Expression Studies

Kisspeptin and GPR54 are widely expressed in human tissues.15,16,18 It was demonstrated by RT-PCR that KISS1 mRNA is expressed mainly in the placenta, but also in the brain, including the hypothalamus, basal ganglia, pituitary, and peripheral organs, such as pancreas, testis and, in lower levels, in the liver and small intestine.15,16,18 GPR54 transcripts were particularly abundant in placenta, brain, pituitary, spinal cord, and pancreas, whereas lower levels were detected in other tissues, including lymphocytes, spleen, testis, and adipose tissue.15,16,18

In situ hybridization study of the mouse and the rat brains, showed that expression of KISS1 was highest in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei, known to send projections to the medial preoptic area, where there is an abundance of GnRH cell bodies.60 Moreover, it was demonstrated that GnRH neurons coexpress gpr54 transcripts.60 Hypo-thalamic kiss1 and gpr54 mRNA expression increases progressively across the pubertal development, reaching maximum levels at the beginning of puberty in rodents and primates.47,51 In male and female rodents, hypothalamic kiss1 mRNA expression increased dramatically after bilateral gonadectomy in adult animals and returned to the anterior levels after sexual steroids replacement as demonstrated by immunohistochemistry and in situ hybridization, suggesting an inhibitory effect for the sex steroids.47 In the AVPV, however, kiss1 expression was decreased after gonadectomy and increased after sex steroid replacement, in a positive feedback pattern.60,61 Moreover, whereas the overall distribution of kisspeptin immunoreactivity was very similar between males and females, the number of cell bodies expressing kisspeptin in the AVPV is over 10-fold higher in the female.62 Interestingly, the AVPV is one of the only sexually dimorphic areas in the rodent brain that is larger in the female than the male.6 Virtually, all kisspeptin neurons in the ARC and the AVPV were shown to coexpress the estrogen receptor-a (ER-a), whereas only 25-30% of these neurons express the ER-b. Furthermore, ER-b knockout ovariectomized female mice respond to estradiol administration in the same way as the wildtype animals, showing that the estradiol effects are mediated by the ER-a. In males, testosterone effects are mediated by the androgen receptor as well as the ER-a, after testosterone aromatization in estradiol in the ARC. However, in the AVPV, testosterone-induced kiss1 transcription seems to be mediated exclusively via ER-a. The ARC is known to control the negative feedback regulation of GnRH and gonadotropin secretion, whereas the estrogen-induced kisspeptin increase in the AVPV seems to be involved in the positive feedback regulation which leads to the preovulatory LH surge in females.60,63

In addition to the hypothalamic nuclei, it was recently demonstrated by immunohistochemistry that kisspeptin and GPR54 are coexpressed by the gonadotrophs, suggesting the possibility of an autocrine or paracrine action of kisspeptin in the pituitary.64 However, in vitro studies assessing the direct stimulatory effects of kisspeptins on gonadotropin secretion in the pituitary have given conflicting results.65 Gutierrez-Pascual et al.66 demonstrated that kisspeptin-10 induced a rise in free cytosolic calcium concentration in approximately 10% of male rat pituitary cells, including not only gonadotrophs, but also somatotrophs.

Was this article helpful?

0 0

Post a comment