The Decline in Pulsatile GnRH Release, as Reflected by Circulating LH Concentrations, During the Infant-Juvenile Transition in the Agonadal Male Rhesus Monkey (Macaca mulatta) Is Associated With a Reduction in Kisspeptin Content of KNDy Neurons of the Arcuate Nucleus in the Hypothalamus

Abstract

Puberty in primates is timed by 2 hypothalamic events: during late infancy a decline in pulsatile GnRH release occurs, leading to a hypogonadotropic state that maintains quiescence of the prepubertal gonad; and in late juvenile development, pulsatile GnRH release is reactivated and puberty initiated, a phase of development that is dependent on kisspeptin signaling. In the present study, we determined whether the arrest of GnRH pulsatility in infancy was associated with a change in kisspeptin expression in the mediobasal hypothalamus (MBH). Kisspeptin was determined using immunohistochemistry in coronal hypothalamic sections from agonadal male rhesus monkeys during early infancy when GnRH release as reflected by circulating LH concentrations was robust and compared with that in juveniles in which GnRH pulsatility was arrested. The distribution of immunopositive kisspeptin neurons in the arcuate nucleus of the MBH of infants was similar to that previously reported for adults. Kisspeptin cell body number was greater in infants compared with juveniles, and at the middle to posterior level of the arcuate nucleus, this developmental difference was statistically significant. Neurokinin B in the MBH exhibited a similar distribution to that of kisspeptin and was colocalized with kisspeptin in approximately 60% of kisspeptin perikarya at both developmental stages. Intensity of GnRH fiber staining in the median eminence was robust at both stages. These findings indicate that the switch that shuts off pulsatile GnRH release during infancy and that guarantees the subsequent quiescence of the prepubertal gonad involves a reduction in a stimulatory kisspeptin tone to the GnRH neuronal network.

Neuroendocrine control of the onset of puberty

“…This view is supported by the report in the juvenile female monkey that release into the median eminence of kisspeptin, the posited output of the GnRH pulse generator, occurs at a greatly reduced amplitude when compared to the adult [51]. Also consistent with this view is the finding from this laboratory that in the male rhesus monkey the number of neurons in the arcuate nucleus expressing kisspeptin is reduced in association with the transition from the infantile to juvenile stage of development [61]. Similarly, expression of KISS1 , the gene that encodes for kisspeptin increases in the arcuate nucleus of male and female monkeys in association with the transition from the juvenile to pubertal stage of development [62].…”

Menstrual Bleeding as a Manifestation of Mini-Puberty of Infancy in Severe Prematurity

“…13 Less is known about the transition of the HPG axis from an active state during mini-puberty to quiescence during prepubertal years, although there is evidence that kisspeptin signaling is also involved. 14 …”

Puberty in Mice and Rats

“…Rodents, especially rats and mice, have been very useful animal models in which to study this developmental process, vital to the survival of mammalian species, and, as indicated by the occurrence of the GnRH peptide and its hypophysiotropic role in all vertebrates (reviewed in Refs 5,113), evolutionarily conserved. Mice and rats thus have not been considered appropriate animal models in which to investigate the mechanisms underlying this quiescent period of relative hypogonadotropism, which is clearly evident in agonadal primates, including man [116][117][118] (see also Chapter 32). This group includes primates, whose use is restricted by their size, cost, and limited reproductive capacity.…”