SAT-416 IGSF1 Does Not Regulate FSH Synthesis or Secretion
Bibliographic record
Abstract
Loss of function mutations in the human X-linked immunoglobulin superfamily, member 1 (IGSF1) gene result in central hypothyroidism, often associated with macroorchidism. Igsf1-deficient mice are also centrally hypothyroid due to impaired TRH action in the pituitary. The mechanisms underlying macroorchidism are unclear and disputed. IGSF1 was originally characterized as an inhibin B co-receptor. As inhibin B negatively regulates FSH secretion, it was hypothesized that loss of IGSF1 would impair inhibin B action, leading to elevated FSH levels and enhanced Sertoli cell proliferation during development. Yet, in direct contradiction to this model, IGSF1 does not bind inhibin A or B in heterologous binding assays. Our preliminary data further indicate that FSHβ subunit (Fshb) mRNA expression is similarly antagonized by inhibin A and B in pituitary cultures from wild-type and Igsf1-deficient mice. More recently, IGSF1 was proposed to inhibit activin type IB receptor (ALK4) signaling. As activins stimulate FSH, loss of this inhibition should lead to increased FSH. However, neither humans nor mice with IGSF1-deficiency have elevated FSH and IGSF1 expression in FSH-producing gonadotrope cells is negligible. Additionally, Igsf1-deficient mice have normal serum LH and inhibin B levels, as well as testicular weights, histology, and semen parameters. Previous methods used to demonstrate IGSF1 regulation of a human FSHB promoter-reporter were conducted in a heterologous system in which such reporters lack activin/ALK4-dependent activity. We demonstrate that overexpression of IGSF1 in homologous LβT2 gonadotrope-like cells does not impair induction of murine or human Fshb/FSHB promoter-reporters by activin A or a constitutively active form of ALK4. Collectively, the available data fail to support a role for IGSF1 in FSH regulation by activins, inhibins, or otherwise.
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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) | 0.005 | 0.002 |
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".