Ontogenesis of Leptin Receptor in Rat Leydig Cells1

Abstract

There are still many controversies about the role of leptin in reproductive function and sexual development. We recently demonstrated that leptin receptors are expressed in rodent Leydig cells and that leptin has inhibitory effects on hCG-stimulated testosterone production by adult rat Leydig cells in culture. In this study, we evaluated the expression of leptin receptor (Ob-R) in rat testes from gestational to adult age in comparison with the pattern of expression of relaxin-like factor (RLF), a specific marker of Leydig cell differentiation status. Immunohistochemical analysis showed that, in prenatal life, Ob-R immunoreactivity was absent at early embryonic ages (E14.5) and appeared at a late embryonic age (E19.5); in postnatal life, immunoreactivity was evident only after sexual maturation (35-, 60-, and 90-days old), whereas it was absent in testes from sexually immature rats (7-, 14-, and 21-days old). Immunoreaction was always confined to Leydig cells and no signal of Ob-R was detected within the tubules. The pattern of expression of Ob-R during testicular development was similar with that of RLF immunoreactivity, which was present in mature fetal as well as adult-type Leydig cells. In contrast with the findings in the testis, in the hypothalamus, the immunohistochemical pattern of Ob-R was very similar between pre- and postpubertal life. Reverse transcription-polymerase chain reaction studies showed that Ob-R expression was present in embryonic, prepubertal, and adult rat testes; semiquantitative analysis showed that mRNA levels were much higher in late versus early embryonic testes, as well as in mature adults versus sexually immature testes, with a gradual increase from younger to older ages. Functional studies showed that, while leptin (150 ng/ml) significantly inhibited hCG-stimulated testosterone production in adult rat Leydig cells (46% reduction; P > 0.01), it did not modify prepubertal rat Leydig cells steroidogenic function in vitro. In conclusion, we showed that, in rat testis, Ob-R expression is characteristic of mature Leydig cells (fetal and adult type) and it is functional in adult but not prepubertal life.

Suppressor of Cytokine Signaling 7 Inhibits Prolactin, Growth Hormone, and Leptin Signaling by Interacting with STAT5 or STAT3 and Attenuating Their Nuclear Translocation

“…However, since many cells express LEPR, PRLR, or GH receptor, PRL-or GH-inducible negative transregulation of leptin activity cannot be excluded. Furthermore, considering that SOCS-7 expression is highest in the testis (6) and that leptin, GH, and PRL play important roles in testis physiology (22,23), our findings are indicative of a putative role for SOCS-7 in this organ.…”

Leptin and Its Receptor Are Expressed in the Testis and in the Epididymis of Young and Adult Pigs

“…In fact, in the rat, leptin was expressed in seminiferous tubules and in the interstitium of the adult gonads (Chen et al, 2008), whereas Ob-R was confined only in the Leydig cells of mature testes (Caprio et al, 2003), but it was absent in immature gonads. In contrast, in the mouse, leptin and its receptor were detected exclusively in germ cells of immature and mature testes (El-Hefnawy et al, 2000;Herrid et al, 2008).…”

“…In fact, Lep and/or Ob-R were detected in rodent testes (Caprio et al, 2003;El-Hefnawy et al, 2000;Herrid et al, 2008), in human testes and seminal plasma (Glander et al, 2002;Soyupek et al, 2005;Ishikawa et al, 2007), in human sperm (Aquila et al, 2005), in boar sperm (De Ambrogi et al, 2007), and in pig sperm (Aquila et al, 2008). Furthermore, a recent paper reported the effects of leptin treatment, alone or in combination with dietary energy restriction, on different reproductive parameters of male rats (Sirotkin et al, 2008).…”

Aging and pathogenesis of erectile dysfunction

“…41 Recent findings suggest a possible role of the adipocytesecreted hormone leptin, which increases with fat mass, 42 in this phenomenon. [43][44][45][46] Although it is generally assumed that testosterone enhances libido and frequency of sexual acts (see in Tenover 13 for review), recent studies 16,17 did not show any relationship between testosterone levels and ED prevalence and severity. In accordance with these latter studies, we did not find any correlation between testosterone levels and the severity of ED.…”