The Orphan Nuclear Receptor NR4A1 Is a Negative Regulator of DHT-Induced Rat Preantral Follicular Growth.
Bibliographic record
Abstract
NR4A1, an orphan nuclear receptor, is involved in the transcriptional regulation of ovarian steroidogenesis and is down-regulated by excess androgen in human ovary. Insulin-like 3 (Insl3), a theca cell derived growth factor, G1/S-specific cyclin-D2 (Ccnd2) and follicle stimulating hormone receptor (FSHR) expression are important for follicle development. Although androgens are known to play important regulatory roles in ovarian follicle growth, whether and how they interact with NR4A1 in the control of preantral follicular growth is poorly understood. The objective of present study was to examine the role and regulation of NR4A1 in the control of rat preantral follicular growth by 5a-dihydrotestosterone (DHT). We hypothesize that DHT induces preantral follicle growth and represses NR4A1 expression and that down-regulated NR4A1 reduces DHT-induced preantral follicle growth. Moreover, NR4A1 promotes preantral follicles growth by up-regulating androgen production and Insl3 expression. Using a chronically androgenized rat model (implant daily release dose=83 μg DHT from day 21-105), rat preantral follicle (diameter: 150–180 μm) cultures and virus-mediated gene delivery, we examined the actions and interactions of DHT and NR4A1 in the regulation of preantral follicle growth. Immunofluouresence microscopy of ovarian sections from DHT-treated rats demonstrated increased Ki67 staining in preantral follicles. Preantral follicles from DHT-treated rats cultured for 4 days also exhibited increased growth and up-regulation of mRNA abundance for Ccnd2 and FSHR. Similarly, DHT (1μM) increased preantral follicular growth and Ccnd2 and FSHR mRNA abundance in vitro. NR4A1 expression was high in theca cells and was down-regulated by DHT in vivo and in vitro. Forced expression of NR4A1 augmented preantral follicular growth, androstenedione production and Insl3 expression in vitro. Inhibiting the action of androgen (by anti-androgen flutamide) or Insl3 (by Insl3 receptor antagonist, Insl3 B-chain) reduced NR4A1-induced preantral follicular growth. Furthermore, NR4A1 over-expression enhanced DHT-induced preantral follicular growth, a response attenuated by inhibiting Insl3. In conclusion, DHT induces preantral follicular growth and attenuates NR4A1 expression in vivo and in vitro. NR4A1 promotes preantral follicle growth by up-regulating follicular androgen biosynthesis and Insl3 expression. NR4A1 is a negative regulator in DHT-induced rat preantral follicular growth. [Supported by a grant from CIHR (BKT); KX is a recipient of a CIHR-REDIH graduate scholarship].
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".