Neuropeptide Y acts within the rat testis to inhibit testosterone secretion

Abstract

The factors that influence Leydig cell activity currently include peptides such as neuropeptide Y (NPY). In this work we investigated the ability of this compound, injected directly into the testes of adult male rats, to alter testosterone (T) release into the general circulation. At a 5 μg/kg dose administered 1 h prior to challenge with human chorionic gonadotropin (hCG, 1.0 U/kg, iv), NPY significantly (P<0.01) blunted the T response to this gonadotropin. The inhibitory effect of NPY was observed in animals pretreated with an antagonist to gonadotropin-releasing hormone or not, indicating that the decrease in plasma T found was most likely independent of pituitary luteinizing hormone. However, testicular levels of steroidogenic acute regulatory (STAR) protein or translocator protein (TSPO) in the Leydig cells did not exhibit consistent changes, which suggested that other mechanisms mediated the blunted T response to hCG. We therefore used autoradiography and immunohistochemistry methodologies to identify NPY receptors in the testes, and found them primarily located on blood vessels. Competition studies further identified these receptors as being Y 1 , a subtype previously reported to modulate the vasoconstrictor effect of NPY. The absence of significant changes in STAR and TSPO levels, as well as the absence of Y 1 receptors on Leydig cells, suggest that NPY-induced decreases in T release is unlikely to represent a direct effect of NPY on these cells. Rather, the very high expression levels of Y 1 found in testicular vessels supports the concept that NPY may alter gonadal activity, at least in part, through local vascular impairment of gonadotropin delivery to, and/or blunted T secretion from, Leydig cells.

Neuropeptide Y and orexin immunoreactivity in the sparrow brain coincide with seasonal changes in energy balance and steroids

“…Natural shifts in energy balance are associated with reproduction. Orexigenic neuropeptides generally suppress the reproductive axis by lowering gonadotropin‐releasing hormone (GnRH) neuronal activity (Gaskins & Moenter, ); decreasing luteinizing hormone release (Furuta, Mitsushima, Shinohara, Kimura, & Funabashi, ); and reducing vascularization of the gonads (Allen et al, ). There are also potential effects of gonadal NPY in the regulation of steroidogenesis (Priyadarshini & Lal, , ).…”

Predictive value of combined analysis of pro‐NPY and ERG in localized prostate cancer

“…NPY and pro‐NPY have been found associated with development of different endocrine‐related cancers , including neural crest‐derived tumors , breast cancer , ovarian cancer and PCa . Even though studies have failed to observe significant changes in proliferation of PCa cells in response to NPY stimulation , it has been suggested that NPY regulate the tumor microenvironment and have a systemic effect on androgen levels . Furthermore, proteome profiling of tumor tissue and plasma from PCa patients has identified pro‐NPY as a potential biomarker for PCa aggressiveness .…”

The neuropeptide orexin A – search for its possible role in regulation of steroidogenesis in adult mice testes

“…OX1R antagonist (SB‐334867) was injected directly into the testis using a sterile infant transfusion needle held with the right hand. Preliminary studies conducted with Evans Blue indicated that this protocol was consistent with wide spread disbursement of the injection volumes (Allen et al ., ).…”

“…Doses of the antagonist were selected based on the study of Allen et al . (), where neuropeptide Y at a dose of 5 μg/kg was injected directly into rat testis to see its effect on T production. In our study, 2, 4, 8, 12 and 16 μg of SB‐334867 were injected directly into mice testis to see the effect of the antagonist on testicular steroidogenesis and spermatogenesis at 6, 12, 24, 48 and 72 h post‐treatment.…”