Endocrine regulation of estrogen synthesis in the hippocampus?

Estradiol synthesis in the ovaries is regulated via feedback mechanisms mediated by gonadotrophin-releasing hormone (GnRH) and gonadotrophins, secreted by the hypothalamus and the pituitary, respectively. Estradiol synthesis also takes place in the hippocampus. In hippocampal slice cultures of female animals, GnRH regulates estradiol synthesis dose-dependently. Hence, both hippocampal and ovarian estradiol synthesis are synchronized by GnRH. Hippocampus-derived estradiol is essential to synapse stability and maintenance because it stabilizes the spine cytoskeleton of hippocampal neurons. Inhibition of hippocampal estradiol synthesis in mice, however, results in loss of spines and spine synapses in females, but not in males. Stereotaxic application of GnRH to the hippocampus of female rats confirms the regulatory role of GnRH on estradiol synthesis and synapse density in the female hippocampus in vivo. This regulatory role of GnRH necessarily results in estrus cyclicity of spine density in the hippocampus of females.