EVIDENCE THAT GROWTH-HORMONE STIMULATES MILK SYNTHESIS BY DIRECT ACTION ON THE MAMMARY-GLAND AND THAT PROLACTIN EXERTS EFFECTS ON MILK SECRETION BY MAINTENANCE OF MAMMARY DEOXYRIBONUCLEIC-ACID CONTENT AND TIGHT JUNCTION STATUS
EVIDENCE THAT GROWTH-HORMONE STIMULATES MILK SYNTHESIS BY DIRECT ACTION ON THE MAMMARY-GLAND AND THAT PROLACTIN EXERTS EFFECTS ON MILK SECRETION BY MAINTENANCE OF MAMMARY DEOXYRIBONUCLEIC-ACID CONTENT AND TIGHT JUNCTION STATUS
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DOI：
10.1210/en.135.3.1119
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发表时间：
1994-09-01
期刊：
影响因子：
4.8
通讯作者：
GARDNER, M
中科院分区：
文献类型：
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作者：
FLINT, DJ;GARDNER, M
PRL和GH都在维持大鼠泌乳中发挥作用，尽管GH只能将幼仔体重增加维持在对照值的50%左右，而PRL在没有GH的情况下可以维持体重增加接近90%。在这项研究中，我们研究了泌乳素和生长激素缺乏症（使用溴隐亭和抗血清大鼠生长激素）对泌乳大鼠的产奶量和成分的影响。用溴隐亭治疗以抑制PRL分泌48小时导致产奶量下降57%，同时乳蛋白和乳糖产量下降，但脂肪产量没有下降。这导致生产的牛奶具有较低的乳糖浓度，但增加的蛋白质，特别是脂肪的浓度（增加100%），这表明GH通过保持能量丰富的牛奶为新生儿当PRL分泌减少的辅助作用。这种乳汁合成的减少伴随着乳腺总DNA含量的减少和乳钠浓度的增加。后者表明乳腺上皮细胞之间的紧密连接打开，这通常发生在乳腺的去分化和退化过程中。这表明PRL至少部分地通过抑制上皮细胞损失和维持细胞分化来维持乳汁合成。相比之下，生长激素缺乏只导致产奶量小幅下降（24%），对牛奶的主要成分或牛奶钠浓度或总乳腺DNA含量没有影响。然而，当使动物缺乏PRL和GH时，奶量沿着显著减少（88%），同时所有主要奶成分的产量也显著减少，证实了我们先前的发现，即PRL和GH是奶合成的主要调节剂。最近的研究表明，GH对乳腺生长有直接作用，但其对乳汁分泌的作用被认为是通过胰岛素样生长因子-I（IGF-I）间接介导的。因此，我们通过诱导PRL和GH缺乏48小时来抑制泌乳，然后尝试通过全身或局部油基植入物给药GH来重新启动泌乳。油基GH植入物在刺激治疗（但不是对侧，对照）腺体中的乳汁分泌方面与全身GH治疗一样有效。因此，GH确实直接作用于乳腺以刺激乳汁合成，尽管这并不排除GH通过刺激局部IGF-I产生而起作用的可能性。然而，我们以前无法模拟这种效果的GH使用IGF-I或各种IGF-I类似物。因此，生长激素刺激产奶的作用机制需要进一步研究。
Both PRL and GH play a role in maintaining lactation in the rat, although GH can only maintain pup weight gain at around 50% of the control value, whereas PRL can maintain weight gain close to 90% in the absence of GH. In this study we examined the effects of PRL and GH deficiency (using bromocriptine and an antiserum to rat GH) on milk yield and composition in lactating rats. Treatment with bromocriptine to suppress PRL secretion for 48 h led to a 57% decrease in milk yield with a concomitant decrease in milk protein and lactose yields, but no decrease in fat output. This led to the production of milk with a lower lactose concentration but increased concentrations of protein and particularly fat (increased 100%), which suggests that GH serves an auxiliary role by maintaining an energy-rich milk for the neonate when PRL secretion is reduced. This decrease in milk synthesis was accompanied by decreases in total mammary DNA content and increased milk sodium concentrations. The latter indicates the opening of tight junctions between mammary epithelial cells, which normally occurs during dedifferentiation and involution of the mammary gland. This suggests that PRL maintains milk synthesis at least in part by inhibiting epithelial cell loss and maintaining cellular differentiation. A deficiency in GH, by contrast, caused only a small decrease (24%) in milk yield and had no effect on the major constituents of milk or on milk sodium concentrations or total mammary DNA content. When animals were made deficient in both PRL and GH, however, there was a further marked decrease (88%) in milk volume along with the yields of all major milk constituents, confirming our previous findings that PRL and GH are the major regulators of milk synthesis. Recent studies have indicated that GH exerts direct effects on mammary gland growth, but its actions on milk secretion have been proposed to be mediated indirectly via insulin-like growth factor-I (IGF-I). We, therefore, inhibited lactation by inducing PRL and GH deficiency for 48 h and then attempted to reinitiate it by administering GH either systemically or by local oil-based implants into the mammary gland.Oil-based GH implants were as effective in stimulating milk secretion in the treated (but not contralateral, control) gland as was systemic GH treatment. Thus, GH does act directly on the mammary gland to stimulate milk synthesis, although this does not rule out the possibility that GH acts by stimulating local production of IGF-I. However, we have previously been unable to mimic this effect of GH using IGF-I or a variety of IGF-I analogs. The mechanism of action of GH in stimulating milk production thus requires further study.