Kisspeptin Is Present in Ovine Hypophysial Portal Blood But Does Not Increase during the Preovulatory Luteinizing Hormone Surge: Evidence that Gonadotropes Are Not Direct Targets of Kisspeptin in Vivo

Abstract

There is strong evidence that kisspeptin acts to regulate GnRH secretion, but whether there is also a component of action on the gonadotropes is not clear. Using quantitative RT-PCR, we found that G protein-coupled receptor-54 mRNA is expressed in ovine pituitary cell fractions enriched for gonadotropes as well as in somatotropes and lactotropes. To test whether kisspeptin acts directly on the pituitary gonadotropes, we first examined LH release from primary ovine pituitary cell cultures treated with kisspeptin. We found that kisspeptin treatment increased the concentration of LH in culture media by 80%, compared with control, but only in pituitary cultures from ewes during the follicular phase of the estrous cycle. After this, we determined whether kisspeptin acts on the pituitary gland in vivo. Using GnRH-replaced ovariectomized hypothalamo-pituitary-disconnected ewes, we were not able to achieve any effect of kisspeptin on LH under steady-state conditions or during the period of an estrogen-induced LH surge. Finally, we collected hypophysial portal blood samples from ovariectomized ewes and measured kisspeptin levels. Low but detectable amounts of kisspeptin were found in portal plasma, but levels were similar in ovariectomized ewes that were untreated or given estrogen to elicit an LH surge. Thus, although we observed an effect of kisspeptin on LH release in vitro in some situations, similar findings were not obtained in vivo. Moreover, the low concentrations of kisspeptin in hypophysial portal blood and the lack of any change during the period of an estrogen-induced GnRH/LH surge suggest that action on the pituitary gland is not of major consequence in terms of LH release.

Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity

“…In support of this hypothesis, both kiss and GPR54 are expressed in the pituitary of several species investigated to date (Richard et al, 2009); GPR54 has also been detected in ovine cellular fractions enriched of gonadotropes, somatotropes and lactotropes (Smith et al, 2008b). Once again, this duality suggested in many species is not the rule, since in a sheep model of hypothalamo-pituitary disconnection, kisspeptin loses its stimulatory action on LH secretion, thus assuming an exclusive effect upstream of the pituitary (Smith et al 2008b). Anyway, this debate is still open and surely warrants further investigations.…”

“…Hence, indicative results as the presence of a functional kisspeptin receptor in the pituitary, combined with the finding that kisspeptin is released in hypophyseal portal blood, reinforce the idea that kisspeptin could be able of a dual action at both the hypothalamus and pituitary level. In support of this hypothesis, both kiss and GPR54 are expressed in the pituitary of several species investigated to date (Richard et al, 2009); GPR54 has also been detected in ovine cellular fractions enriched of gonadotropes, somatotropes and lactotropes (Smith et al, 2008b). Once again, this duality suggested in many species is not the rule, since in a sheep model of hypothalamo-pituitary disconnection, kisspeptin loses its stimulatory action on LH secretion, thus assuming an exclusive effect upstream of the pituitary (Smith et al 2008b).…”

Mystic Effects of Kisspeptin in Reproduction of Livestock

“…Additionally, Kp-IR fibers were found to encompass from the ARC into the external neurosecretory segment of the Median Eminence (ME) (Pompolo et al, 2006) in both females (ewes: Smith et al 2011) and males (goat: Ohkura et al, 2009b). These terminals might be the basis for the kisspeptin that has been documented in the ewe hypophyseal portal blood (Smith et al, 2008). Kisspeptin might have a non-synaptic action at the ME level to initiate GnRH release.…”

“…2009). Captivatingly, the estrogen hold on Kiss1 mRNA and kisspeptin protein expression within the ARC were superior throughout the non-breeding season in ewes (Smith et al, 2008). Hence, the core candidate to facilitate changes in feedback effect of estrogen seems to be Kisspeptin cells (Smith, 2009).…”

Rola sygnalizacji kisspeptyny w osi podwzgórze–przysadka–nadnercza — aktualna perspektywa

“…It has been shown from animal studies revealing expression of genes related to kisspeptin and its receptor in gonadotrophs [51], secretion of FSH and LH from kisspeptin treated pituitary explants [52,53], and the presence of kisspeptin in the hypophyseal portal system [54]. It has been further explained that although kisspeptin may directly stimulate the pituitary gland, the evidence is more in favour of indirect stimulation of gonadotrophs by increasing GnRH secretion as the principal physiological pathway [1].…”