{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:34:27Z","timestamp":1758634467874},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":7827,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1983,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cortisol and insulin stimulated exponential growth of normal human mammary epithelium in short\u2010term monolayer culture. The response of cells depended on their organization into \u201cgrowth units\u201d on the surface of the culture dish; single cells did not respond. Growth of cells in the units ceased after only 3\u20134 doublings, ending in terminal differentiation. The 3\u20134 divisions that occurred in response to insulin and cortisol and that resulted in terminal differentiation, were not inhibited by short\u2010range signals normally transmitted at population confluence. When growing above confluence density in response to hormones, cells reduced volume to accommodate the \u201cterminal differentiation\u201d divisions while still largely preserving a monolayer. The longevity of populations of normal cells (9\u201314 divisions), which occurred in 3 or 4 passages, exceeded the average longevity of individual cells in one passage (3\u20134 divisions). This disparity between real and apparent longevity was due to the inhibition of growth of divisional cells within growth units, which occurred in concert with terminal differentiation of other cells in these units. Inhibited cells could be recruited to undergo terminal differentiation divisions in response to cortisol and insulin, but only when the growth units were disrupted and terminally differentiated cells were eliminated, which occurred at subculture. We refer to the inhibition of growth that occurs in growth units as \u201crenewal inhibition\u201d to distinguish it from population\u2010wide \u201cconfluence inhibition\u201d and to emphasize three other aspects: (1) it occurred in terminally differentiating growth units; (2) it occurred in the continued presence of an inductive hormonal stimulus for differentiative growth; and (3) it conserved less differentiated cells for recruitment to terminal differentiation. There are parallels between renewal inhibition in vitro and the signals that restrain growth of mammary cells in \u201cgrowth buds\u201d in vivo to preserve their capacity for multiple cycles of secretory differentiation. Differences in the behavior of normal and malignant breast cells in vitro suggest that renewal inhibition, rather than confluence inhibition, may be an important locus of growth control alteration in malignant transformation.<\/jats:p>","DOI":"10.1002\/jcp.1041160317","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T14:31:18Z","timestamp":1109428278000},"page":"385-396","source":"Crossref","is-referenced-by-count":14,"title":["Renewal inhibition of human mammary cell growth in vitro: Cortisol and the recruitment of cells to terminal differentiation"],"prefix":"10.1002","volume":"116","author":[{"given":"Charles M.","family":"McGrath","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert D.","family":"Soule","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"39","volume-title":"Growth Regulating Substances for Animal Cells in Culture","author":"Burk R. 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