RGD Reference Report - Ghrelin Inhibits the Proliferative Activity of Immature Leydig Cells In Vivo and Regulates Stem Cell Factor Messenger RNA Expression in Rat Testis* - Rat Genome Database

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Ghrelin Inhibits the Proliferative Activity of Immature Leydig Cells In Vivo and Regulates Stem Cell Factor Messenger RNA Expression in Rat Testis*

Authors: Barreiro, ML  Gaytan, F  Castellano, JM  Suominen, JS  Roa, J  Gaytan, M  Aguilar, E  Dieguez, C  Toppari, J  Tena-Sempere, M 
Citation: Barreiro ML, etal., Endocrinology 2004 Jul 29;.
RGD ID: 1302206
Pubmed: PMID:15284210   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2004-0732   (Journal Full-text)

Ghrelin has emerged as putative regulator of an array of endocrine and non-endocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of the rat and human testis. Yet, testicular actions of ghrelin other than modulation of testosterone secretion remain unexplored. In the present study, we aimed at evaluating the effects of ghrelin upon proliferation of Leydig cell precursors during puberty, and after selective elimination of mature Leydig cells by treatment with ethylene dimethane sulfonate (EDS). In these settings, intratesticular injection of ghrelin significantly decreased the proliferative activity of differentiating immature Leydig cells, estimated by BrdU labeling. This response was selective and associated, in EDS-treated animals, to a decrease in the mRNA levels of stem cell factor (SCF), i.e. a key signal in spermatogenesis and putative regulator of Leydig cell development. Thus, the effects of ghrelin upon SCF gene expression were further evaluated. In adult rats, ghrelin induced a significant decrease in SCF mRNA levels in vivo. Such an inhibitory action was also detected in vitro using cultures of staged seminiferous tubules. The inhibitory effect of ghrelin in vivo was dependent on proper FSH input, as it was detected in hypophysectomized rats only after FSH replacement. Overall, it is proposed that acquisition of ghrelin expression by Leydig cell precursors during differentiation may operate as a self-regulatory signal for the inhibition of the proliferative activity of this cell type, through direct or indirect (i.e. SCF-mediated) mechanisms. In addition, we present novel evidence for the ability of ghrelin to modulate the expression of SCF gene, which may have implications for the mode of action of this molecule in the testis as well as in other physiological systems.

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Gene Kitlg KIT ligand Rattus norvegicus

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