Presence of Corticotrophin‐Releasing Factor and /or Tyrosine Hydroxylase in Cells of a Neural Brain‐Testicular Pathway That are Labelled by a Transganglionic Tracer

Abstract

Our laboratory has shown that male testosterone levels are not solely controlled by the release of hypothalamic gonadotrophin-releasing hormone and pituitary luteinising hormone, but are also regulated by a multisynaptic pathway connecting the brain and the testis that interferes with the testosterone response to gonadotrophins. This pathway, which is independent of the pituitary gland, is activated by an i.c.v. injection of either the stress-related peptide corticotrophin-releasing factor (CRF) or of beta-adrenoceptor agonists, both of which alter androgen release and decrease levels of the peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein within Leydig cells. Our original studies used the retrograde transganglionic tracer pseudorabies virus (PRV) to map progression of the virus from the testes to upper brain levels. The present study aimed to extend this work by identifying the regions where CRF and catecholamine neurones represented components of the stress-activated, brain-testicular pathway that prevents testosterone increases. To this end, anaesthetised adult male rats received an intra-testicular injection of PRV. Using immunofluorescence, we identified co-labelling of PRV and either CRF or tyrosine hydroxylase (TH), the enzyme responsible for biogenic amine synthesis. Co-labelling of PRV and CRF was found in the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus (PVN) and the central amygdala. Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kölliker-Fuse area, area of A5, locus coeruleus, nucleus of solitary tract, area of C3, area of C2 and the area of C1/A1. These results indicate that most cell groups of the ventral noradrenergic pathway have neurones that are a part of the brain-testicular pathway. This suggests that the stress hormones CRF and catecholamines may act as neurotransmitters that signal the pathway to inhibit increases in plasma testosterone levels.

Testosterone replacement does not normalize carcass composition in chronically decerebrate male rats

“…The neuroanatomical basis for the neural control of the testes has been illustrated using the pseudorabies virus multisynaptic tract tracing method. Specifically, with this method, brain sites across the neural axis serving as components of the autonomic outflow circuit from brain to the testes have been revealed, including forebrain areas that would be disconnected by decerebration (13,24,27,39). Thus, the decreased serum testosterone concentrations could involve decerebration-induced distal sympathetic denervation of the testes, because proximal denervation of the testes severely impairs testosterone synthesis/release (6,31).…”

“…More specifically, the release of LHRH appears to be modulated by ascending noradrenergic projections from the locus coeruleus to the medial preoptic area and median eminence (30,37,43), although contradictory evidence suggests that castration does not increase the noradrenergic tone to the LHRH system (e.g., 28,29) questioning this as the possible mechanism underlying the lack of increased LH in CD rats with low serum testosterone concentrations. Alternatively, there is accumulating evidence that testicular function can be modulated independently of the traditional hypothalamo-pituitary-gonadal axis, especially under stressful conditions (22,24,27,38,39). The neuroanatomical basis for the neural control of the testes has been illustrated using the pseudorabies virus multisynaptic tract tracing method.…”

Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

“…27 Thus, in NAcc and striatum, the reinforcing effect of nicotine and other psychostimulants is characterized by increasing DA transmission that binds to the DA Rs, which can further induce DA R downregulation. 6,7,30,31 James et al 23 proved the existence of direct brain-testis pathway that controls testicular function using retrograde viral tracing from the testicular TH expressing nerve fibers to the midbrain DAergic area. The presence of DA and DAergic marker, TH, in different testicular tissues further establish the paracrine action of DA in spermatogenesis.…”

“…CA, especially DA, and TH, the DA marker, are found to be important modulators of testis volume, seminiferous epithelium maturation, and spermatogenesis as well as testosterone production. 23,26 DA, BDNF, and oxidative stress also have a potential role in structure-function impairment and total antioxidant depletion in the testicular tissues. 36,82,83 Nicotine further binds with the Rs, hormones, enzymes, etc.…”

“…22,23 TH, the rate-limiting enzyme of DA (CA) synthesis, is found in Leydig cells, germinal cells, neuron-like cells, and nerve fibers, 24,25 and DA-R is located in neuron-like cells and nerve fibers in human testicular tissue, 24 suggesting paracrine actions of DA in the spermatogenic process. 26 Further, testosterone plays a crucial role in regulation of neural structure and function, modulation of brain circuits at puberty, and regulation of social, risk-taking, and cognitive behavior.…”