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.

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