Flint D J, Vernon R G
Hannah Research Institute, Ayr, UK.
J Endocrinol. 1998 Feb;156(2):299-305. doi: 10.1677/joe.0.1560299.
Exogenous GH is used extensively in the USA to stimulate milk production in dairy cattle but its effectiveness is reduced in undernourished animals. It has been proposed that GH increases milk yield by stimulating IGF-I secretion and that this IGF-I-response is nutritionally sensitive and thus acts as a 'sensor' of energy balance. To investigate this possibility, we placed lactating rats on three planes of nutrition, ad libitum, 50% or 25% of ad libitum for 48 h. Subgroups of these animals were treated for 48 h with bromocriptine, to suppress prolactin secretion, and anti-rat GH, to neutralize GH action. From 24 to 48 h some of the treated animals were assessed for their milk yield response to prolactin or GH. Food restriction reduced milk yield in control rats by approximately 50% and was accompanied by a catabolic state, as judged by lipid mobilization from adipose tissue and by low concentrations of serum insulin, IGF-I, triiodothyronine and thyroxine, and increased serum nonesterified fatty acid concentrations. In animals fed ad libitum, anti-rat GH plus bromocriptine treatment produced an 80% decrease in milk yield and a dramatic fall in the activity of acetyl-CoA carboxylase in mammary tissue. GH was able to stimulate milk yield when given from 24 to 48 h; however, its effectiveness decreased progressively as food intake was reduced. The milk yield response to GH was accompanied by an increase in serum IGF-I concentrations and this response also decreased progressively with reduction of food intake, consistent with the hypothesis that IGF-I determines the milk yield response to GH and thus regulates GH action on the mammary gland in a nutritionally dependent fashion. However, the milk yield response to prolactin and the milk yield of control rats decreased in line with food intake without any changes in serum IGF-I concentrations. This clearly indicates that factors other than IGF-I are responsible for restricting milk yield. In order to assess other possible candidates for this role, we monitored serum glucose, non-esterified fatty acids, insulin triiodothyronine and thyroxine concentrations, but found no evidence for any simple relationship between these parameters and the milk yield response to prolactin and GH. Surprisingly we found that the ability of GH or prolactin to prevent epithelial cell loss in in the mammary gland was completely insensitive to nutrient intake, despite the fact that IGF-I is considered to be an important survival factor for mammary epithelial cells. Finally, we also demonstrated that, at least during short-term food restriction, the lactating rat is capable of mobilizing significant amounts of lipid from adipose tissue, such that it could provide the total output of triglyceride in milk, which is much greater than has previously been proposed.
在美国，外源性生长激素被广泛用于刺激奶牛产奶，但在营养不良的动物中其效果会降低。有人提出，生长激素通过刺激胰岛素样生长因子-I（IGF-I）的分泌来提高产奶量，并且这种IGF-I反应对营养敏感，因此可作为能量平衡的“传感器”。为了研究这种可能性，我们将泌乳大鼠置于三种营养水平，即自由采食、自由采食的50%或25%，持续48小时。这些动物的亚组用溴隐亭处理48小时以抑制催乳素分泌，并用抗大鼠生长激素中和生长激素的作用。在24至48小时期间，对一些处理过的动物评估其对催乳素或生长激素的产奶量反应。食物限制使对照大鼠的产奶量降低了约50%，并伴有分解代谢状态，这可通过脂肪组织的脂质动员以及血清胰岛素、IGF-I、三碘甲状腺原氨酸和甲状腺素浓度较低，以及血清非酯化脂肪酸浓度升高来判断。在自由采食的动物中，抗大鼠生长激素加溴隐亭处理使产奶量降低了80%，乳腺组织中乙酰辅酶A羧化酶的活性急剧下降。在24至48小时给予生长激素能够刺激产奶量；然而，随着食物摄入量的减少，其效果逐渐降低。对生长激素的产奶量反应伴随着血清IGF-I浓度的增加，并且这种反应也随着食物摄入量的减少而逐渐降低，这与IGF-I决定对生长激素的产奶量反应并因此以营养依赖方式调节生长激素对乳腺作用的假设一致。然而对催乳素的产奶量反应以及对照大鼠的产奶量随食物摄入量下降，而血清IGF-I浓度没有任何变化。这清楚地表明，除IGF-I之外的其他因素导致产奶量受限。为了评估可能起此作用的其他候选因素，我们监测了血清葡萄糖、非酯化脂肪酸、胰岛素、三碘甲状腺原氨酸和甲状腺素浓度，但未发现这些参数与对催乳素和生长激素的产奶量反应之间存在任何简单关系的证据。令人惊讶的是，我们发现生长激素或催乳素防止乳腺上皮细胞丢失的能力对营养摄入完全不敏感，尽管IGF-I被认为是乳腺上皮细胞的重要存活因子。最后，我们还证明，至少在短期食物限制期间，泌乳大鼠能够从脂肪组织中动员大量脂质，使其能够提供乳汁中甘油三酯的总输出量，这比之前提出的要多得多。
