Testosterone and Corticosterone in the Mesocorticolimbic System of Male Rats: Effects of Gonadectomy and Caloric Restriction
Bibliographic record
Abstract
Steroid hormones can modulate motivated behaviors through the mesocorticolimbic system.Gonadectomy (GDX) is a common method to determine how steroids influence the mesocorticolimbic system, and caloric restriction (CR) is often used to invigorate motivated behaviors.A common assumption is that the effects of these manipulations on brain steroid levels reflects circulating steroid levels.We now know that the brain regulates local steroid levels in a region-specific manner; however, previous studies have low spatial resolution.Using ultrasensitive liquid chromatography tandem mass spectrometry, we examined steroids in microdissected regions of the mesocorticolimbic system (ventral tegmental area, nucleus accumbens, medial prefrontal cortex).We examined whether GDX or CR influences systemic and local steroids, particularly testosterone (T) and steroidogenic enzyme transcripts.Adult male rats underwent a GDX surgery and/or CR for either 2 or 6 weeks.Levels of T, the primary steroid of interest, were higher in all brain regions than in the blood, whereas corticosterone (CORT) was lower in the brain than in the blood.Importantly, GDX completely eliminated T in the blood and lowered T in the brain.Yet, T remained present in the brain, even 6 weeks after GDX.CR decreased both T and CORT in the blood and brain.Steroidogenic enzyme (Cyp17a1, 3b-hydroxysteroid dehydrogenase, aromatase) transcripts and androgen receptor transcripts were expressed in the mesocorticolimbic system and differentially affected by GDX and CR.Together, these results suggest that T is synthesized within the mesocorticolimbic system.These results provide a foundation for future studies examining how neurosteroids influence behaviors mediated by the mesocorticolimbic system.(Endocrinology 159: 450-464, 2018) S teroids influence behavior, neural activity, and neural cytoarchitecture via multiple pathways (1).Neuroactive steroids include sex steroids, such as testosterone (T) and 17b-estradiol (E 2 ), as well as glucocorticoids, such as corticosterone (CORT).These steroids have traditionally been considered to be produced in the gonads or adrenals.Steroids that are locally synthesized in the brain are referred to as neurosteroids, such as dehydroepiandrosterone (DHEA) and pregnenolone (2).Recent evidence suggests that T, E 2 , and CORT can also be produced in the brain (2-5).For example, Hojo et al. (4) found that T was synthesized in hippocampal slices when the precursors androstenedione or androstenediol were added.The enzymes necessary for neurosteroid synthesis are present in the mammalian nervous system (6-8) (Fig. 1).However, most studies have examined
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".