Separation of early and late responses of adipose tissue to growth hormone.

GH produces a variety of effects in adipose tissue obtained from hypophysectomized rats. A specific antiserum to rat GH produced in a rhesus monkey was used as a tool to study the relationship of these responses to each other. In all, five different metabolic responses produced by adding 1 microgram/ml rat GH to segments of epididymal fat obtained from hypophysectomized rats were studied. Three of these, stimulation of [U-14C]glucose oxidation to 14CO2, stimulation of L-[1-14C]leucine oxidation to 14CO2, and inhibition of epinephrine-induced lipolysis, are insulin-like. They begin after lag periods of about 25, 35, and 15 min, respectively, and disappear by about 180 min. The addition of antiserum simultaneously with the hormone or within the first 10 min thereafter blocked all three responses. When added more than 10-15 min after GH the antiserum failed to block insulin-like responses measured 30-60 min later, even if the response was prolonged into the fourth hour by adding actinomycin D along with GH to block the cellular restorative processes. Thus, insulin-like effects, once triggered, appear to be independent of the continued presence of the hormone. Furthermore, differences in the lag periods required for each insulin-like response appear to be due to the times required to carry out postreceptor events. Delayed lipolysis, observable in the presence of theophylline, becomes evident only after at least 1 h and can also be blocked by the simultaneous addition of hormone and antiserum. The tissue-hormone interaction which initiates this effect occurs rapidly, and its appearance in the second hour of incubation cannot be blocked if the antiserum is added 5 min after GH. This response persists for at least 5 h. The addition of antiserum 60 or 120 min after GH aborts the lipolytic response, but only after a delay of about 1 h. Thus, unlike the insulin-like responses, the accelerated rate of lipolysis requires the continued presence of the hormone to persist. After the insulin-like effects of GH have run their course, a second insulin-like response cannot be initiated for many hours by a second exposure to GH. The initial exposure to GH renders tissues refractory to the insulin-like action of the hormone. The induction of refractoriness, as measured in the fourth hour, can be blocked by the addition of antiserum simultaneously with GH or as much as 60 min after the hormone, suggesting that prolonged contact between tissue and hormone is required. These studies suggest that GH interacts with adipose tissue in at least three different ways, and that not all of the various responses of tissue to hormone are causally related.