Early Development of Hypothalamic Neurons Expressing Proopiomelanocortin Peptides, Neuropeptide Y, and Kisspeptin in Fetal Rhesus Macaques.

We have documented the early embryonic development of hypothalamic neurons expressing β-endorphin, α-melanocyte-stimulating hormone, neuropeptide Y, and kisspeptin in rhesus macaques, an animal model that is very similar to humans. Neurons expressing both β-End and αMSH are the first to develop and are initially located in the lateral basal hypothalamus (LBH) as early as day 32-34 of gestation. By day 45 of gestation, these neurons have migrated into the medial basal hypothalamic (MBH) area as their final destination. NPY neurons within the ARH develop later and first appear at day 44 of fetal life, at which time a cluster of neurons is present within the ARH-MBH area. NPY neurons continue to be expressed within the ARH area at all of the later fetal ages analyzed. Similarly, kisspeptin neurons develop later compared with β-End, although only a few cells are present in the ARH by day 44 of gestation, at which time kisspeptin is also expressed in the developing anterior lobe of the pituitary. By day 70 of gestation, the rostral to caudal distribution and cell size of Kiss1 neurons within the MBH are similar in females and males. In addition, Kiss1 fibers are also expressed in the POA by day 70. By day 130 of gestation, Kiss1 neurons exhibit a wider dorsal and lateral distribution within the MBH, with highly increased fiber distribution. Therefore, the development of these neurons is much earlier than what had been described previously for αMSH and NPY in primates.