A Hypothalamic-Testicular Neural Pathway Is Influenced by Brain Catecholamines, But Not Testicular Blood Flow

Abstract

We previously reported the existence of a descending multisynaptic, pituitary-independent, neural pathway between the hypothalamus and the testes in the male rat. Stimulation of this pathway by the intracerebroventricular (icv) injection of IL-1beta or corticotropin-releasing factor blunts the testosterone (T) response to human chorionic gonadotropin (hCG). This response is mediated at least in part by catecholamine beta-adrenergic receptor activation. The present work was performed to further investigate the role of brain catecholamines and testicular blood flow in this pathway. The icv injection of 5 microl of 200 proof ethanol (EtOH; 86 micromol) did not result in detectable levels of the drug in the general circulation and did not induce neuronal damage, but rapidly blunted hCG-induced T release while not decreasing LH levels or altering testicular blood flow. EtOH significantly up-regulated transcripts of the immediate-early gene c-fos in the paraventricular nucleus (PVN) of the hypothalamus. Lesions of the PVN blocked the inhibitory effect of IL-1beta on T, but only partially interfered with the influence of EtOH. PVN catecholamine turnover significantly increased after icv injection of IL-1beta, but not EtOH. Brain catecholamine depletion due to the neurotoxin 6-hydroxydopamine did not alter the ability of hCG to induce T release, but significantly reversed the inhibitory effect of icv EtOH or IL-1beta on this response. Collectively, these results indicate that icv-injected IL-1beta or EtOH blunts hCG-induced T secretion through a catecholamine-mediated mechanism that does not depend on either peripherally mediated effects or pituitary LH, and that the PVN plays a role in these effects.

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).…”

Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists

“…This result is of interest as this timing indicates that testosterone is being elevated by mechanisms other that the classical hypothalamus-pituitary-gonadal axis where the endocrine response has been reported to have lag phase of *40 min from stimulus to increased concentration of testosterone (Spratt et al 1988). Recent research in vivo (Selvage et al 2004) has identified direct neural links between the para-ventricular nucleus of the hypothalamus and the testes, and this adds further supports to the idea that the rapid increase in testosterone seen here could have been elicited via a direct neural pathway.…”

Systemic Administration of Alcohol to Adult Rats Inhibits Leydig Cell Activity: Time Course of Effect and Role of Nitric Oxide

“…This influence is exerted via a neural brain-testicular pathway (Gerendai et al, 2000;Lee et al, 2002) whose activation by stress-like signals in the central nervous system (CNS) blunts Leydig cell responsiveness to LH-like agents such as human chorionic gonadotropin (hCG). While the mechanisms mediating the influence of this pathway on Leydig cell activity are not fully elucidated, we have shown that they involve CNS catecholamines and the paraventricular nucleus of the hypothalamus (Selvage et al, 2004b). Importantly, this pathway is completely independent of the pituitary (Ogilvie and Rivier, 1998;Rivier, 1999;Selvage and Rivier, 2003;Turnbull and Rivier, 1997).…”

“…While the respective importance of these different mechanisms remains the object of intense research, the use of alcohol as a model of stress presents one distinct advantage: namely, that alcohol can inhibit Leydig cell function following its intracerebroventricular (i.c.v. ) injection at doses that do not reach the periphery and do not induce neuronal damage in the brain (Selvage et al, 2004a(Selvage et al, , 2004b. This influence is exerted via a neural brain-testicular pathway (Gerendai et al, 2000;Lee et al, 2002) whose activation by stress-like signals in the central nervous system (CNS) blunts Leydig cell responsiveness to LH-like agents such as human chorionic gonadotropin (hCG).…”