Comparative analysis of the effects of ghrelin and un-acylated ghrelin upon luteinizing hormone secretion in male rats.

MARTINI AC; FERNÁNDEZ-FERNÁNDEZ R; TOVAR S; NAVARRO VM; VIGO E; VASQUEZ MJ; DAVIES JS; THOMPSON NM; AGUILAR E; PINILLA L; WELLS T; DIEGUEZ C; TENA-SEMPERE M

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2006 vol. 147 p. 2374 - 2382

0013-7227

Ghrelin, the endogenous ligando of GH secretagogue receptor type 1ª, has emerged as pleiotropic modulator of diverese biological functions, including energy homeostasis and, recently, reproduction. Although inhibitory actions of ghrelin on LH secretion and puberty onset have been reproted previously, the recptor mechanism mediating these actions, and the potencial gonadotropic effects of the unacylated isoform of ghrelin (UAG) remain nuclear. In this work, the effects of single and repeated administration of ghrelin or UAG on LH secretion were compared in pubertad and adult male rats. In addition, the effects of ghrelin were assessed in models of transient or persistent hypergonadotropism. Daily injection of gherlin or UAG throughout puberty similarly decreased LH levels and partially delayed balanopreputial separation. Likewise, chronic infusión of ghrelin or UAG to adult males resulted in significant decreases in circulating LH and FSH concentrations. Moreover, acute injection of ghrelin indiced a transient reduction in LH levels in freely moving males, an effect that was fully mimicked by administration of UAG. Yet, in contrast to ghrelin, UAG failed to modif. GH secretion. Finally, injection of ghrelin moderately, buy significantly, reduced the duration of LH secretory responses to the potent gonadotropin secretagogue kisspeptin-10, whereas ghrelin infusión in a model of chronic elevation of serum gonadotropin levels (the transgenic growth retarded male rat) evoked a significant reduction of LH concentrations. Altogether our present results further substantiate the inhibitory effect of ghrelin on basal and stimulated LH secretion in a wide array of experimental conditions. Moreover, our data are the first to demostrate the ability of UAG, originally considere dan inert form of the molecule, to mimic the actions of acylated ghrelin on LH release. The observations reinforce the contention that ghrelin, as putative signal for energy insuficiency, may operate as negative modifier of male puberty and LH secretion, an effect that might be, at least partially, conducted through a GH secretagogue receptor Type 1ª-independent mechanism.