Endocrine Abstracts

The development and maturation of kisspeptin neurons is critical for activating GnRH release needed to initiate puberty. However, little is known of the development and organization of kisspeptin neurons in the human hypothalamus and the anatomical architecture of kisspeptin neurons in rodents is distinct from that of primates.

The aim of the present study was to examine the development of the hypothalamic neuroendocrine circuitry that sets the structural basis for GnRH secretion during sexual differentiation, puberty and adulthood. We analyzed the expression of neuroendocrine genes relevant to reproduction (KISS1, GPR54, GNRH1, TAC3, and TAC3R) in late stages of human embryonic development by Taqman quantitative reverse-transcription PCR. We also used immunocytochemistry multiple labelling techniques to examine the distribution of GnRH, kisspeptin, and neurokinin B cell bodies and their projections in the human fetal hypothalamus.

Our data show that GNRH1, TAC3R and TAC3 genes were expressed by 60 days gestation in males and females. All five genes were detected in hypothalamic cDNA generated from second trimester specimens. Our preliminary data using immunocytochemistry mapped the expression of large populations of neurokinin B in the dorsomedial nucleus and the ventromedial nucleus of the human hypothalamus. In addition, the infundibular/arcuate nucleus was highly immunoreactive for neurokinin B with scattered neurons projecting to the median eminence. We found that the majority of infudibular/arcuate neurokinin B neurons co-express kisspeptin in both sexes by 15 weeks gestation, a feature observed in adult sheep and rodents.

These data demonstrate that many components of the neuroendocrine reproductive network important for activation of GnRH neurons are formed early in human brain development. This is the first investigation that surveys the expression and organization of kisspeptin and neurokinin B circuits in the developing human hypothalamus.