Somatogenic Receptors of Rat Liver: Regulation by Insulin*

Abstract

Somatogenic (i.e. GH) receptors have been studied on liver microsomal membranes from male and female rats. Tracer bovine GH was displaced from its binding sites by GHs of various species, but was displaced only weakly by PRLs. Specific bovine GH binding was 3.5-fold higher to female rat liver membranes than to membranes from males. Streptozotocin-induced diabetes significantly reduced binding, by 80% in females and 50% in males, while insulin therapy to normalize weight gain reversed the decrease in binding. Competitive binding curves were consistent with two independent classes of binding site: low affinity sites with K equal to 0.5 nm-1 in both sexes, and high affinity sites with K equal to 12.1 nm-1 in males and 21.4 nm-1 in females (P less than 0.001). The addition of excess ovine PRL caused a substantial loss of high affinity binding with little loss in the low affinity region, suggesting a weak somatogenic role for ovine PRL. In diabetic animals, low affinity sites were unchanged from normal, while high affinity sites were decreased in number, with no change in affinity, and restored on insulin therapy. Serum immunoreactive rat GH levels were the same in normal and diabetic, male and female animals. These studies suggest that the apparent hepatic resistance to GH seen in diabetes when liver somatomedin release is low despite normal serum GH might be explained by the loss of GH receptors in this condition.

Adrenal involvement in the diabetes-induced loss of growth hormone and prolactin receptors in the livers of female rats

“…Regulation of rat liver GH receptors by testosterone has not been documented, although it has been reported that females have more receptors than males [1,12,13]. Our studies confirm that testosterone decreases PRL receptors, and they establish a similar role for testosterone on GH binding in the livers of female rats.…”

“…Although the nonspecific binding of bGH tracer was high relative to the specific binding, this figure is comparable to that seen in other published studies of bGH binding to microsomal membranes [1,14], homogenates [5] and hepatocyte pellets [12]. The bGH for iodination (S-…”

“…Comparison with control animals p < 0.05. Comparison with diabetic animals sured on 200 gg of membrane protein, using bovine GH (bGH) and ovine PRL (oPRL) respectively as radioligands as reported earlier [1,2]. Briefly, for either receptor type incubations were performed at 22 °C in 1.5 ml polystyrene centrifuge tubes for 16 h in a final volume of 0.3 ml of Tris-HC1 (25 mmol/1), CaCI2 (10 retool/l) buffer containing 0.1% bovine albumin, pH 7.4.…”

“…We have previously reported that both growth hormone (GH) and prolactin (PRL) receptors in liver microsomal membranes decreased in number, but not affinity, in female rats with experimental diabetes induced by streptozotocin [1,2]. Insulin treatment restored these receptors to normal levels.…”

“…In contrast to prolactin receptors, little is known about the regulation of G H receptors in rat liver by sex steroids, except that livers from female animals are known to have more receptor sites that those from males when measured in either whole hepatocytes [12] or microsomal membrane preparations [1,13].…”