Hypothalamic expression of KISS1 and gonadotropin inhibitory hormone genes during the menstrual cycle of a non-human primate - PubMed (original) (raw)

Hypothalamic expression of KISS1 and gonadotropin inhibitory hormone genes during the menstrual cycle of a non-human primate

Jeremy T Smith et al. Biol Reprod. 2010 Oct.

Abstract

Kisspeptin, the product of the KISS1 gene, stimulates gonadotropin-releasing hormone (GnRH) secretion; gonadotropin inhibitory hormone (GnIH), encoded by the RF-amide-related peptide (RFRP) or NPVF gene, inhibits the reproductive axis. In sheep, kisspeptin neurons are found in the lateral preoptic area (POA) and the arcuate nucleus (ARC) and may be important for initiating the preovulatory GnRH/luteinizing hormone (LH) surge. GnIH cells are located in the ovine dorsomedial hypothalamic nucleus (DMN) and paraventricular nucleus (PVN), with similar distribution in the primate. KISS1 cells are found in the primate POA and ARC, but the function that kisspeptin and GnIH play in primates has not been elucidated. We examined KISS1 and NPVF mRNA throughout the menstrual cycle of a female primate, rhesus macaque (Macaca mulatta), using in situ hybridization. KISS1-expressing cells were found in the POA and ARC, and NPVF-expressing cells were located in the PVN/DMN. KISS1 expression in the caudal ARC and POA was higher in the late follicular phase of the cycle (just before the GnRH/LH surge) than in the luteal phase. NPVF expression was also higher in the late follicular phase. We ascertained whether kisspeptin and/or GnIH cells project to GnRH neurons in the primate. Close appositions of kisspeptin and GnIH fibers were found on GnRH neurons, with no change across the menstrual cycle. These data suggest a role for kisspeptin in the stimulation of GnRH cells before the preovulatory GnRH/LH surge in non-human primates. The role of GnIH is less clear, with paradoxical up-regulation of gene expression in the late follicular phase of the menstrual cycle.

PubMed Disclaimer

Figures

FIG. 1.

FIG. 1.

Schematic drawings of coronal sections through the rhesus macaque brain showing the location of KISS1 mRNA and NPVF mRNA (GnIH)-expressing cells (dots). Representative sections (modified from [45]) are 1 mm apart. Section serial numbers indicate the number of millimeters anterior (+) or posterior (−) from the complete anterior commissure (ac). A–C) Representative dark-field photomicrographs showing the distribution of KISS1 mRNA-expressing cells in the POA (A), bed nucleus of the stria terminalis (B), and ARC (C). D) Representative dark-field photomicrographs showing the distribution of NPVF mRNA-expressing cells in the PVN/DMN. 3V, third ventricle; oc, optic chiasm; ORe, optic recess; POP, preoptic periventricular nucleus; StT, bed nucleus of the stria terminalis. Bars = 200 μm.

FIG. 2.

FIG. 2.

Representative dark-field photomicrographs showing KISS1 mRNA-expressing cells (as reflected by the presence of white clusters of silver grains) in the POA and ARC from rhesus macaques at the luteal phase (A and D), early follicular phase (B and E), and late follicular phase (C and F). Quantification of KISS1 mRNA in the rostral, mid, and caudal ARC and the POA is shown. The number of KISS1 mRNA-positive cells per section was unchanged over the cycle, but the number of grains per KISS1 cell in the caudal ARC and POA was significantly greater in animals at the late follicular phase Values are presented as the mean ± SEM (n = 3–4 per group). 3V, third ventricle; ME, median eminence; ORe, optic recess. Bars = 200 μm. *P < 0.05, **P < 0.01.

FIG. 3.

FIG. 3.

Representative dark-field photomicrographs showing NPVF mRNA-expressing cells (GnIH; as reflected by the presence of white clusters of silver grains) in the PVN/DMN region from rhesus macaques at the luteal phase (A), early follicular phase (B), and late follicular phase (C). Quantification of NPVF mRNA shows the number of NPVF mRNA-positive cells per section was unchanged over the cycle, but the number of grains per NPVF cell was significantly reduced in luteal-phase animals. Values are presented as the mean ± SEM (n = 3–4 per group). 3V, third ventricle. Bars = 200 μm. *P < 0.05.

FIG. 4.

FIG. 4.

Z-stack apotome analysis showing putative input to GnRH neurons from kisspeptin and GnIH terminals. The images show examples of GnRH neurons (red) that have kisspeptin fibers (A) or GnIH fibers (B; green) in close apposition. The percentage of GnRH neurons with kisspeptin or GnIH appositions was similar over the menstrual cycle in the POA and MBH. Values are presented as the mean ± SEM (n = 3–4 per group). Bars = 20 μm.

FIG. 5.

FIG. 5.

Localization of GnIH-ir terminals in the median eminence of the rhesus macaque. Fluorescence photomicrographs show few GnIH fibers (green) located in the median eminence, where an abundance of GnRH fibers is noted (red). Arrows indicate GnIH fibers; arrowheads indicate GnRH neurons in the MBH. Box in A demonstrates the approximate position of photomicrographs B–D. 3V, third ventricle; ARC, arcuate nucleus; DMN, dorsomedial nucleus of the hypothalamus; LH, lateral hypothalamus; ME, median eminence; opt, optic tract; VMH, ventromedial hypothalamus. Bars = 100 μm.

Similar articles

Cited by

References

    1. Pau KY, Berria M, Hess DL, Spies HG.Preovulatory gonadotropin-releasing hormone surge in ovarian-intact rhesus macaques. Endocrinology 1993; 133: 1650–1656. - PubMed
    1. Shivers BD, Harlan RE, Morrell JI, Pfaff DW.Absence of estradiol concentration in cell nuclei of LHRH-immunoreactive neurones. Nature 1983; 304: 345–347. - PubMed
    1. Herbison AE, Theodosis DT.Localization of estrogen receptors in preoptic neurons containing neurotensin but not tyrosine hydroxylase, cholecystokinin or luteinizing hormone-releasing hormone in the male and female rat. Neuroscience 1992; 50: 283–298. - PubMed
    1. Skinner DC, Caraty A, Allingham R.Unmasking the progesterone receptor in the preoptic area and hypothalamus of the ewe: no colocalization with gonadotropin-releasing neurons. Endocrinology 2001; 142: 573–579. - PubMed
    1. Smith JT.Kisspeptin signaling in the brain: Steroid regulation in the rodent and ewe. Brain Res Rev 2007; 57: 288–298. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources