{
  "id": 3028728,
  "title": "Nuclear exclusion of menin drives functional MEN1 deficiency in non-MEN1 prolactinomas: mouse models and human biopsies",
  "url": "https://urgent.news/2026/08/24/nuclear-exclusion-of-menin-drives-functional-men1-deficiency-in-non",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-24T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.19.745771v1?rss=1"
  },
  "original_language": "en",
  "account": "Prolactinomas, the most common type of pituitary tumors, are frequently diagnosed in patients with Multiple Endocrine Neoplasia type 1, a condition caused by mutations in the MEN1 gene that produce the menin protein. While it is well-known that the loss of menin is associated with prolactinomas in patients with MEN1-associated tumors, its role in sporadic cases remains a mystery.\n\nTo gain further insight into this issue, researchers conducted experiments using two different mouse models. In these models, prolactinomas developed in females only. Despite the presence of the MEN1 gene in these mice, the expression of the MEN1 protein within the cells remained unchanged. However, when prolactinomas formed, the menin protein was found to be restricted to the cell's cytoplasm instead of being present in the nucleus, as is typically the case.\n\nInterestingly, male mice with either the MEN1 mutation or normal genetic makeup did not exhibit changes in the location of menin within their cells. The absence of menin in the nucleus of prolactinomas in male mice was linked to reduced levels of two proteins, p27 and Pten, increased levels of another protein, Ccnd1, and enhanced activity of a signaling pathway known as pAKT. These changes were further confirmed by administering dopamine, a drug that maintains the nuclear presence of menin in lactotroph cells (cells producing prolactin), and blocking dopamine or estrogen, both of which cause menin to move out of the nucleus.\n\nTo validate these findings in humans, the researchers analyzed pituitary biopsies from both normal individuals and those with prolactinomas. In normal pituitaries, both men and women showed proper localization of menin within the nucleus of lactotroph cells. Similarly, in prolactinomas from both genders, menin was found in both the nucleus and the cytoplasm when treated with dopamine. However, in a prolactinoma from an untreated female patient, menin was partially found in the nucleus, suggesting that the loss of nuclear menin in sporadic prolactinomas can be reversed by restoring its normal function. Therefore, the researchers propose that restoring the nuclear localization of menin could be a potential therapeutic strategy for treating sporadic prolactinomas.",
  "summary": "Prolactinomas, the most common secretory pituitary tumour subtype, frequently occur in patients with Multiple Endocrine Neoplasia type 1, caused by germline MEN1 mutations encoding menin. While menin loss is well established in MEN1-associated prolactinomas, its role in sporadic tumours remains unclear. We investigated menin expression, subcellular localization, and downstream signalling in two…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}