The Calcium Signaling Pathway Regulates Leydig Cell Steroidogenesis through a Transcriptional Cascade Involving the Nuclear Receptor NR4A1 and the Steroidogenic Acute Regulatory Protein
Bibliographic record
Abstract
In the gonads and adrenal glands, the transient increase in steroidogenesis after hormonal stimulation requires modulation of steroidogenic acute regulatory protein (Star) expression and activity in a tightly regulated process involving cAMP and Ca(2+). In Leydig cells, the cAMP and Ca(2+) pathways account for most if not all of LH-induced steroidogenesis. Although the cAMP-activated molecular network has been well characterized in Leydig cells, little is known about the molecular cascade triggered by the Ca(2+) signaling pathway and the transcription factors responsible for mediating the genomic response. It is established that LH induces an increase in cytoplasmic Ca(2+) from the endoplasmic reticulum primarily through the ryanodine receptors. Previous reports also suggested a role of the Ca(2+) signaling pathway in Star expression based on the fact that inhibition of the Ca(2+)/calmodulin (CaM) protein kinase pathway greatly impaired Star expression in Leydig and adrenal cells. In this study, we used ryanodine receptors and CaM antagonists to show that the increase in intracellular Ca(2+) level is an essential modulator of progesterone synthesis through the regulation of Star gene expression in MA-10 Leydig cells. Furthermore, we mapped a Ca(2+)/CaM-sensitive element in the Star promoter, which led to the identification of the nuclear receptor 4A1 (NR4A1) as a key mediator of the Ca(2+)/CaM signaling pathway in these cells. These data provide new insights into the Ca(2+) molecular pathway essential for steroidogenesis in Leydig cells.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".