Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis.

Abstract:

:Ghrelin has emerged as putative regulator of an array of endocrine and nonendocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of rat and human testis. Yet testicular actions of ghrelin, other than modulation of testosterone secretion, remain unexplored. In the present study we evaluated the effects of ghrelin on proliferation of Leydig cell precursors during puberty and after selective elimination of mature Leydig cells by treatment with ethylene dimethane sulfonate. In these settings, intratesticular injection of ghrelin significantly decreased the proliferative activity of differentiating immature Leydig cells, estimated by 5-bromodeoxyuridine labeling. This response was selective and associated, in ethylene dimethane sulfonate-treated animals, with a decrease in the mRNA levels of stem cell factor (SCF), i.e. a key signal in spermatogenesis and a putative regulator of Leydig cell development. Thus, the effects of ghrelin on SCF gene expression were 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, because 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 the SCF gene, which may have implications for the mode of action of this molecule in the testis as well as in other physiological systems.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Barreiro ML,Gaytan F,Castellano JM,Suominen JS,Roa J,Gaytan M,Aguilar E,Dieguez C,Toppari J,Tena-Sempere M

doi

10.1210/en.2004-0732

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

4825-34

issue

11

eissn

0013-7227

issn

1945-7170

pii

en.2004-0732

journal_volume

145

pub_type

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