THE NEUROSTEROID TETRAHYDROPROGESTERONE ATTENUATES THE ENDOCRINE RESPONSE TO STRESS AND EXERTS GLUCOCORTICOID-LIKE EFFECTS ON VASOPRESSIN GENE-TRANSCRIPTION IN THE RAT HYPOTHALAMUS
Vk. Patchev et al., THE NEUROSTEROID TETRAHYDROPROGESTERONE ATTENUATES THE ENDOCRINE RESPONSE TO STRESS AND EXERTS GLUCOCORTICOID-LIKE EFFECTS ON VASOPRESSIN GENE-TRANSCRIPTION IN THE RAT HYPOTHALAMUS, Neuropsychopharmacology, 15(6), 1996, pp. 533-540
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 o
f CRH release and gene transcription. Those observations indicated tha
t, besides its sedative and analgesic activity, THP may also affect th
e neuroendocrine response to stress in a made resembling that of corti
costeroids. To examine this possibility, we compared the ability of TH
P, its precursor progesterone (P-4), and the glucocorticoids dexametha
sone (DEX) and corticosterone (CORT) to influence the pituitary-adrena
l response to acute emotional stress and the adrenalectomy-induced inc
rease in the gene transcription gf the stress-related peptide arginine
vasopressin (AVP) and of corticosteroid receptors (MX and GR) in the
brain. Pretreatment of rats with a single dose of THP or P-4 (50 mu g/
kg) significantly attenuated the elevation of plasma adrenocorticotrop
in (ACTH) and serum corticosterone after emotional stress, both steroi
ds were, however, less potent than a similar dose of DEX. Administrati
on of 1 mg of THP, CORT, or P-4 to adrenalectomized (ADX) rats attenua
ted the increase in AVP mRNA levels in the ventromedial subdivision of
the hypothalamic paraventricular nucleus (PVN), as compared with vehi
cle-treated ADX rats. However, whereas CORT and P-4 influenced the ADX
-induced increase in the transcription of both types of corticosteroid
receptors in the hippocampus, these were unaffected by THP. In contra
st to the glucocorticoids, THP and P-4 failed to decrease plasma ACTH
levels in rats deprived of endogenous steroids. These results demonstr
ate that the neurosteroid THP and its precursor P-4 resemble glucocort
icoids in their suppression of the pituitary-adrenal response to emoti
onal stress; however, THP influences the transcription of glucocortico
id-responsive genes in brain structures involved in the regulation of
the hypothalamo-pituitary-adrenal system in a fashion that is quite di
stinct from that obtained with glucocorticoids. (C) 1996 American Coll
ege of Neuropsychopharmacology