Abstract
The reduced metabolites of progesterone (3α-hydroxy-5α-pregnan-20-one or 3α,5α-P) and deoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one or 5α-THDOC) exhibit a γ-aminobutyric acid (GABA) agonist pharmacological profile and bind with high affinity to a unique steroid recognition site on the GABA(A) receptor complex (GRC). In female rats, peak levels of 3α,5α-P occur between proestrus and estrus and at concentrations which appear sufficient to affect GRC-mediated inhibitory events. Therefore, steroid modulation of the binding of [35S]t-butylbicyclophosphorothionate was conducted to examine sensitivity of the GRC during the estrus cycle. The results in unwashed tissue (cortex, cerebellum, hippocampus and striatum) indicated that 3α,5α-P was most potent in estrus. Subsequent studies in washed tissue and in washed tissue plus 3 μM (+)bicuculline indicated that 3α,5α-P was more potent in diestrus 1 than in estrus. Brain regional differences in potency of 3α,5α-P were also observed. Overall, the results in washed tissue suggest that an inherent change in the sensitivity of the GRC occurs during the estrus cycle, whereas the results in unwashed tissue may be influenced by the presence of endogenous GRC-active neurosteroids and GABA. The change in sensitivity of the GRC during the estrus cycle may occur to help maintain homeostatic regulation of brain excitability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1374-1379 |
| Number of pages | 6 |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 265 |
| Issue number | 3 |
| State | Published - 1993 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
The influence of estrus cycle on neurosteroid potency at the γ- aminobutyric acid(A) receptor complex. / Finn, Deborah (Deb); Gee, K. W.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 265, No. 3, 1993, p. 1374-1379.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The influence of estrus cycle on neurosteroid potency at the γ- aminobutyric acid(A) receptor complex
AU - Finn, Deborah (Deb)
AU - Gee, K. W.
PY - 1993
Y1 - 1993
N2 - The reduced metabolites of progesterone (3α-hydroxy-5α-pregnan-20-one or 3α,5α-P) and deoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one or 5α-THDOC) exhibit a γ-aminobutyric acid (GABA) agonist pharmacological profile and bind with high affinity to a unique steroid recognition site on the GABA(A) receptor complex (GRC). In female rats, peak levels of 3α,5α-P occur between proestrus and estrus and at concentrations which appear sufficient to affect GRC-mediated inhibitory events. Therefore, steroid modulation of the binding of [35S]t-butylbicyclophosphorothionate was conducted to examine sensitivity of the GRC during the estrus cycle. The results in unwashed tissue (cortex, cerebellum, hippocampus and striatum) indicated that 3α,5α-P was most potent in estrus. Subsequent studies in washed tissue and in washed tissue plus 3 μM (+)bicuculline indicated that 3α,5α-P was more potent in diestrus 1 than in estrus. Brain regional differences in potency of 3α,5α-P were also observed. Overall, the results in washed tissue suggest that an inherent change in the sensitivity of the GRC occurs during the estrus cycle, whereas the results in unwashed tissue may be influenced by the presence of endogenous GRC-active neurosteroids and GABA. The change in sensitivity of the GRC during the estrus cycle may occur to help maintain homeostatic regulation of brain excitability.
AB - The reduced metabolites of progesterone (3α-hydroxy-5α-pregnan-20-one or 3α,5α-P) and deoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one or 5α-THDOC) exhibit a γ-aminobutyric acid (GABA) agonist pharmacological profile and bind with high affinity to a unique steroid recognition site on the GABA(A) receptor complex (GRC). In female rats, peak levels of 3α,5α-P occur between proestrus and estrus and at concentrations which appear sufficient to affect GRC-mediated inhibitory events. Therefore, steroid modulation of the binding of [35S]t-butylbicyclophosphorothionate was conducted to examine sensitivity of the GRC during the estrus cycle. The results in unwashed tissue (cortex, cerebellum, hippocampus and striatum) indicated that 3α,5α-P was most potent in estrus. Subsequent studies in washed tissue and in washed tissue plus 3 μM (+)bicuculline indicated that 3α,5α-P was more potent in diestrus 1 than in estrus. Brain regional differences in potency of 3α,5α-P were also observed. Overall, the results in washed tissue suggest that an inherent change in the sensitivity of the GRC occurs during the estrus cycle, whereas the results in unwashed tissue may be influenced by the presence of endogenous GRC-active neurosteroids and GABA. The change in sensitivity of the GRC during the estrus cycle may occur to help maintain homeostatic regulation of brain excitability.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027426171&partnerID=8YFLogxK
M3 - Article
C2 - 8389864
AN - SCOPUS:0027426171
VL - 265
SP - 1374
EP - 1379
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 3
ER -