Effect of Kisspeptin on the Hypothalamic-Pituitary-Gonadal Axis of the Mare

Abstract

Kisspeptin, a neuropeptide product of the KiSS-1 gene, has recently been shown to control the timing and release of gonadotropin releasing hormone (GnRH) from the hypothalamus in laboratory animals and move anestrus ewes to normal cyclicity. This study was designed to determine whether kisspeptin would increase plasma luteinizing hormone (LH) in mares and whether kisspeptin could induce the anestrous mare to become cyclic. Six light horse mares were confirmed to be in mid-diestrus via teasing, rectal palpation and progesterone testing. Mares were then divided into three groups of two mares each and were treated with an intravenous (iv) injection of kisspeptin (1.0 nmol/kg or 0.5 nmol/kg) or saline. Mares responded to the kisspeptin treatment with a marked rise in LH concentration (P<0.05), and both doses achieved a similar response. The procedure was then repeated using the same protocol with reduced doses, and treatment groups were as follows: saline or kisspeptin (0.10 nmol/kg or 0.05 nmol/kg). There was a difference in the responses from the second experiment, with both treatments exhibiting inconsistent results. In order to determine whether kisspeptin could induce cyclicity in anestrus mares, six mares (n=3 per group) were infused for 20 hours with either saline or kisspeptin [100 µg/hr iv (77 nmol/hr)]. There was no effect of kisspeptin on plasma LH or on ovulation. These data suggest that mares, unlike ewes, may be unable to respond to kisspeptin during seasonal anestrus. Thus, a bolus iv treatment (0.5 nmol/kg) of kisspeptin or saline was administered to five seasonally acyclic mares in a cross-over design. Acyclic mares responded to iv kisspeptin with a rise in plasma LH (P<0.05), but despite a 7-fold increase, this level failed to exceed 1 mg/ml. These data suggest a regulatory role for kisspeptin in cyclicity and seasonality of horses, but suggest that effects in long-day breeders like the mare differ from those in short-day breeders like the ewe.