Colocalization of Kisspeptin and Gonadotropin-Releasing Hormone in the Ovine Brain

Abstract

Kisspeptin is a peptide that has been implicated in the regulation of GnRH cells in the brain. Immunohistochemical studies were undertaken to examine the distribution of kisspeptin-immunoreactive (IR) cells in the ovine diencephalon and determine the effect of ovariectomy in the ewe. We report that kisspeptin colocalizes to a high proportion of GnRH-IR cells in the preoptic area, which is a novel finding. A high level of colocalization of kisspeptin and GnRH was also seen in varicose neuronal fibers within the external, neurosecretory zone of the median eminence. Apart from the kisspeptin/GnRH cells, a population of single-labeling kisspeptin-IR cells was also observed in the preoptic area. Within the hypothalamus, kisspeptin-IR cells were found predominantly in the arcuate nucleus, and there was an increase in the number of immunohistochemically identified cell within this nucleus after ovariectomy. Kisspeptin-IR cells were also found in the periventricular nucleus of the hypothalamus, but the number observed was similar in gonad-intact and ovariectomized ewes. The colocalization of GnRH and kisspeptin within cells of the preoptic area and GnRH neurosecretory terminals of the median eminence suggests that the two peptides might be cosecreted into the hypophyseal portal blood to act on the pituitary gland. Effects of ovariectomy on the non-GnRH, Kisspeptin-IR cells of the hypothalamus suggest that kisspeptin production is negatively regulated by ovarian steroids.

Neurochemical Characterization and Sexual Dimorphism of Projections from the Brain to Abdominal and Subcutaneous White Adipose Tissue in the Rat

“…The relative proportions of neurons projecting to retroperitoneal WAT (rWAT) and/or subcutaneous (inguinal) WAT (iWAT) and immunohistochemical data, represented as the mean percentage of total PRV-positive neurons, were transformed for analysis using the arcsin transformation (Sokal and Rohlf, 1969;Pompolo et al, 2006). Data that did not fit a normal distribution determined by the Shapiro-Wilk test for normality ( p Ͻ 0.05) and/or violated the homogeneity of variance assumption determined by the Levene's test of equality of variances ( p Ͻ 0.05) were analyzed using nonparametric statistics.…”

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

“…Gonadectomized mice, sheep, and rhesus monkeys show increased Kiss1 mRNA expression in the arcuate nucleus or infundibular region (Irwig et al, 2004;Navarro et al, 2004a;Pompolo et al, 2006Smith et al, 2005aRometo et al, 2007Shibata et al, 2007. Sex steroid replacement decreases the elevated Kiss1 mRNA expression to control levels (Navarro et al, 2004a;Smith et al, 2005bPompolo et al, 2006;Rometo et al, 2007;Shibata et al, 2007), suggesting that this circuitry represents negative feedback control of gonadotropin secretion. Conversely, the preovulatory LH surge involves positive feedback; in mice and rats, this seems to be regulated by neurons in the AVPV (Smith et al, 2005a(Smith et al, , 2006bAdachi et al, 2007).…”

“…This seems to be mediated by the estrogen receptor ER␣ (Kinoshita et al, 2005;Adachi et al, 2007;Roa et al, 2008b,c). However, this mechanism of control varies between species; in sheep and primates, kisspeptin neurons are restricted to the arcuate nucleus and the preoptic area, and both positive and negative feedback regulation of gonadotropin secretion seems to occur in the arcuate nucleus Pompolo et al, 2006;.…”

Current and future applications of GnRH, kisspeptin and neurokinin B analogues

“…This anatomically-linked functional dimorphism of KP neurons is not evident in sheep and monkeys as both types of neurons appear to be localized in the ARC 91,97,98 .…”