Brain angiotensin and the female reproductive cycle.
The results consistently show from experiment to experiment that there is a surge of brain Ang II prior to the well known preovulatory LH surge. It should be pointed out that these experiments have been carried out by two different laboratories and with the help of different experimenters and some of the experiments have been repeated. Therefore, the consistency of the results is reassuring. It does appear that Ang II increases in the brain, specifically in the hypothalamus, probably in cells of the paraventricular nucleus about 1 hour before the LH levels in plasma rise to a peak. Since LH release from the anterior pituitary gland is stimulated by the release of LHRH from the arcuate nucleus into the median eminence, the results would suggest that Ang II stimulates the release of LHRH. The peak in the OVX of Ang II treated rats is sharp and short-lasting with a second, later peak. The LH surge follows the first peak and a second rise in LH follows the second Ang II peak. These data suggest that brain Ang II synthesized and stored in the brain plays a critical role in the female reproductive cycle by initiating the LH surge. The regulation of Ang II may be by estrogen and progesterone, but as the increase in angiotensinogen mRNA was not marked, the surge of Ang II appears to result more from the sudden release of stored Ang II than its synthesis. Thus, the question is what releases Ang II. Earlier studies showed that catecholamines release Ang II from neurons and not from glia involving alpha 2 receptor blockade to increase norepinephrine by inhibiting reuptake (7). An interaction between catecholamines, Ang II and LH had also been suggested earlier (18, 19). Therefore, a series of events triggered by steroids in proestrus may begin with increases in norepinephrine activating neuronal alpha 2 receptors and precipitating release of brain Ang II. This is represented diagrammatically in Figure 15. The Ang II surge stimulates the cells containing GnRH (gonadotropin releasing hormone) in the arcuate nucleus. The effect of Ang II on multiple GnRH cells amplifies the effect and GnRH is released into the portal vessels of the pituitary to stimulate the large LH release, from gonadotrope cells in the anterior pituitary, into the plasma that produces the LH surge. The effect of the LH surge is ovulation which ends the estrogen build up.(ABSTRACT TRUNCATED AT 400 WORDS)