Biological and Anatomical Evidence for Kisspeptin Regulation of the Hypothalamic-Pituitary-Gonadal Axis of Estrous Horse Mares

Abstract

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.

Acute Injection and Chronic Perfusion of Kisspeptin Elicit Gonadotropins Release but Fail to Trigger Ovulation in the Mare1

“…Whether such a difference in sequence translates into a difference in biological activity is unknown. However, we deem it unlikely since the characteristics of the response obtained by others with either rKp10 [44] or eKp10 [29] in light-horse mares appear similar and are also in good agreement with those we report here. Furthermore, the amplitude of the gonadotropin response to eKp10 is not overtly smaller than that to GnRH, albeit comparatively larger doses of eKp10 have to be used.…”

“…For instance, in the ovine the populations located within the POA/dbB and the medio-basal hypothalamus (MBH) represent 40-50% and 15-20% of GnRH neurons, respectively [49,50]. This is virtually opposite to the equine, where up to 60% of GnRH neurons are found within the MBH while the POA/dbB population comprises only about 10% of the total [44,51]. This anatomical difference may be functionally meaningful since Kp neurons located within the anterior hypothalamus appear to preferentially project onto GnRH cell bodies while Kp neurons of the Arc may act mostly on GnRH nerve terminals within the median eminence [1,2].…”

International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

“…Kisspeptin has been identified in homologous regions of the brain in monkey (Shahab et al, 2005; Ringel et al, 2002;Bilban et al, 2004;Irwig et al, 2004;Navarro et al, 2004a;Mead et al, 2007bMead et al, al., 2007Ramaswamy et al, 2008), sheep (Estrada et al, 2006Franceschini et al, 2006;, horse (Decourt et al, 2008;Magee et al, 2009), hamster (Paul et al, 2009), goat pig (Tomikawa et al, 2010). Kisspeptin has also been found to be expressed in frog and fish species (Biran et al, 2008;Felip et al, 2008;Kanda et al, 2008;van Aerle et al, 2008;Carrillo et al, 2009;Kitahashi et al, 2009;Li et al, 2009;Yang et al, 2010), suggesting that the kisspeptin system has been conserved during evolution.…”

Kisspeptin activates the hypothalamic–adenohypophyseal–gonadal axis in prepubertal ewe lambs

“…Although pubertal activation of pulsatile GNRH release has been well characterized (Wildt et al 1980, Kinder et al 1995, the mechanisms and neuronal pathways leading to increased frequency of GNRH release during the peripubertal period remain unclear. Kisspeptin, a peptide with potent stimulatory effects on the release of GNRH and LH (Matsui et al 2004, Messager et al 2005, Lents et al 2008, Magee et al 2009, Smith et al 2009b, plays a critical role. Kisspeptin (d'Anglemont de Tassigny et al 2007, Lapatto et al 2007) and its receptor (de Roux et al 2003, Seminara et al 2003 are essential for normal onset of puberty.…”