Developmental and hormonal regulation of leptin receptor (Ob-R) messenger ribonucleic acid expression in rat testis

In target tissues, leptin receptor (Ob-R) gene expression results in an arr ay of alternatively spliced isoforms (Ob-Ra to Ob-Rf) with different functi onal features. Recent evidence has pointed to a direct role of leptin in th e control of testicular function. However, complete elucidation of the patt ern of Ob-R gene expression in the male gonad is still pending. The focus o f this study was to characterize in detail the developmental pattern of exp ression and hormonal regulation of Ob-R gene in rat testis. To this end, th e overall expression of Ob-R mRNA was compared to that of the fully functio nal, long Ob-Rb isoform in different experimental settings, using semiquant itative reverse transcription-polymerase chain reaction. Expression of Ob-R mRNA was detected in testes from 15-, 30-, 45-, and 75-day-old rats at rat her constant relative levels. In contrast, testicular expression of Ob-Rb m RNA was higher in pubertal testes (15- to 30-day-old rats) and declined in adulthood. In testes from 30-day-old animals, analysis of isoform distribut ion revealed that, in addition to abundant Ob-Rb mRNA levels, expression of Ob-Ra, Ob-Rf, and, to a lesser extent, Ob-Rc and Ob-Re messages is detecte d. Testicular Ob-R mRNA expression appeared sensitive to neonatal imprintin g as neonatal treatment with estradiol benzoate (500 mug/rat; Day 1 postpar tum) resulted in a persistent increase (P < 0.01) in the relative expressio n level of Ob-R mRNA, a phenomenon only partially mimicked by neonatal supp ression of serum gonadotropins by means of LHRH-antagonist administration. In addition, neonatal estrogenization differentially altered the pattern of expression of Ob-R isoforms in adult rat testis, as expression of Ob-Rb mR NA was decreased to undetectable levels, whereas that of Ob-Rc remained una ltered, and Ob-Ra, Ob-Rf, and, to a lesser extent, Oh-Re mRNA levels were s ignificantly increased (P < 0.01) by neonatal exposure to estrogen. Finally , down-regulation of testicular Ob-R gene expression by homologous and hete rologous signals was demonstrated as relative levels of Ob-R and Ob-Rb mRNA s were significantly decreased (P < 0.01), in a coordinate manner, in rat t estis after exposure to human recombinant leptin in vitro, and after stimul ation with hCG and FSH in vivo. In conclusion, our results indicate that te sticular Ob-R gene expression is developmentally regulated, imprinted by th e neonatal endocrine milieu, and sensitive to regulation by leptin and gona dotropins. The ability of pivotal signals in testicular function to regulat e Ob-R gene expression further supports the contention of a direct role of leptin in functional control of the rat testis.