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

Schang, Anne-Laure; Magre, Solange; Laverrière, Jean-Noël; Guillou, Aurélien; Coudouel, Noëlline; Wargnier, Richard; Cohen‐Tannoudji, Joëlle; Counis, Raymond

doi:10.1530/jme-12-0231

Cited by 6 publications

(12 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Receptors for LH, prolactin and GNRH have all been shown in earlier studies to be expressed in rat Leydig cells (Zhang et al 1995, Ariyaratne et al 2000, Ishaq et al 2013), but others have not been described previously. GPR182 is an adrenomedullin receptor that mediates a cAMP response to the peptide (Kapas et al 1995).…”

Section: Discussionmentioning

confidence: 90%

“…There are also some known differences in Leydig cell function between the species (e.g. Gnrhr is expressed in the rat testis but not the mouse testis (Ishaq et al 2013)), while a number of mouse transcripts in the Sanz et al (2013) study showed low expression in the rat arrays so that any effect of EDS would be difficult to show (e.g. Fetub).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Leydig cell-specific mRNA transcripts in the adult rat testis

O’Shaughnessy¹,

Monteiro²,

Fowler³

et al. 2014

Reproduction

View full text Add to dashboard Cite

The adult population of Leydig cells acts to secrete testosterone which is essential for reproductive health and fertility in the adult male. However, other physiological functions of these cells are uncertain, and to address this issue a cell ablation model has been used to identify Leydig cell-specific mRNA transcripts. Ethane dimethane sulphonate (EDS) was synthesised by a novel process and was used to ablate Leydig cells in adult male rats previously treated with butane dimethane sulphonate (busulphan) to delete the germ cell population. Levels of mRNA transcripts were measured in the testis using microarrays 1, 3, 5, 8 and 12 days after EDS injection. During this period, there was a significant change in the levels of 2200 different transcripts with a marked decline in the levels of canonical Leydig cell transcripts, such as Cyp11a1, Cyp17a1 and Insl3. A total of 95 transcripts showed a similar decline in expression after EDS treatment, suggesting that they have a Leydig cell-specific origin. Analysis of selected transcripts confirmed that they were expressed specifically in Leydig cells and showed that most had a late onset of expression during adult Leydig cell development. Apart from transcripts encoding components of the steroidogenic apparatus, the most common predicted function of translated proteins was endogenous and xenotoxicant metabolism. In addition, a number of transcripts encode acute-phase proteins involved in reduction of oxidative stress. Results show that, in addition to androgen secretion, Leydig cells may have a critical role to play in protecting the testis from damage caused by toxicants or stress.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Identification of Leydig cell-specific mRNA transcripts in the adult rat testis

O’Shaughnessy¹,

Monteiro²,

Fowler³

et al. 2014

Reproduction

View full text Add to dashboard Cite

show abstract

“…The 3.3‐Gnrhr‐ALPP mice were first used to analyse the spatial and temporal patterns of rat promoter activity during development in the hippocampus and testis. In both cases, we found that, in the transgenic mouse, the developmental profile of ALPP expression driven by the 3.3‐kb rat Gnrhr promoter reflected the expression pattern of Gnrhr in rat . Indeed, in the testis, ALPP transgene and rat Gnrhr expression was detected during foetal life and displayed the same biphasic profile characterised by high mRNA levels around birth, which initially declined and subsequently increased progressively at the end of the pre‐pubertal period (Fig.…”

Section: Species Specificities In the Mechanisms Regulating Gnrhr Expmentioning

confidence: 68%

“…In a third context, namely the adult pituitary after gonadectomy, the transgene was strongly up‐regulated. This mimicked the castration‐induced responsiveness of the rat Gnrhr but contrasted with the endogenous mouse Gnrhr , which was not significantly affected by castration . In parallel, using in situ analysis of transgene expression, we could localise rat Gnrhr promoter activity in a subset of neurones in the hippocampus and in foetal Leydig cells and progenitors of the adult Leydig cell population in the testis .…”

Section: Species Specificities In the Mechanisms Regulating Gnrhr Expmentioning

confidence: 78%

“…In addition, this promoter led to weak and variable luciferase expression in the testis, corresponding to 1% of the estimated level of expression in the pituitary . In our laboratory, we recently investigated Gnrhr expression in mouse testis but were unable to detect transcripts using conventional real‐time RT‐PCR . Gnrhr expression was detected only after a retrotranscription step specifically targeting Gnrhr transcripts.…”

Section: Species Specificities In the Mechanisms Regulating Gnrhr Expmentioning

confidence: 99%

See 1 more Smart Citation

Inside and Outside the Pituitary: Comparative Analysis of Gnrhr Expression Provides Insight into the Mechanisms Underlying the Evolution of Gene Expression

Schang

2015

J Neuroendocrinology

View full text Add to dashboard Cite

DNA cis-acting elements involved in gene regulation may actively contribute to adaptation processes because they are submitted to lower evolutionary constraints than coding DNA. In this regard, comparisons of the mechanisms underlying basal and regulated Gnrhr expression have revealed some features that promote stable and consistent Gnrhr expression in pituitary gonadotroph cells in different species. The presence of two divergent SF1 (NR5A1) response elements in all analysed mammalian Gnrhr promoters probably comprises one of the features that ensures reliable expression in the pituitary. By contrast, in other tissues, such as the hippocampus and testis, our analyses revealed dissimilar levels of Gnrhr expression among species. Indeed, Gnrhr was consistently expressed after birth in the rat but not the mouse hippocampus. Similar discrepancies were observed in foetal and adult testes. The ability of the rat promoter to drive reporter gene expression in the hippocampus and testis of transgenic mice just as it naturally directs the expression of the endogenous Gnrhr in rats strongly suggests that regulatory DNA sequences contained species-specific instructions prevailing over other controls. The major conclusion emerging from these studies is that Gnrhr promoter sequences are mainly responsible for directing transcriptional programmes and play a predominant role over the species-specific cell environment.

show abstract