Neuroendocrine control of male reproductive function. The opioid system as a model of control at multiple sites.

It is known that the same peptide can be identified in different secretory tissues and in the central nervous system (CNS). We now provide evidence that the same peptides can be found in different organs related to the control of a single function, and speculate on the possibility that this reflects a common neuroendocrine programming. Endogenous opioid peptides (EOP) inhibit the reproductive function acting via the CNS. EOP inhibit gonadotropin secretion in rodents and humans via inhibition of GnRH release and have direct inhibitory actions at the pituitary level via specific binding sites on the gonadotrophs. However, EOP can also be synthesized in the testis and in different compartments of the male genital tract. Several findings indicate that EOP of the reproductive tract have a local, paracrine role. These include: (1) the detection of significant beta-endorphin (beta-EP) production by rat Leydig cells (Lc) in cultures; (2) the hormonal regulation of Lc beta-EP production by positive (gonadotropins) and negative (steroids, glucocorticoids, GnRH) factors; (3) the presence of opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells (Sc) in culture of adult and immature rat testes; (4) the inhibition of basal and FSH-stimulated ABP production by Sc in culture when chronically exposed to beta-EP treatment; (5) the detection of high levels of beta-EP and met-enkephalin in human semen with values 6-12 times higher than in plasma; (6) the evidence for inhibitory functions of seminal opioids on sperm motility, vas deferens muscle contraction and partner immune system. Thus the same peptides, i.e. EOP, may control the reproductive function at multiple sites, operating as a multimessenger system in which the central and peripheral level are unified by the common chemical and inhibitory nature of the message.