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Importance of the Paraventricular Nucleus of the Hypothalamus as a Component of a Neural Pathway between the Brain and the Testes that Modulates Testosterone Secretion Independently of the Pituitary

The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Catherine Rivier, Ph.D., The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: crivier{at}salk.edu.

We previously reported that in adult male rats, the intracerebroventricular (icv) injection of corticotropin-releasing factor (CRF) or the ß-adrenergic agonist isoproterenol (ISO) significantly inhibited the ability of human chorionic gonadotropin (hCG) to stimulate testosterone (T) secretion. The finding that this phenomenon also took place when LH release had been blocked with an LHRH antagonist suggested that icv CRF and ISO did not alter Leydig cell function by influencing the activity of pituitary gonadotrophs. We therefore proposed the existence of a neural pathway connecting the brain to the testes, whose activation by icv CRF or ISO interfered with T secretion. Based on the intratesticular injection of the transganglionic tracer pseudorabies virus, we recently identified the paraventricular nucleus (PVN) of the hypothalamus as a component of this neural link. The aim of the present work was to investigate the functional role of this brain area in mediating the ability of CRF and ISO to inhibit the ability of hCG to stimulate T secretion. We first demonstrated that local microinfusion of CRF or ISO directly into the PVN mimicked the effect of their icv injection, suggesting that the PVN does indeed represent a site of action of ISO and CRF in altering Leydig cell responsiveness to gonadotropin. In contrast, neither CRF nor ISO microinfusion into the central amygdala or the frontal cortex influenced hCG-stimulated T secretion. To further investigate the role of the PVN in ISO- and CRF-induced blunting of hCG stimulation of T, we determined the effect of icv CRF or ISO on testicular activity of rats with electrolytic lesions of the PVN. These lesions, which did not in themselves influence Leydig cell responsiveness to hCG, blocked the effect of both icv ISO and CRF on hCG-induced T release. Collectively, these results support the hypothesis that CRF- and ISO-induced activation of cells in the area of the PVN decreases the ability of gonadotropin to release T and suggests that this nucleus represents an important site of the proposed neural connection between the brain and the testes.

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