The Physiological Role of Arcuate Kisspeptin Neurons in the Control of Reproductive Function in Female Rats

Abstract

Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity.

Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats

“…The striking amplification of the LH surge shown here provides evidence that KNDy neurons are the source of the endogenous -opioid tone that limits the LH surge on proestrous afternoon. It has been previously shown that a modest knockdown of kisspeptin expression in the arcuate nucleus of adult rats will inhibit pulsatile LH secretion and lengthen estrous cycles but have no effect on the LH surge (75). Consistent with our studies, injections of diphtheria toxin to ablate kisspeptin cells in genetically engineered adult mice results in acyclicity and infertility (76).…”

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

“…Gonadotropinreleasing hormone (GnRH) neurons have been shown to express GPR54 receptor (Parhar et al 2004), through which kisspeptins activate GnRH secretion (Messager et al 2005). In a recent study (Beale et al 2014), kisspeptin knockdown in the arcuate nucleus (ARC) has been reported to result in a decrease in luteinizing hormone (LH) pulse frequency, which suggests that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and estrous cyclicity. Kisspeptin (d'Anglemont de Tassigny et al 2007) or Gpr54 knockout mice (Messager et al 2005) are found to be infertile.…”

Diurnal regulation of hypothalamic kisspeptin is disrupted during mouse pregnancy

“…tonic control of gonadotropin secretion, as opposed to generating the preovulatory LH surge (Smith et al 2005b, Beale et al 2014. Diurnal rhythmicity in the SCN (as part of the anterior hypothalamus) during pregnancy remains intact, even though the expression of core clock genes (including Bmal1 and Rev-erbα) is altered during pregnancy compared with diestrus (Wharfe et al 2016).…”