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Published on: October 4, 2019
Neuroprogesterone: key to estrogen positive feedback?
Paul Micevych1, Kiran K Soma, Kevin Sinchak
1Department of Neurobiology, David Geffen School of Medicine, Laboratory of Neuroendocrinology, Brain Research Institute at UCLA, Los Angeles, CA 90095-1763, USA. pmicevych@MEDNET.ucla.edu
Brain Research Reviews
|September 14, 2007
Summary
Estradiol stimulates progesterone synthesis in the brain, which is crucial for reproductive behaviors and the luteinizing hormone (LH) surge in female rats. This neurosteroidogenesis pathway involves membrane estrogen receptors and specific signaling cascades.
Area of Science:
- Neuroendocrinology
- Steroidogenesis
- Reproductive Biology
Background:
- Estradiol and progesterone regulate reproductive cycles and luteinizing hormone (LH) surges in female rats.
- Estrogen receptors (ER) and progesterone receptors coordinate reproductive physiology and behavior.
- Previous studies suggested an endogenous progesterone source in ovariectomized and adrenalectomized (ovx/adx) rats, essential for LH surges.
Purpose of the Study:
- To investigate the role of hypothalamic neuroprogesterone in estrogen-positive feedback and reproductive behavior.
- To elucidate the signaling pathways through which estradiol stimulates progesterone synthesis in the central nervous system (CNS).
Main Methods:
- Administration of estradiol and aminoglutethimide (AGT) in ovx/adx rats.
- Measurement of hypothalamic progesterone levels and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) expression.
- In vitro studies using astrocyte cultures to assess estradiol-induced progesterone synthesis via membrane ER, mGluR1a, and PLC-IP(3) pathway.
- Inhibition of progesterone synthesis or receptor blockade in estrogen-primed rats.
Main Results:
- Estradiol administration in ovx/adx rats induced an LH surge, and hypothalamic progesterone increased prior to this surge.
- Estradiol increased 3beta-HSD expression in the hypothalamus, indicating enhanced progesterone synthesis.
- Estradiol stimulated progesterone synthesis in astrocytes via membrane ERs, mGluR1a, and the PLC-IP(3) pathway, increasing intracellular calcium.
- Blocking progesterone synthesis or its receptor prevented proceptive behavior in estrogen-primed rats.
Conclusions:
- Hypothalamic neuroprogesterone, induced by estradiol, is necessary for estrogen-positive feedback and the LH surge.
- Estradiol stimulates neurosteroidogenesis in astrocytes through a specific membrane receptor-mediated signaling pathway.
- Neuroprogesterone plays a role in facilitating proceptive reproductive behaviors in female rats.
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