Abstract
A liquid chromatography-mass spectrometry method was developed to quantify a panel of 8 neurosteroids in the brain: corticosterone, pregnenolone, deoxycorticosterone (DOC), dihydrodeoxycorticosterone (DHDOC), progesterone, dihydroprogesterone (DHP), allopregnanolone and testosterone. The method showed good linearity, sensitivity and precision, and was used to determine steroid concentrations in plasma and 5 brain subregions (frontal cortex, hypothalamus, hippocampus, amygdala and brainstem) from male and female rats killed under basal conditions or 30 min after acute stress exposure (2 min forced swimming).
Corticosterone, DOC and progesterone concentrations were significantly greater in the plasma and brain of both sexes following stress; however the response in plasma was exaggerated in females compared to males. This sex difference was also observed in the majority of brain regions for DOC and progesterone, but not corticosterone. Despite observing no changes in plasma concentrations of pregnenolone and the 5-alpha reduced steroids, DHDOC and DHP after stress, concentrations were greater in the brain, and this effect was more pronounced in females compared to males. Basal plasma and brain concentrations of allopregnanolone were significantly higher in females, compared to males. Moreover, following stress a significant increase in allopregnanolone was observed only in the females. Testosterone was undetectable in females, and stress had no significant effect on circulating or brain concentrations in either sex.
Together these data indicate local regulation of neurosteroids in the brain following acute stress, especially for 5alpha- and 3alpha-hydroxysteroid dehydrogenase-reduced steroids. Furthermore, the greater neurosteroid response to stress in females, suggests sex-specific expression of steroidogenic enzymes in the brain.
Corticosterone, DOC and progesterone concentrations were significantly greater in the plasma and brain of both sexes following stress; however the response in plasma was exaggerated in females compared to males. This sex difference was also observed in the majority of brain regions for DOC and progesterone, but not corticosterone. Despite observing no changes in plasma concentrations of pregnenolone and the 5-alpha reduced steroids, DHDOC and DHP after stress, concentrations were greater in the brain, and this effect was more pronounced in females compared to males. Basal plasma and brain concentrations of allopregnanolone were significantly higher in females, compared to males. Moreover, following stress a significant increase in allopregnanolone was observed only in the females. Testosterone was undetectable in females, and stress had no significant effect on circulating or brain concentrations in either sex.
Together these data indicate local regulation of neurosteroids in the brain following acute stress, especially for 5alpha- and 3alpha-hydroxysteroid dehydrogenase-reduced steroids. Furthermore, the greater neurosteroid response to stress in females, suggests sex-specific expression of steroidogenic enzymes in the brain.
| Original language | English |
|---|---|
| Publication status | Unpublished - Jul 2018 |
| Event | International Congress of Neuroendocrinology - Westin Harbour Castle , Toronto, Canada Duration: 15 Jul 2018 → 18 Jul 2018 http://www.icn2018.org/ |
Conference
| Conference | International Congress of Neuroendocrinology |
|---|---|
| Abbreviated title | ICN2018 |
| Country/Territory | Canada |
| City | Toronto |
| Period | 15/07/18 → 18/07/18 |
| Internet address |