Developing brain as a source of circulating norepinephrine in rats during the critical period of morphogenesis.

The development of individual organs and the whole organism is under the control by morphogenetic factors over the critical period of morphogenesis. This study was aimed to test our hypothesis that the developing brain operates as an endocrine organ during morphogenesis, in rats during the perinatal period (Ugrumov in Neuro Chem 35:837-850, 2010). Norepinephrine, which is a morphogenetic factor, was used as a marker of the endocrine activity of the developing brain, although it is also secreted by peripheral organs. In this study, it was first shown that the concentration of norepinephrine in the peripheral blood of neonatal rats is sufficient to ensure the morphogenetic effect on the peripheral organs and the brain itself. Using pharmacological suppression of norepinephrine production in the brain, but not in peripheral organs, it was shown that norepinephrine is delivered from the brain to the general circulation in neonatal rats, that is, during morphogenesis. In fact, even partial suppression of norepinephrine production in the brain of neonatal rats led to a significant decrease of norepinephrine concentration in plasma, suggesting that at this time the brain is an important source of circulating norepinephrine. Conversely, the suppression of the production of norepinephrine in the brain of prepubertal rats did not cause a change in its concentration in plasma, showing no secretion of brain-derived norepinephrine to the bloodstream after morphogenesis. The above data support our hypothesis that morphogenetic factors, including norepinephrine, are delivered from the developing brain to the bloodstream, which occurs only during the critical period of morphogenesis.

Brain is an important source of GnRH in general circulation in the rat during prenatal and early postnatal ontogenesis.

This study was aimed to test our hypothesis that, in contrast to adult rats, in fetuses and neonates, a large amount of the brain-derived GnRH is delivered to the general circulation. The GnRH concentration and content were estimated in general circulation and in the forebrain in rats on the 18th embryonic day (E18), E21, 3rd postnatal day (P3) and P30-36. Moreover, the GnRH concentration was measured in general circulation on E21 following microsurgical lesion on E18 of the forebrain containing most GnRH neurons. The concentration and content of GnRH in plasma on E18, E21 and P3 enormously exceeded those on P30-36. Reverse was true for the ontogenetic dynamics of the GnRH concentration in the forebrain. The lesion of the forebrain resulted in a drop of the GnRH concentration in plasma. The above data strongly suggest that the forebrain is the principal source of GnRH in general circulation in fetal and neonatal rats. Thus, the brain-derived GnRH is delivered to the general circulation in fetal and neonatal rats in amounts likely sufficient to influence the potential peripheral targets.