john herr psychologist los gatos saratoga california

On Sabbatical

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TITLE: The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus.
AUTHOR: Patchev VK; Hassan AH; Holsboer DF; Almeida OF
AUTHOR AFFILIATION: Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.
SOURCE: Neuropsychopharmacology 1996 Dec;15(6):533-40
NLM CIT. ID: 97101909
ABSTRACT: The neurosteroid tetrahydroprogesterone (5 alpha-pregnan-3 alpha-ol-20-one, allopregnanolone, THP), has been previously shown to counteract the anxiogenic effects of corticotropin-releasing hormone (CRH) and to interfere with noradrenergic and corticosteroid-mediated regulation of CRH release and gene transcription. Those observations indicated that, besides its sedative and analgesic activity, THP may also affect the neuroendocrine response to stress in a mode resembling that of corticosteroids. To examine this possibility, we compared the ability of THP, its precursor progesterone (P4), and the glucocorticoids dexamethasone (DEX) and corticosterone (CORT) to influence the pituitary-adrenal response to acute emotional stress and the adrenalectomy-induced increase in the gene transcription of the stress-related peptide arginine vasopressin (AVP) and of corticosteroid receptors (MR and GR) in the brain. Pretreatment of rats with a single dose of THP or P4 (50 micrograms/kg) significantly attenuated the elevation of plasma adrenocorticotropin (ACTH) and serum corticosterone after emotional stress; both steroids were, however, less potent than a similar dose of DEX. Administration of 1 mg of THP, CORT, or P4 to adrenalectomized (ADX) rats attenuated the increase in AVP mRNA levels in the ventromedial subdivision of the hypothalamic paraventricular nucleus (PVN), as compared with vehicle-treated ADX rats. However, whereas CORT and P4 influenced the ADX-induced increase in the transcription of both types of corticosteroid receptors in the hippocampus, these were unaffected by THP. In contrast to the glucocorticoids, THP and P4 failed to decrease plasma ACTH levels in rats deprived of endogenous steroids. These results demonstrate that the neurosteroid THP and its precursor P4 resemble glucocorticoids in their suppression of the pituitary-adrenal response to emotional stress; however, THP influences the transcription of glucocorticoid-responsive genes in brain structures involved in the regulation of the hypothalamo-pituitary-adrenal system in a fashion that is quite distinct from that obtained with glucocorticoids.
Neuroprotective Agents/*PHARMACOLOGY
Receptors, Steroid/*DRUG EFFECTS
Stress, Psychological/BLOOD/*METABOLISM
Transcription, Genetic/*DRUG EFFECTS
Anti-Inflammatory Agents, Steroidal/PHARMACOLOGY
Glucocorticoids, Synthetic/PHARMACOLOGY
Rats, Wistar
Support, Non-U.S. Gov't
REGISTRY NUMBERS: 0 (Anti-Anxiety Agents)
0 (Anti-Inflammatory Agents, Steroidal)
0 (Glucocorticoids, Synthetic)
0 (Neuroprotective Agents)
0 (Receptors, Steroid)
113-79-1 (Argipressin)
128-20-1 (Pregnanolone)
4406-35-3 (pregnan-3-ol-20-one)
50-02-2 (Dexamethasone)
50-22-6 (Corticosterone)
57-83-0 (Progesterone)
9002-60-2 (Corticotropin)

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On Sabbatical!

When my office lease expired at the end of 2004, I decided to turn it into a "sabbatical" from my private practice. Many years ago, in my grandfather's 89th year of life, he told me, "John, it is important to smell the roses while you can still smell them." His life gave living a very good reputation. It is also true that the pursuit of that philosophy required my grandfather to to re-open his assay office/ore market in Wickenburg, Arizona as a 75-year-old because he had run a little short of retirement money. Thus, if blessed with his luck and health, I'll be back.. --jjh

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