The Dynamics of Scavenger Receptor BI Expression During Luteinization.
Bibliographic record
Abstract
During luteinization, bulk cholesterol uptake to ovarian cells from blood high-density lipoproteins (HDL) is achieved by Scavenger Receptor BI (SR-BI). This is believed to be the major source of substrate for steroidogenesis. In the pig, we have shown weak expression of SR-BI in granulosa cells prior to ovulation, while robust in the corpus luteum (CL), where the protein localizes to the plasma membrane. Little is known about other species, indeed mice with SR-BI null mutation display estrous cycles and form CLs. We studied the expression of SR-BI during estrous cycle, the effects of uncoupling of ovulation and luteinization and the ovarian consequences of SR-BI knockout. Ovarian morphology was examined by light microscopy in HE-stained sections, SR-BI protein expression by immunofluorescence and progesterone determined by RIA. In Experiment 1, ovaries were collected from mature female WT mice at each stage of the estrous cycle (n=3 per stage). Expression of SR-BI was weak and diffuse in granulosa cells of developing follicles but became strong and localized to the cell membrane in CLs. In Experiment 2, follicular development was induced in immature female mice with PMSG and hCG. Animals received, 6 mg/kg of meloxicam (a cyclooxygenase inhibitor; MEL; n=3) or 10 mg of mifepristone (a progesterone receptor antagonist; RU; n=3) to block ovulation or vehicle only (n=3) and ovaries were collected 24 h after the hCG injection. Ovaries of animals treated with MEL or RU showed non-ovulated follicles, containing entrapped oocytes in unexpanded cumulus complexes. Membrane SR-BI expression was present throughout, but most intensely in the peripheral regions of the unruptured follicles. In Experiment 3, follicular development of mature WT and SR-BI-/- mice was stimulated by PMSG and hCG and animals were divided to receive vehicle or a combination of 20 mg/kg of mevinolin (an HMG-CoA reductase inhibitor; MEV) and 100 mg/kg of chloroquinone (an inhibitor of lysosomal processing of LDL; CHLORO) in a 2x2 factorial design (n=3 per group). At 18 h after hCG injection, approximately 6 h after expected ovulation, ovaries from SR-BI-/- mice presented small, luteal-like structures and large follicles with a thick, luteal-like layer of theca cells. Ovaries from MEV-CHLORO-treated, SR-BI-/- mice also displayed follicular cysts with blood filled cavities. Plasma progesterone concentrations were decreased in SR-BI-/- mice and further decreased by MEV-CHLORO treatment. It was concluded that (1) membrane expression of SR-BI increases in response to luteinization, (2) this event is not dependent on ovulation, (3) CL can be formed in the absence of SR-BI and (4) blocking cholesterol de novo synthesis and uptake from LDL and HDL sources leads to the formation of follicular cysts and reduces, but does not impair, ovarian steroidogenesis. Supported by CIHR grant FRN 11018 to BDM. MB is on leave from University of São Paulo and is supported by FAPESP (grant 06/52960-4).
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".