Plasma Growth Hormone Pulse Activation of Hepatic JAK-STAT5 Signaling: Developmental Regulation and Role in Male-Specific Liver Gene Expression
Bibliographic record
Abstract
The intracellular signaling molecule STAT5 is activated in rat liver by the intermittent male plasma GH pattern to a 10-fold higher level than by the more continuous pattern of plasma GH stimulation seen in females. Individual adult male rats are presently shown to exhibit large differences in liver STAT5 DNA-binding activity, which correlates with the presence of significant levels of GH in plasma at the time of liver excision. Examination of STAT5 activity as a function of postnatal development revealed that these intermittent pulses of liver STAT5 activity are first observed at 5 weeks of age, when plasma GH pulsation first begins and expression of male-specific, GH pulse-activated liver genes, including CYP2C11, first occurs. Prepubertal rats exhibited low liver STAT5 activity, likely a consequence of the absence of high plasma GH pulses in these animals. Proteins required for GH activation of STAT5 are expressed in liver before puberty, and correspondingly, STAT5 can be precociously activated by exogenous administration of GH pulses given to 2-week-old rats, albeit with a lower sensitivity to GH than is seen in hypophysectomized adult rats. However, this precocious activation of STAT5, via twice daily administration of GH for 7 days, did not lead to CYP2C11 expression or masculinization of hepatic enzyme profiles, unlike in GH pulse-stimulated hypophysectomized adult rats. Based on these findings we conclude: 1) liver STAT5 is repeatedly activated in adult male rats in direct response to the intermittent pattern of plasma GH stimulation; 2) the developmental onset of this STAT5 activation pattern supports the proposed requirement of STAT5 transcriptional activity for male-specific, GH pulse-regulated hepatic gene expression; and 3) the activation of STAT5 is, by itself, not sufficient to impart the adult male pattern of liver gene expression, suggesting a requirement for additional liver factors that are absent in prepubertal rats.
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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 | 0.000 | 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) | 0.001 | 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 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".