Growth Hormone Maintains Its Own Receptors in Rat Adipocytes*

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Abstract
Hypophysectomy decreased the capacity of adipocytes isolated from epididymal fat to bind [125I]human GH ([125I]hGH) specifically without changing the apparent affinity for hGH. Specific binding of hGH by adipocytes of both normal and hypophysectomized rats appeared saturated when incubated with 75-80 ng/ml or higher concentrations of GH regardless of whether binding was studied for 2 h at 37.degree. C or for 16 h at 0.degree. C. Maximum binding of hGH by normal adipocytes was approximately 0.45 ng/106 cells, and that by adipocytes of hypophysectomized rats ranged from 0.15-0.25 ng/106 cells. In cells of both normal and hypophysectomized rats, only 25-30% of the hormone specifically bound at 37.degree. C was removed by digestion with trypsin, and about 75% was displaced by incubation with 5M magnesium chloride, suggesting that these adipocytes internalized a significant fraction of bound hormone and that hypophysectomy did not alter the extent of internalization. Previously bound hormone was lost from normal adipocytes with a half-time of about 32 min and from adipocytes of hypophysectomized rats with a half-time of about 45 min, suggesting that hypophysectomy slowed the rate of processing bound hormone. To determine which pituitary hormone(s) might be required to maintain GH binding, we measured the binding of [125I]hGH at 3 or 30 ng/ml by fat cells prepared from hypophysectomized rats after various treatment regimens. Administration of bovine GH ip at a dose of 10 .mu.g/rat every 4 h for 24 h doubled the binding of [125I]hGH by adipocytes prepared 4 h after the last injection. Similar results were obtained in fat cells examined 4 h after only one injection of 60 .mu.g bovine GH to rats hypophysectomized 2-4 weeks previously. When binding was measured 16-24 h after GH administration, there was no apparent effect on restoration of binding even after treatment with 10 .mu.g GH/day for up to 6 days, suggesting that the effects of GH in maintaining receptor number are transient. In accord with the apparently short-lived ability of GH to maintain its receptors on fat cells, GH binding was significantly reduced in adipocytes obtained from both hypophysectomized and sham-operated rats as early as 4 h after surgery, and by 8 h after surgery, declined to a level as low as that in adipocytes of chronically hypophysectomized rats. Twenty-four hours after surgery, GH binding by cells of sham-operated animals returned to normal. Fasting for 24 h also reduced GH binding by adipocytes of normal rats to a level comparable to that in adipocytes of fed hypophysectomized animals. Extension of the period of fasting to 48 h produced a significant further decline in GH binding by adipocytes of both normal and hypophysectomized rats. Since fasting and surgical stress are known to inhibit GH secretion, we suggest that the ability of fat cells to bind GH varies under normal physiological circumstances and is dependent on GH secretion, although other factors must also be involved. The data suggest that GH receptors in adipocytes are highly labile and require ongoing GH secretion for their maintenance.