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Saturday, October 10, 2009

Tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release of corticotropin-releasing hormone

The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus.

Patchev VK, Shoaib M, Holsboer F, Almeida OF.Department of Neuroendocrinology, Max Planck Institute for Psychiatry, Munich, Germany.

The ring-A-reduced progesterone derivative 5 alpha-pregnan-3 alpha-ol-20-one (tetrahydroprogesterone) is synthesized under normal physiological conditions in the brain and is a potent modulator of the GABA receptor.

This neurosteroid has significant sedative and anxiolytic properties.

Corticotropin-releasing hormone plays a major role in stress-induced activation of the hypothalamo-pituitary-adrenal axis, and sustained hyperactivity of hypothalamic corticotropin-releasing hormone-producing neurons may be causally related to both, increased pituitary-adrenal secretion and behavioural symptoms observed in anxiety and affective disorders. We investigated the effect of tetrahydroprogesterone on corticotropin-releasing hormone-induced anxiety, the basal and methoxamine-stimulated release of corticotropin-releasing hormone from hypothalamic organ explants in vitro, and adrenalectomy-induced up-regulation of the gene expression of corticotropin-releasing hormone in the hypothalamic paraventricular nucleus in rats. At doses of 5 and 10 micrograms i.c.v., tetrahydroprogesterone counteracted the anxiogenic action of 0.5 microgram of corticotropin-releasing hormone.

Tetrahydroprogesterone did not alter the basal release of corticotropin-releasing hormone in vitro, but suppressed the stimulatory effect of the alpha 1-adrenergic agonist methoxamine on this parameter. Measurements of the steady-state levels of mRNA coding for corticotropin-releasing hormone by quantitative in situ-hybridization histochemistry revealed that tetrahydroprogesterone was equipotent with corticosterone in preventing adrenalectomy-induced up-regulation of peptide gene expression.

Systemic administration of tetrahydroprogesterone also restrained adrenalectomy-induced thymus enlargement.

These results demonstrate that tetrahydroprogesterone has anxiolytic effects that are mediated through interactions with hypothalamic corticotropin-releasing hormone in both, genomic and non-genomic fashions.

http/www.ncbi.nlm.nih.gov/pubmed/7816204

Allopregnanolone (tetrahydroprogesterone)

From Wikipedia, the free encyclopedia

Allopregnanolone, also known as 3α,5α-tetrahydroprogesterone or THP, is an important neurosteroid in the human brain.

It is a metabolite of progesterone and a barbiturate-like modulator of central gamma-aminobutyric acid (GABA) receptors that modify a range of behaviors, including the stress response.

The 5β epimer of this compound is known as pregnanolone, and has very similar properties to allopregnanolone.

Both compounds are found endogenously and have similar hypnotic and anxiolytic effects.

http/en.wikipedia.org/wiki/Allopregnanolone

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