Bibliographic record
Abstract
In galliformes, prolactin (PRL) is thought to have both pro- and anti-gonadal effects on steroidogenesis by ovarian follicles dependent on its concentration. However, the role of the major isoform (glycosylated PRL, G-PRL) is unknown. Therefore, a comparison between non-glycosylated (NG-) and G-PRL on steroidogenesis in chicken different size class follicles was carried out. Contrary to the observations in mammals where G-PRL generally shows lower bioactivity than NG-PRL, both isoforms affected both basal and gonadotrophin-stimulated steroidogenesis over a broad concentration range. In granulosa cells of either preovulatory F3-F1 or prehierarchical 6-8 mm follicles, lower levels of NG-PRL stimulated basal estradiol (E2) and progesterone (P4) secretion but at higher levels this effect was reduced. However, G-PRL inhibited basal E2 and P4 secretion in a dose-dependent manner in prehierarchical granulosa cells in contrast to an inducible effect in preovulatory granulosa cells. In accordance with the data for steroids, levels of StAR, CYP11A1, CYP19A1 and 3β-HSD transcripts were up- or down-regulated by both isoforms. Furthermore, G-PRL was less potent than NG-PRL in suppressing FSH- or LH-induced E2 and P4 secretion in preovulatory granulosa cells, whereas G-PRL reduced but NG-PRL enhanced FSH-induced P4 secretion in prehierarchical granulosa cells. In the population of prehierarchical < 6 mm follicles, NG-PRL had a greater effect on suppressing FSH-induced E2 secretion than G-PRL, whereas G-PRL was more effective than NG-PRL in suppressing FSH-induced P4 production. In contrast, with the exception of the synergistic actions of LH and G-PRL on P4 production in the 4-6 mm follicles, both isoforms reduced LH-stimulated E2 and P4 production in all < 6 mm follicles. Thus, glycosylation of PRL can differentially modify its actions on basal and gonadotropin-stimulated steroidogenesis depending on the concentration, the type of gonadotropin (FSH or LH) and the stage of follicle development. Consistent with the effects of PRL on steroidogenesis, the PRL receptor (PRLR) was widely distributed in the follicular hierarchy, with the highest expression in the < 2 mm follicles and a progressive decline as the follicles matured. FSH had the greatest stimulatory effect on expression of PRLR in prehierarchical granulosa cells but this effect declined with follicle maturation, whereas LH showed no effects in all follicular classes examined. NG- and G-PRL were observed to have differential effects on basal and FSH-mediated PRLR expression according to the concentration and the stage of follicle development. As a newly identified ligand for the PRLR in non-mammalian vertebrates including chickens, PRL-like protein (PRL-L) had a similar expression pattern to PRLR during follicle development, with maximal expression in the < 2 mm follicles. Furthermore, PRL-L was more abundant in prehierarchical than preovulatory granulosa cells. FSH increased while LH did not affect expression of PRL-L in prehierarchical granulosa cells. Basal and FSH-induced PRL-L expression were differentially regulated by either isoform of PRL depending on the concentration. Therefore, it is suggested that the differential actions of PRL isoforms on follicular cell steroidogenesis are mediated through modulating the expression of PRLR and PRL-L. By using activators and/or inhibitors, we further demonstrated that in prehierarchical granulosa cells, multiple signaling pathways including PKA, PKC, PI3K-Akt-mTOR and AMPK were not only directly involved in but they could also converge to modulate ERK2 activity to regulate FSH-induced PRLR and PRL-L expression.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".