PMID- 3034921 OWN - NLM STAT- MEDLINE DCOM- 19870710 LR - 20131121 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 131 IP - 2 DP - 1987 May TI - Functional differentiation of virgin mouse mammary epithelium in explant culture is dependent upon extracellular proline. PG - 190-9 AB - Depletion of proline from insulin, hydrocortisone, and prolactin-containing medium prior to incubating virgin mouse mammary explants prevents both DNA synthesis and functional differentiation in the mammary epithelial cells; however, DNA synthesis in the mammary stroma and total incorporation of radioactive amino acids into total protein appears to continue without hindrance. Removal of glycine instead of proline had no deleterious effect on either DNA replication in the hormone-stimulated epithelium or in its functional differentiation. Functional differentiation was determined by the induction of casein and alpha-lactalbumin synthesis in the insulin, hydrocortisone, and prolactin (IFPrl)-treated explant cultures. As a control, the induction of mouse mammary tumor virus (MMTV) gene expression, a corticosteroid-regulated function, was also measured. Neither the absence of proline or glycine prevented the glucocorticoid stimulation of MMTV gene expression. In contrast to mammary tissue from virgin mice, explants from nonpregnant primiparous mice responded fully to IFPrl stimulation with respect to DNA, casein, and alpha-lactalbumin synthesis in medium depleted of proline. These data suggest that the uncommitted epithelium of virgin mouse mammary glands requires the presence of exogenous proline in order to respond to lactogenic hormonal signals. We have demonstrated earlier that DNA synthesis is a prerequisite of functional differentiation in virgin mouse mammary explants (Smith and Vonderhaar, 1981, Dev. Biol., 88:167-179; Vonderhaar and Smith, 1982, J. Cell Sci, 53:97-114), although cytological differentiation proceeded unencumbered in explants prevented from synthesizing DNA. Here, without proline, neither cytological nor functional differentiation can be induced; this suggests that proline provides an essential metabolic interlock in the acquisition of lactogenic hormone responsiveness in uncommitted mouse mammary tissue. FAU - Smith, G H AU - Smith GH LA - eng PT - Journal Article PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Milk Proteins) RN - 9DLQ4CIU6V (Proline) RN - AE28F7PNPL (Methionine) SB - IM MH - Animals MH - Cell Differentiation/drug effects MH - DNA Replication MH - Female MH - Gene Expression Regulation MH - Mammary Glands, Animal/*ultrastructure MH - Mammary Tumor Virus, Mouse/genetics MH - Methionine/metabolism MH - Mice MH - Mice, Inbred C3H MH - Microscopy, Electron MH - Milk Proteins/biosynthesis MH - Organ Culture Techniques MH - Proline/*pharmacology EDAT- 1987/05/01 00:00 MHDA- 1987/05/01 00:01 CRDT- 1987/05/01 00:00 PHST- 1987/05/01 00:00 [pubmed] PHST- 1987/05/01 00:01 [medline] PHST- 1987/05/01 00:00 [entrez] AID - 10.1002/jcp.1041310208 [doi] PST - ppublish SO - J Cell Physiol. 1987 May;131(2):190-9. doi: 10.1002/jcp.1041310208.