Estradiol regulation of progesterone synthesis in the brain

Abstract

Steroidogenesis is now recognized as a global phenomenon in the brain, but how it is regulated and its relationship to circulating steroids of peripheral origin have remained more elusive issues. Neurosteroids, steroids synthesized de novo in nervous tissue, have a large range of actions in the brain, but it is only recently that the role of neuroprogesterone in the regulation of arguably the quintessential steroid dependent neural activity, regulation of the reproduction has been appreciated. Circuits involved in controlling the LH surge and sexual behaviors were thought to be influenced by estradiol and progesterone synthesized in the ovary and perhaps the adrenal. It is now apparent that estradiol of ovarian origin regulates the synthesis of neuroprogesterone, and it is the locally produced neuroprogesterone that is involved in the initiation of the LH surge and subsequent ovulation. In this model, estradiol induces the transcription of progesterone receptors while stimulating synthesis of neuroprogesterone. Although the complete signaling cascade has not been elucidated, many of the features have been characterized. The synthesis of neuroprogesterone occurs primarily in astrocytes and requires the interaction of membrane associated estrogen receptor-α with metabotropic glutamate receptor-1a. This G protein-coupled receptor activates a phospholipase C that in turn increases inositol trisphosphate (IP 3 ) levels mediating the release of intracellular stores of Ca 2+ via an IP 3 receptor gated Ca +2 channel. The large increase in free cytoplasmic Ca 2+ ([Ca 2+ ] i ) stimulates the synthesis of progesterone, which can then diffuse out of the astrocyte and activate estradiol-induced progesterone receptors in local neurons to trigger the neural cascade to produce the LH surge. Thus, it is a cooperative action of astrocytes and neurons that is needed for estrogen positive feedback and stimulation of the LH surge.

Sex differences in the physiology of eating

“…Recognition of its importance has fundamentally changed endocrinology in recent decades. In the brain, locally produced steroids are called neurosteroids (240,477,478,611). In anthropoid primates, the adrenal glands are a major source of precursor molecules for local steroid synthesis.…”

Estrogen Receptors and Type 1 Metabotropic Glutamate Receptors Are Interdependent in Protecting Cortical Neurons against β-Amyloid Toxicity

“…Finally, we examined whether ER␣ and mGlu1 receptors could also interact in stimulating polyphosphoinositide hydrolysis, which is the canonical signal transduction pathway activated by mGlu1 receptors (Ferraguti et al, 2008). Stimulation of PI hydrolysis produced by membrane ER␣ and mGlu1 receptors is required for the synthesis of neuroprogesterone in hypothalamic astrocytes (Micevych and Sinchak, 2008a;Kuo et al, 2009 …”

The Effects of Dietary Soybean Fermented with Aspergillus oryzae or Bacillus natto on Egg Production and Egg Lipid Composition in Layer

“…Even though the present study did not analyze the concentration of isoflavones in the blood, it might be possible that the positive increase in egg production of layers fed with fermented soybeans was due to the estrogenic effect of isoflavones. It is thought that an increase in the concentration of estrogen in circulating blood can trigger secretion of luteinizing hormone (LH) and, consequently, ovulation (Micevych and Sinchak, 2008).…”