Role of the hypothalamus in ghrelin effects on reproduction: sperm function and sexual behavior in male mice

Abstract

Ghrelin (GHRL) is an orexigenic peptide that has been investigated as one of the signals responsible for reproductive performance of mammals under fluctuating metabolic conditions. Central GHRL administration impairs spermatogenesis in mice by regulating the hypothalamic–pituitary–gonadal axis function. In the present study the hypothalamus role as a mediator of GHRL effects on sperm fertilizing capacity and male sexual behavior was evaluated. After 42 days of hypothalamic GHRL infusion or artificial cerebrospinal fluid, in vitro and in vivo sperm fertilizing capacity, testicular α-tubulin, speriolin gene expression and spermatic α-tubulin protein were evaluated. Hypothalamic expression of genes Kiss1, GPR54 and GnRH were also studied. A second group of animals were infused with one time only into the hypothalamus to evaluate the effects on sexual behavior. Results demonstrated that chronic GHRL administration to male mice significantly increased the percentages of pre-implantation embryo loss and the number of post-implantation embryo loss. In relation to the gene expression, our results show a relative decrease of Kiss1, GPR54 and Spatc1. Although no significant differences were observed in the quantitative expression of α-tubulin protein, qualitative changes in its expression pattern were observed. In addition, a dual effect on sexual behavior was observed: 40% of the treated animals showed a significant reduction in the number of mounts and intromissions, while a 60% showed a significant decrease in ejaculation latency vs. control animals. In conclusion, our results provide evidence that central GHRL administration possibly induces failure in embryo development and/or implantation in the females mated with treated males, possibly because of a negative effect in the α-tubulin pattern.

Olfactory and neuropeptide inputs to appetite neurons in the arcuate nucleus

“…Both rabies and Pseudorabies viruses infected neurons directly upstream of AgRP and POMC neurons in numerous brain areas 13,14 . Many of these are in the hypothalamus, which regulates a large variety of physiological and behavioral functions including reproduction [17][18][19][20] , appetite control [21][22][23] and stress [24][25][26][27] . If one could determine neuromodulators used by different upstream neurons to modulate appetite, one would have molecular/genetic tools to explore the impact of different upstream areas on AgRP or POMC neurons.…”