Identification and Analysis of Two Novel Sites of Rat GnRH Receptor Gene Promoter Activity: The Pineal Gland and Retina

Abstract

Background and Aims: In mammals, activation of pituitary GnRH receptor (GnRHR) by hypothalamic GnRH increases the synthesis and secretion of LH and FSH, which, in turn, regulate gonadal functions. However, GnRHR gene (Gnrhr) expression is not restricted to the pituitary. Methods: To gain insight into the extrapituitary expression of Gnrhr, a transgenic mouse model that expresses the human placental alkaline phosphatase reporter gene driven by the rat Gnrhr promoter was created. Results: This study shows that the rat Gnrhr promoter is operative in two functionally related organs, the pineal gland, as early as embryonic day (E) 13.5, and the retina where activity was only detected at E17.5. Accordingly, Gnrhr mRNA were present in both tissues. Transcription factors known to regulate Gnrhr promoter activity such as the LIM homeodomain factors LHX3 and ISL1 were also detected in the retina. Furthermore, transient transfection studies in CHO and gonadotrope cells revealed that OTX2, a major transcription factor in both pineal and retina cell differentiation, is able to activate the Gnrhr promoter together with either CREB or PROP1, depending on the cell context. Conclusion: Rather than using alternate promoters, Gnrhr expression is directed to diverse cell lineages through specific associations of transcription factors acting on distinct response elements along the same promoter. These data open new avenues regarding GnRH-mediated control of seasonal and circadian rhythms in reproductive physiology.

An Induced Pluripotent Stem Cell Patient Specific Model of Complement Factor H (Y402H) Polymorphism Displays Characteristic Features of Age-Related Macular Degeneration and Indicates a Beneficial Role for UV Light Exposure

“…S3C). Currently, there is no documented expression of CGA in RPE cells; however, the expression of receptor (GNRHR, Gonadotropin‐releasing hormone receptor) has been detected in retinal tissues . Recoverin ( RCVRN) expression, which marks photoreceptor precursors, was also upregulated in high‐risk donors (Supporting Information Fig.…”

Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

“…The retina is a site of expression of many hormones, releasing factors, growth factors, and neuropeptides. Among this high diversity of autocrine and paracrine messengers, GH and GnRH, together with their respective receptors, are expressed in the retina [ 54 , 141 , 142 ]. This non-canonical distribution and expression has been described mainly in non-mammalian species, and there is increasing interest in their neurotrophic actions as an alternative when treating neurodegenerative diseases in the retina.…”

Rat Gnrhr promoter directs species-specific gene expression in the pituitary and testes of transgenic mice

“…Within the promoters of these species, several response elements and related transcription factors involved in the gonadotrope-specific and regulated expression of pituitary Gnrhr have been identified (Pincas et al 1998, Jorgensen et al 2004, Hapgood et al 2005, Granger et al 2006, Schang et al 2013a. Studies of these promoters in the ovary, placenta and hippocampus indicate that Gnrhr expression is driven by the same promoter with, however, different response elements and sets of transcription factors (Kang et al 2000, Cheng et al 2002, Schang et al 2011b, 2013b.…”

“…These transgenic mice were initially generated to improve in vitro analyses of the mechanisms involved in promoter activity and, most importantly, to explore, in vivo, the developmental pattern of rat Gnrhr promoter activity in the pituitary (Pincas et al 2001, Granger et al 2004, Schang et al 2013a. These transgenic mice also appeared to be powerful tools to identify novel tissues in which the Gnrhr promoter is active (Schang et al 2011a(Schang et al ,b, 2013b. Two transgenic mouse lines expressing ALPP under the control of the 3.3 or 1.1 kb rat Gnrhr promoter (referred to as 3.3-Gnrhr and 1.1-Gnrhr respectively) were generated.…”