PreproTRH178–199 and Two Novel Peptides (pFQ7 and pSE14) Derived from Its Processing, Which Are Produced in the Paraventricular Nucleus of the Rat Hypothalamus, Are Regulated during Suckling**This work was supported by the National Science Foundation (Grant No. IBN-9507952 to E.A.N.).
Bibliographic record
Abstract
Suckling increases preproTRH messenger RNA in hypothalamic paraventricular neurons (PVN) and also markedly increases TRH release during the first period of lactation. Whether lactation alters preproTRH processing resulting in the generation of novel proTRH-derived peptides that may be involved in the regulation of PRL secretion lactation is not known. Therefore, in the present study we determine whether some other peptides derived from proTRH potentially contribute to lactation-induced PRL secretion. We have recently demonstrated that two members of the family of prohormone convertases PC1 and PC2 play a significant role in proTRH processing. PC1 is the major contributor in proTRH processing, whereas PC2 may have a specific role in cleaving TRH from its extended forms. In this study, we used a recombinant vaccinia virus system to coexpress rat preproTRH complementary DNA with PC1, PC2, and the neuropeptide 7B2 in GH4C1 cells (somatomammothophs, rat). We found that two novel peptides, preproTRH(178-184) (pFQ(7)), and preproTRH(186-199) (pSE(14)), were formed after the cleavage of their precursor preproTRH(178-199) (pFE(22)) by only PC2. Their formation was confirmed by microsequence analysis. Anatomical analyses revealed that these peptides are also found in the rat PVN. In addition, we found that pFE(22), pSE(14) and pFQ(7) produced a dose-dependent release of PRL from primary cultures of pituitary cells compared with one of the well studied secretagogues of PRL, TRH. To establish whether these peptides might play a role in vivo in the regulation of PRL release, we took rat litters on postnatal day 4, separated the pups from their mothers for 6 h, and then reunited the pups and mothers for 45 min. At the end of this period, the mothers were killed, acidic extracts of microdissected PVN were prepared and subjected to SDS-PAGE, followed by slicing and analysis by pFE(22) RIA. Forty-five minutes of suckling induced a marked 6-fold increase in serum levels of PRL. In addition, PVN levels of pFE(22) and pSE(14) increased approximately 5-fold during the same period in the acutely suckling females. Lactating animals that were separated from their litters and never reunited with their pups had low levels of PRL, and pFE(22) and pSE(14). These data provide the first evidence for alterations in proTRH processing in the PVN during lactation and suggest that the products of this altered processing may play a physiological role in the regulation of PRL secretion.
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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".