Specific action of Ghrelin on rat Leydig cell function: modulatory effect of fasting.

MARÍA O. SUESCUM, A. GIOVAMBATTISTA, J. PIERMARIA, E. SPINEDI AND RICARDO S. CALANDRA

New Orleans, USA

Congreso; Annual Meeting of the American Endocrine Society; 2004

American Endocrine Society

Title: Specific action of Ghrelin on rat Leydig cell function: modulatory effect of fasting. Maria O Suescun 1,2 Andres Giovambattista1,2  JudithPiermaria1  Eduardo Spinedi 3 and Ricardo S Calandra 1,2  1 Reproductive Endocrinology. IMBICE. La Plata. BA. Argentina. 2 Facultad de Cs. Exactas, UNLP, La Plata. BA. Argentina. and 3 Neuroendocrine Unit. IMBICE, La Plata, BA, Argentina. It is well known that reproductive function is influenced by the nutritional status of the organism (1). Individual feeding behavior and body weight control are managed at the hypothalarnic, arcuate nucleus, level. However, sorne peripheral signals, such as adipocyte- and stomach-derived Leptin and Ghrelin (Ghr), respeetively, link energetic balance and reproduction (2). Both peptide hormones act at the hypothalamic level exerting their, respective, anorexigenic and orexigenic actions through specific receptors. Recently it has been demonstrated the presence of GHSr in rat testis (3) and Ghr effect on testicular testosterone production (4). The present study was designed to determine whether Ghr possess a direct modulatory effect on Leidig cells (LC) and if changes in energy balance are able to influence the effect of Ghr on testicular function. For these aims we explored the effect of different concentrations of Ghr (1-100 nM) on testosterone production by purified LC, from non fasting (control, CT) and 96 h-fasted (AY) adult Fisher 344 rats, incubated during 3 h in basal and hCG-stimulated conditions. The results indicated that testosterone (basal and hCG-stirnulated) production was lower in AY than in CT LC (basal, AY: 0.54 ± 0.05 vs. CT: 1.09 ± 0.06: hCG 10ng/ml, AY: 2.70 ± 0.34 vs. CT: 3.99 ± 0.15 ng/105 cells; p < 0.05). We found an inhibitory effect of Ghr (all tested doses) on hCG­stimulated testosterone production by control LC. Conversely, in purifled LC from fasted rats, a lack of ihe inhibitory effect of Ghr was observed. Finally, purifled LC were preincubated for 30 min, with different concentrations (10, 100 and 1,000 nM) of the low affinity Ghr inverse agonist (Arg1 -Phe5-Trp7,9-Leu11 -Substanee P) (5): then, different doses of Ghr (1-100 nM) was added to the tubes and incubated as described above. The results indicated that the inhibitory effects of 1 and 10 nM, but not 100 nM, Ghr on testosterone production by control LC were fuIly abolished in the presence of 1,000 nM Ghr inverse agonist. Our data support that Ghr could be a direct, specific negative modulator of LC function, and that the absence of its effect during fasting could result in an adaptive change for gonadal function preservation during negative energetic balance condition. References: 1.SmalI CJ, Stanley SA, Blooin SR. Appetite control and reproduction: leptin and beyond. Semin Reprod Med 2002; 20:389-398. 2.   Ziginan JM, Elmquist JK. From anorexia to obesity-the yin and yang of body weight control. Endocrinology 2003; 144:3749-3756. 3.Tena-Sempere M, Barreiro ML. Gonzalez, LC, Gaytan F, Zhang FP. Caminos JE. Pinilla L, Casanueva EF, Dieguez C, Aguilar E. Novel expression and functional role of ghrelin in rat testis. Endocrinology 2002; 143:717-725. 4.Tena-Sempere M. Pinilla L, Gonzalez LC. Dieguez C. Casanueva FF. Aguilar E. Leptin inhibits testosterone secretion from adult rat testis in vitro. JEndocrinol. 1999; 161:211-218. 5.Asakawa A, Inuí A, Kaga T, Katsuura G. Fujimiya M. Fujino MA. Kasuga M. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003: 52:947-952. Financial Support: Beca Carrillo-Oñativia 2003 and PICT 5/5191/99 (to E.S.)