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Karger AG","issue":"2","license":[{"start":{"date-parts":[[2012,8,25]],"date-time":"2012-08-25T00:00:00Z","timestamp":1345852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,8,25]],"date-time":"2012-08-25T00:00:00Z","timestamp":1345852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background and Aims:&lt;\/i&gt;&lt;\/b&gt; 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 &lt;i&gt;(Gnrhr)&lt;\/i&gt; expression is not restricted to the pituitary. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; To gain insight into the extrapituitary expression of &lt;i&gt;Gnrhr&lt;\/i&gt;, a transgenic mouse model that expresses the human placental alkaline phosphatase reporter gene driven by the rat &lt;i&gt;Gnrhr&lt;\/i&gt; promoter was created. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; This study shows that the rat &lt;i&gt;Gnrhr&lt;\/i&gt; 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, &lt;i&gt;Gnrhr&lt;\/i&gt; mRNA were present in both tissues. Transcription factors known to regulate &lt;i&gt;Gnrhr&lt;\/i&gt; 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 &lt;i&gt;Gnrhr&lt;\/i&gt; promoter together with either CREB or PROP1, depending on the cell context. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Rather than using alternate promoters, &lt;i&gt;Gnrhr&lt;\/i&gt; 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.<\/jats:p>","DOI":"10.1159\/000337661","type":"journal-article","created":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T09:54:49Z","timestamp":1331632489000},"page":"115-131","source":"Crossref","is-referenced-by-count":12,"title":["Identification and Analysis of Two Novel Sites of Rat GnRH Receptor Gene Promoter Activity: The Pineal Gland and 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