Sulfated Neurosteroids: A new hypothalamic regulatory mechanism on reproductive function in female rats

CABRERA R.

Mendoza

Workshop; 2015 INTERNATIONAL WORKSHOP IN NEUROENDOCRINOLOGY.; 2015

IWNE

The neurosteroids are compounds synthesized de novo by neurons and glial cells in the central nervous system (CNS). They are involved in the neuroendocrine regulation of many physiological processes such as puberty, growth and reproduction. Among the most important cellular functions allosteric modulation of ionotropic stands regulating most transmissions and synaptic release of neurotransmitters such as GABA, glutamate, noradrenaline, dopamine and serotonin, both pre and postsynaptic level (Mellon and Griffin, 2002) Within the family of neurosteroids we find sulfated compounds. Dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate (SP) are the most abundant sulfated neurosteroids in the brain.They are involved in a large number of biological functions both in humans and in other mammals.Clearly we can see how PS, through different modulation of neurotransmitter receptors upregulates secretion of LH, without changing the pitch of the main neurotransmitters such as GABA and glutamate. This LH surge in turn is inhibited by COUMATE(an irreversible inhibitor of the STS enzyme), showing that imbalances in neurosulfatation and indirectly affect reproductive function.Furthermore, we observed that this hypothalamic sulfation affected against sex steroid hormonal variations, both at the enzymatic activity of EST at the molecular level as in STS gene expression. This indicates the interrelationship between sexual and reproductive development cycle by controlling gene expression of enzymes involved and fine tuning that is exerted on the brain on the enzyme activity of these enzymes. This would give this metabolic process functional relevance that has not been previously considered.Finally, we observed through the test of lordosis / mounted, how the changes to previously described hypothalamic level correlated with alterations at the behavioral level, demonstrating that lowering LH correlates with a decrease in% of lordosis supports a receptivity diminished or annulled .We conclude that neurosteroids sulfation in hypothalamus plays a key role affecting the reproductive function of the female rat, modulating GABAergic and glutamatergic receptors, wich induce regulation the release of LH and copulatory behavior.