Hormonal regulation of β-endorphin in the testis

Abstract

It is well established that β-endorphin has a regulatory influence on the reproductive function at the level of the hypothalamic-pituitary axis. However, recent immunohistochemical evidence demonstrated that β-endorphin is also present in the Leydig cells of fetal, neonatal and adult mice and hamsters. In addition, β-endorphin synthesis was localized in the Leydig cells of adult rats, leading to the hypothesis of a direct function of the peptide in the reproductive organs. Our interest was to investigate the role of β-endorphin at testicular level. We have demonstrated the presence of high-affinity opioid binding sites ( K d in the nanomolar range) in tubular homogenates and Sertoli cells in culture of adult (50 days) and immature (18 days post-natal) rat testes. Also, chronic β-endorphin treatment of the Sertoli cells significantly inhibited basal and FSH-stimulated androgen-binding protein production, this effect being prevented by the universal opiate antagonist naloxone. No opiate binding was observed on Leydig cell cultures. Furthermore, we have demonstrated that acute or chronic β-endorphin treatment does not affect testosterone production by Leydig cells in virto, consistent with the absence of receptors on these cells. On the other hand, fetal Leydig cells (21 days fetal life) in culture produced considerable amounts of β-endorphin. Also, fetal Leydig cells represented a preferred in virto system to study β-endorphin release since in adult cell culture a marked degradation of the peptide was detected (> 50%). β-endorphin accumulation for 3 and 5 days was markedly increased by inhibitors of steroid biosynthesis (1.5-fold); a significant reduction by GnRH at both days (by 50 − 30%) was observed, while by dexamethasone the reduction was only noted after 5 days of treatment (by 50%). Acute stimulation (3 h) of control cells with hCG enhanced by 10–12-fold the β-endorphin secretion. The hormone stimulation of β-endorphin production was not mediated by testosterone. On the contrary, inhibition of Leydig cells steroid biosynthesis markedly increased basal and hCG-stimulated β-endorphin production (150–200%), suggesting autocrine negative modulation of Leydig cell β-endorphin by androgen and/or its metabolites. In contrast, dexamethasone reduced basal and hCG-stimulated β-endorphin production (by 50%). Altogether these findings indicate that β-endorphin produced within the Leydig cells may behave as a paracrine inhibitor of the Sertoli cell function and demonstrate that the peptide production is under direct control by gonadotropins and is modulated by steroids.