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

Abstract

We previously reported that in adult male rats, the intracerebroventricular (icv) injection of corticotropin-releasing factor (CRF) or the beta-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.

Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex

“…This is consistent with our previous biochemical observations on biochemical markers of cell number (Garofolo et al, 2003). ␤AR stimulation reduces testosterone levels (Selvage and Rivier, 2003), which may provide a component of the sex-selective actions on this region. In contrast, females were targeted for effects on the hippocampus and somatosensory cortex.…”

Androgen receptor expressing neurons that project to the paraventricular nucleus of the hypothalamus in the male rat

“…Similarly, structures thought to control the production of gonadotropic hormones, including the periventricular preoptic and anteroventral periventricular nuclei (Wiegand and Terasawa, 1982) also showed significant complements of double-labeled cells. This distribution suggests that androgenic regulation of gonadotropinreleasing hormone release and reproductive behavior is not entirely restricted to components of the gonadal axis, but may also rely on concurrent regulation of both the neuroendocrine and autonomic-related branches of the PVN (Selvage and Rivier, 2003;Selvage et al, 2004, Ulrich-Lai et al, 2006. This is consistent with the disruptive effects of adrenalectomy and sympathetic blockade on testosterone secretion, androgenic regulation of gonadotropin-releasing hormone and luteinizing hormone release, and sexual behavior (reviewed in Kalra and Kalra, 1983;Levine et al, 1991;Herbison, 2006;and see Poggioli et al, 1984).…”

Ultradian rhythmicity and induced changes in salivary testosterone

“…Similar rapid responses have been reported in males in literature in response to various stimuli such as maximal exercise (Busko and Opaszowski 2005;Crewther et al 2007) and exposure to potential mates (Roney et al 2007). Research has described direct neural links between the brain and testes suggesting that hormonal secretion may also be regulated through a rapid neural mechanism (Selvage and Rivier 2003;Lee et al 2004). Although speculative, the high degree of sympathetic activation associated with supra-maximal exercise may promote testosterone production due to increased sympathetic tone to the Leydig cells (Frungieri et al 2002).…”