Biological and anatomical evidence for kisspeptin regulation of the hypothalamic-pituitary-gonadal axis of estrous horse mares

Endocrinology. 2009 Jun;150(6):2813-21. doi: 10.1210/en.2008-1698. Epub 2009 Feb 19.


The purpose of the present study was to evaluate the effects of kisspeptin (KiSS) on LH and FSH secretion in the seasonally estrous mare and to examine the distribution and connectivity of GnRH and KiSS neurons in the equine preoptic area (POA) and hypothalamus. The diestrous mare has a threshold serum gonadotropin response to iv rodent KiSS decapeptide (rKP-10) administration between 1.0 and 500 microg. Administration of 500 microg and 1.0 mg rKP-10 elicited peak, mean, and area under the curve LH and FSH responses indistinguishable to that of 25 microg GnRH iv, although a single iv injection of 1.0 mg rKP-10 was insufficient to induce ovulation in the estrous mare. GnRH and KiSS-immunoreactive (ir) cells were identified in the POA and hypothalamus of the diestrous mare. In addition, KiSS-ir fibers were identified in close association with 33.7% of GnRH-ir soma, suggesting a direct action of KiSS on GnRH neurons in the mare. In conclusion, we are the first to reveal a physiological role for KiSS in the diestrous mare with direct anatomic evidence by demonstrating a threshold-like gonadotropin response to KiSS administration and characterizing KiSS and GnRH-ir in the POA and hypothalamus of the diestrous horse mare.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estrous Cycle / drug effects
  • Estrous Cycle / physiology*
  • Female
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / metabolism
  • Horses / physiology*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology*
  • Hypothalamus / cytology
  • Hypothalamus / metabolism
  • Injections, Intravenous
  • Kisspeptins
  • Luteinizing Hormone / blood
  • Models, Animal
  • Neurons / metabolism
  • Oligopeptides / administration & dosage
  • Oligopeptides / physiology*
  • Ovary / drug effects
  • Ovary / physiology*
  • Ovulation / drug effects
  • Preoptic Area / cytology
  • Preoptic Area / metabolism
  • Reproduction / physiology
  • Tumor Suppressor Proteins / metabolism*


  • KISS1 protein, human
  • Kisspeptins
  • Oligopeptides
  • Tumor Suppressor Proteins
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone