scholarly journals Influence of fetal Leydig cells on the development of adult Leydig cell population in rats

2018 ◽  
Vol 64 (3) ◽  
pp. 223-231 ◽  
Author(s):  
Dong-Mei SU ◽  
Ying FENG ◽  
Lin WANG ◽  
Yi-Lun WU ◽  
Ren-shan GE ◽  
...  
Reproduction ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 851-858 ◽  
Author(s):  
P J O'Shaughnessy ◽  
I D Morris ◽  
P J Baker

Leydig cells in the rat testis can be specifically ablated with ethane dimethane sulfonate (EDS) and will subsequently re-generate. In this study, we have characterized Leydig cell re-generation and expression of selected cell-signaling molecules in a germ cell-free model of EDS action. This model offers the advantage that re-generation occurs on a stable background without confounding changes from the regressing and repopulating germ cell population. Adult rats were treated with busulfan to remove the germ cell population and Leydig cells were then ablated with EDS. Testicular testosterone levels declined markedly within 24 h of EDS treatment and started to recover after 8 days. After EDS treatment there were marked declines in levels of Leydig cell-specific mRNA transcripts coding for steroidogenic enzymes cytochrome P450 11a1 (Cyp11a1), cytochrome P450 17a1 (Cyp17a1), 3β-hydroxysteroid dehydrogenase type 1 (Hsd3b1), 17β-hydroxysteroid dehydrogenase type 3 (Hsd17b3) and the LH receptor. Levels of all transcripts recovered within 20 days of EDS treatment apart from Hsd17b3, which remained undetectable up to 20 days. Immunohistochemical localization of CYP11A1 during the phase of early Leydig cell re-generation showed that the Leydig cell precursors are spindle-shaped peritubular cells. Studies on factors which may be involved in Leydig cell re-generation showed there were significant but transient increases in platelet-derived growth factor A (Pdgfa), leukemia inhibitory factor (Lif), and neurofilament heavy polypeptide (Nefh) after EDS, while desert hedgehog (Dhh) levels declined sharply but recovered by 3 days. This study shows that the Leydig cell precursors are peritubular cells and that expression of Pdgfa and Lif is increased at the start of the re-generation process when precursor proliferation is likely to be taking place.


Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 417-425 ◽  
Author(s):  
Yuichi Shima ◽  
Kanako Miyabayashi ◽  
Takashi Baba ◽  
Hiroyuki Otake ◽  
Sanae Oka ◽  
...  

Adrenal 4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) (Nr5a1) is a nuclear receptor essential for reproductive tissue development and endocrine regulation. This factor is expressed in steroidogenic tissues (e.g. adrenal glands and gonads), and expression of this factor is tightly regulated in a tissue and cell type-specific manner. Our previous studies have identified tissue and cell type-specific enhancers in the introns of the Ad4BP/SF-1 gene in fetal adrenal glands, ventromedial hypothalamus, and pituitary gonadotrope. Characterization of the enhancers had provided new insights into tissue and cell development. However, these studies have failed to identify any gonad-specific enhancer. Here, we identified a fetal Leydig cell-specific enhancer in the upstream region of the mouse Ad4BP/SF-1 gene using transgenic mouse assays. Alignment of the upstream regions among vertebrate animal species demonstrated that the enhancer consisted of three conserved regions, whereby the most highly conserved region contained an Ad4BP/SF-1 binding sequence and an E-box. Mutation of each sequence abolished the enhancer activity and led to a loss of reporter gene expression. These results suggested that Ad4BP/SF-1 gene expression in the fetal Leydig cell is regulated by a yet unidentified E-box binding protein(s) and by an autoregulatory loop formed by Ad4BP/SF-1. Although fetal Leydig cells have been thought to play crucial roles for masculinization of various fetal tissues through androgen production, other functions have remained elusive. Our identification of a fetal Leydig cell-specific enhancer in the Ad4BP/SF-1 gene would be a powerful tool to address these gaps in the knowledge base.


Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3279-3284 ◽  
Author(s):  
P. J. O’Shaughnessy ◽  
L. M. Fleming ◽  
G. Jackson ◽  
U. Hochgeschwender ◽  
P. Reed ◽  
...  

Abstract Adult Leydig cell steroidogenesis is dependent on LH but fetal Leydig cells can function independently of gonadotropin stimulation. To identify factors that may be involved in regulation of fetal Leydig cells expressed sequence tag libraries from fetal and adult testes were compared, and fetal-specific genes identified. The ACTH receptor [melanocortin type 2 receptor (Mc2r)] was identified within this fetal-specific group. Subsequent real-time PCR studies confirmed that Mc2r was expressed in the fetal testis at 100-fold higher levels than in the adult testis. Incubation of fetal or neonatal testes with ACTH in vitro stimulated testosterone production more than 10-fold, although ACTH had no effect on testes from animals aged 20 d or older. The steroidogenic response of fetal and neonatal testes to a maximally stimulating dose of human chorionic gonadotropin was similar to the response shown to ACTH. The ED50 for ACTH, measured in isolated fetal and neonatal testicular cells, was 5 × 10−10m and the lowest dose of ACTH eliciting a response was 2 × 10−11m. Circulating ACTH levels in fetal mice were around 8 × 10−11m. Neither α-MSH nor γ-MSH had any effect on androgen production in vitro at any age. Fetal testosterone levels were normal in mice that lack circulating ACTH (proopiomelanocortin-null) indicating that ACTH is not essential for fetal Leydig cell function. Results show that both LH and ACTH can regulate testicular steroidogenesis during fetal development in the mouse and suggest that fetal Leydig cells, but not adult Leydig cells, are sensitive to ACTH stimulation.


1987 ◽  
Vol 37 (3) ◽  
pp. 727-738 ◽  
Author(s):  
Larry Johnson ◽  
Kathleen S. Matt ◽  
Andrzej Bartke ◽  
Hung B. Nguyen ◽  
Huong T. Le

1994 ◽  
Vol 266 (6) ◽  
pp. E975-E979 ◽  
Author(s):  
G. P. Risbridger ◽  
A. Davies

The cytotoxic drug ethane dimethane sulfonate (EDS) has been extensively used as a means of studying the regeneration of Leydig cells in the adult rat testis. This study used the EDS-treated rat testis as a source of material for the isolation of regenerating Leydig cells and their precursors and describes the procedures required for the isolation of these cell preparations. As early as 13-15 days after EDS, cells in the precursor fraction can bind low, but detectable, levels of iodinated purified human chorionic gonadotropin. However, no luteinizing hormone (LH) response was detected in terms of steroid production. The precursor fraction of cells isolated from the EDS-treated rat testis 17-19 days after the administration of EDS was heterogeneous in light-microscopic appearance, but identifiable Leydig-like cells were present. The cells in this fraction were the first to exhibit the ability to respond to LH with the production of detectable levels of the reduced androgen, 5 alpha-androstane-3 alpha,17 beta-diol. The amount of androgen produced by both the Leydig cell and precursor fractions had increased by 21 days after EDS and reached the levels produced by immature adultlike Leydig cells, which can be isolated from the 20-day-old rat testes. These studies demonstrate that steroidogenically responsive precursor forms of Leydig cells can be isolated from the EDS-treated testes 17-19 days after depletion of the adult Leydig cell population.


2014 ◽  
Author(s):  
Laura O'Hara ◽  
Kerry McInnes ◽  
Ioannis Simitsidellis ◽  
Steph Morgan ◽  
Laura Milne ◽  
...  

2014 ◽  
Author(s):  
W Colin Duncan ◽  
Fiona Connolly ◽  
Lyndsey Boswell ◽  
Graeme Burt ◽  
Alan S McNeilly ◽  
...  

2011 ◽  
Vol 25 (7) ◽  
pp. 1211-1222 ◽  
Author(s):  
Soichi Yamashita ◽  
Ping Tai ◽  
Jean Charron ◽  
CheMyong Ko ◽  
Mario Ascoli

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