difficult to study because of the low numbers of these cells in the pituitary gland. Here, we set out to create a cell model to study gonadotropin chromatin, and found that by optimizing cell culture conditions, we can maintain stable proliferating cultures of primary non-transformed gonadotrope cells over weeks to months. Although expression of the gonadotropin genes drops very low, these cells are enriched in gonadotrope markers and respond to GnRH.
View Article and Find Full Text PDFAndrogen receptor positively regulates gonadotropin-releasing hormone receptor in pituitary gonadotropes.
Mol Cell Endocrinol
June 2021
Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, 92093, USA. Electronic address:
Within pituitary gonadotropes, the gonadotropin-releasing hormone receptor (GnRHR) receives hypothalamic input from GnRH neurons that is critical for reproduction. Previous studies have suggested that androgens may regulate GnRHR, although the mechanisms remain unknown. In this study, we demonstrated that androgens positively regulate Gnrhr mRNA in mice.
View Article and Find Full Text PDFSignaling pathways and promoter regions that mediate pituitary adenylate cyclase activating polypeptide (PACAP) self-regulation in gonadotrophs.
Mol Cell Endocrinol
July 2020
Department of Anatomical Sciences and Neurobiology, Louisville, KY, 40202, USA; Division of Endocrinology & Metabolism, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, 40202, USA. Electronic address:
Pituitary adenylate cyclase-activating polypeptide (PACAP) is thought to play a role in the development and regulation of gonadotrophs. PACAP levels are very high in the rodent fetal pituitary, and decline substantially and rapidly at birth, followed by a significant rise in FSHβ and GnRH-R expression. Because there is evidence that PACAP stimulates its own transcription, we propose that this self-regulation is interrupted around the time of birth.
View Article and Find Full Text PDFConditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse.
Sci Rep
July 2019
Department Biomedical Science, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Extracellular-signal-regulated kinases (ERK) 1 and 2 regulate many aspects of the hypothalamic-pituitary-gonadal axis. We sought to understand the role of ERK1/2 signaling in cells expressing a Cre allele regulated by the endogenous GnRHR promoter (GRIC-ERKdko). Adult female GRIC-ERKdko mice were hypogonadotropic and anovulatory.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!