Molecular Characterization and Estrogen Regulation of Hypothalamic KISS1 Gene in the Pig1

Abstract

Kisspeptin-GPR54 signaling plays an essential role in normal reproduction in mammals via stimulation of gonadotropin secretion. Here, we cloned the porcine KISS1 cDNA from the hypothalamic tissue and investigated the effect of estrogen on the distribution and numbers of KISS1 mRNA-expressing cells in the porcine hypothalamus. The full length of the cDNA was 857 bp encoding the kisspeptin of 54 amino acids, with the C-terminal active motif designated kisspeptin-10 being identical to that of mouse, rat, cattle, and sheep. In situ hybridization analysis revealed that KISS1-positive cell populations were mainly distributed in the hypothalamic periventricular nucleus (PeN) and arcuate nucleus (ARC). KISS1 expression in the PeN of ovariectomized (OVX) pigs was significantly upregulated by estradiol benzoate (EB) treatment. On the other hand, KISS1-expressing cells were abundantly distributed throughout the ARC in both OVX and OVX with EB animals. The number of KISS1-expressing neurons was significantly lowered by EB treatment only in the most caudal part of the ARC, but other ARC populations were not affected. The present study thus suggests that the PeN kisspeptin neurons could be responsible for the estrogen positive feedback regulation to induce gonadotropin-releasing hormone/luteinizing hormone (GnRH/LH) surge in the pig. In addition, the caudal ARC kisspeptin neurons could be involved in the estrogen negative feedback regulation of GnRH/LH release. This is the first report of identification of porcine KISS1 gene and of estrogen regulation of KISS1 expression in the porcine brain, which may be helpful for better understanding of the role of kisspeptin in reproduction of the pig.

Kisspeptin neurons mediate reflex ovulation in the musk shrew ( Suncus murinus )

“…sKp-29 showed a potent stimulatory effect on presumed ovulation, but sKp-40 had no effect on ovulation, indicating that sKp-29 is an endogenous kisspeptin in the musk shrew. Interestingly, suncus kisspeptin is much shorter than reported in other mammals, in which kisspeptin consists of 52-54 amino acids (9,17,24). Indeed, exogenous administration of sKp-29 mimicked the mating stimulus to induce presumed ovulation, and the sKp-29-induced ovulation was blocked completely by pretreatment with a GnRH antagonist.…”

“…Accumulating evidence suggests that in many mammalian species the kisspeptin-GPR54 system plays a critical role in inducing gonadotropin secretion through stimulation of GnRH release (11)(12)(13)(14)(15)(16)(17). Kisspeptin neurons play a role in the generation of the surge mode of GnRH/LH release to mediate the estrogenpositive feedback effect and then ovulation (18)(19)(20)(21) as well as the pulsatile GnRH/LH release responsible for follicular maturation (22,23).…”

Molecular cloning and characterization of KISS1 promoter and effect of KISS1 gene mutations on litter size in the goat

“…The two SNP loci were in Hardy-Weinberg disequilibrium in the SN and GZ breeds (P < 0.05), which showed that the genotypic frequencies had been affected by selection, mutation or migration. So far, there have been some studies of the KISS1 gene as a candidate gene for reproductive traits in animals, which revealed that the KISS1 gene plays an important role in animal reproduction (Tomikawa et al, 2010). Huijbregts et al (2012) detected three SNPs (c.638insT, c.641C>G and c.645G>CA) in the 3ꞌ-UTR of the human KISS1 gene, and found that the c.645G>CA mutation was associated with central precocious puberty.…”

The roles of kisspeptin and gonadotropin inhibitory hormone in stress-induced reproductive disorders

“…Indeed, subsequent studies have shown that kisspeptin stimulates GnRH secretion via GPR54 on GnRH neurons [48][49][50]. The amino acid sequence of kisspeptin, especially the C-terminal 10-amino acid sequence, is well conserved in most mammals [51][52][53][54][55][56][57]. Hypothalamic kisspeptin neurons are mainly located in the anterior and posterior nuclei; i.e., the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) and arcuate nucleus (ARC) [55,56,[58][59][60][61][62][63][64].…”

“…The amino acid sequence of kisspeptin, especially the C-terminal 10-amino acid sequence, is well conserved in most mammals [51][52][53][54][55][56][57]. Hypothalamic kisspeptin neurons are mainly located in the anterior and posterior nuclei; i.e., the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) and arcuate nucleus (ARC) [55,56,[58][59][60][61][62][63][64]. Kiss1 mRNA expression in the AVPV/POA is increased in the afternoon during proestrus and is also upregulated by the administration of estrogen, whereas Kiss1 mRNA expression in the ARC is decreased by the administration of estrogen [61,63,[65][66][67].…”