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The role of kisspeptin in the pituitary has been debated, with conflicting results obtained in vitro on primary pituitary cell cultures. Some groups have seen no effect of kisspeptin on rat anterior pituitary cells (Matsui et al., 2004), whereas another group showed increased Ca2+ in 10% of cells, along with stimulation of LH and Growth Hormone (GH) (Gutierrez-Pascual et al., 2007). However, the doses used in this study were extremely high compared to other studies and the effects may be due to activation of other RFamide receptors.
LHβ expressing cells within rat pituitary explants expressed KiSS-1 mRNA; however KiSS-1 mRNA was also detected in other pituitary cells, possibly somatotropes. Gpr-54 mRNA was located in a subset of these LHβ expressing cells, suggesting the machinery is present for kisspeptin to have direct pituitary effects. Pituitary KiSS-1 mRNA appears to be regulated by estrogen and gpr-54 appears to be regulated by GnRH, making it plausible for direct effects to occur in the rat (Richard et al., 2008). However, all of these studies have used highly sensitive PCR techniques that do not reveal a functionally significant expression of gpr-54 and kisspeptin. Moreover, pharmacological doses of kisspeptin were required to elicit effects on the pituitary.
In ovine anterior pituitary cells, gpr-54 mRNA is present in gonadotropes, somatotropes and lactotropes. Administering kisspeptin to these cells when taken during the follicular phase causes an 80% increase in LH release. However, anterior pituitary cells taken from all other stages of the ovine cycle did not respond to kisspeptin administration. Also, in ovariectomised (OVX) ewes which were hypothalamic-pituitary disconnected (hence ablating effects of GnRH on the pituitary); no stimulation of LH by kisspeptin was seen at any time during the cycle (Smith et al., 2008). Furthermore, although kisspeptin is present at low levels in the hypophysial blood, this was not affected by estrogen, even at LH surge levels (Smith et al., 2008). Thus in vivo findings in contrast to in vitro findings indicate that direct pituitary effects of kisspeptin are not important for LH release. Overall, there is no convincing data demonstrating that direct effects of kisspeptin at the level of the pituitary is important for regulation of the HPG axis.
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