Schaefer F V
Differentiation. 1986;32(3):238-44. doi: 10.1111/j.1432-0436.1986.tb00579.x.
Normal mammary gland development during pregnancy follows a coordinated program of morphological development (formation of lobuloalveoli) and biochemical differentiation (casein production). In culture, whole mammary glands of Balb/c mice can be similarly induced by application of a mixture of insulin, prolactin, aldosterone and hydrocortisone (IPAH) for 7 days. Our previous reports have shown that lobuloalveolar development, induced by IPAH, is competitively inhibited by the simultaneous presence of dibutyryl cyclic AMP (Bt2cAMP), prostaglandins (PGs) E1, E2, and B1, and papaverine (pap). However, if this mixture is not added until day 4, lobuloalveolar development is relatively unaffected but casein synthesis is repressed. This report explores the mechanism by which cyclic adenine nucleotides and prostaglandins interfere with the normal developmental pathway. The accumulation of alpha- and beta-casein mRNAs induced by prolactin, hydrocortisone and aldosterone is blocked by the combination of Bt2cAMP, PGs E1, E2, and B1, and pap added to the medium for the final 3 days (days 4-7). Under these conditions the glands retain their lobuloalveoli, and little squamous metaplasia can be discerned. Furthermore, de novo synthesis of both caseins is selectively inhibited, despite the continued presence of casein mRNAs in the glands and normal protein synthesis. In contrast, the synthesis of keratin is stimulated. Incomplete mixtures of Bt2cAMP and pap or the combination of PGs E1, E2, and B1, are only partly effective in preventing the accumulation of casein mRNAs. All three mixtures bring about similar effects on both alpha- and beta-casein mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
孕期正常的乳腺发育遵循形态发育（小叶腺泡形成）和生化分化（酪蛋白产生）的协调程序。在培养中，给Balb/c小鼠的完整乳腺施加胰岛素、催乳素、醛固酮和氢化可的松的混合物（IPAH）7天，可产生类似的诱导效果。我们之前的报告显示，IPAH诱导的小叶腺泡发育会受到二丁酰环磷腺苷（Bt2cAMP）、前列腺素（PGs）E1、E2和B1以及罂粟碱（pap）同时存在的竞争性抑制。然而，如果直到第4天才添加这种混合物，小叶腺泡发育相对不受影响，但酪蛋白合成会受到抑制。本报告探讨了环腺嘌呤核苷酸和前列腺素干扰正常发育途径的机制。在最后3天（第4 - 7天）向培养基中添加Bt2cAMP、PGs E1、E2和B1以及pap的组合，可阻断催乳素、氢化可的松和醛固酮诱导的α-和β-酪蛋白mRNA的积累。在这些条件下，腺体保留其小叶腺泡，几乎看不到鳞状化生。此外，尽管腺体中持续存在酪蛋白mRNA且蛋白质合成正常，但两种酪蛋白的从头合成均受到选择性抑制。相反，角蛋白的合成受到刺激。Bt2cAMP和pap的不完全混合物或PGs E1、E2和B1的组合在阻止酪蛋白mRNA积累方面仅部分有效。所有三种混合物对α-和β-酪蛋白mRNA都产生类似的影响。（摘要截断于250字）
