Synthetic human gastrin 17-I (MG) and an analogue, [Leu15]gastrin-17-I (LG), were radiolabeled with Na125I by Iodo-Gen, EnzymoBead, and chloramine-T methods, and the characteristics of the radiolabeled peptides were determined. When 125I-MG was iodinated by chloramine-T, its biological activity and its binding activity were almost abolished, whereas the biological activity of 125I-LG, iodinated by either of the methods, and of 125I-MG, iodinated by Iodo-Gen and EnzymoBeads, was not significantly affected. The kinetics, affinity, and specificity of binding of 125I-MG, iodinated by Iodo-Gen, to crude and purified membranes from rat fundic mucosa were examined and found to be similar to that for 125I-LG. Age-associated changes in the number and affinity of gastrin receptors (GR) on the crude membranes of gastrointestinal mucosa of rats was also examined. Significantly fewer GR were observed on the crude membranes of fundic mucosa of aged (24 mo old) compared with young (3- and 6-mo-old) rats. In addition, specific gastrin-binding sites (4.7 +/- 0.9 fmol/mg prot) with low affinity (Kd = 3.7 +/- 1.2 nM) were observed in the antrum of aged rats, the significance of which is not understood. There were, however, no differences in the number and characteristics of GR in other regions of the intestine of old and young rats. The presence of GR was additionally assessed in cell lines of gastrointestinal cancers from humans, mice, and hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy specimens of 55 human mammary carcinomas (38 primary and 17 metastatic) were assayed for prolactin receptors (PrlR). Prolactin bound specifically to 32 (58%) of the tumor biopsy specimens. The apparent Kd for PrlR in individual tumors ranged from 15 pM to 2.3 nM (mean 600 pM, n = 5) and the concentration of PrlR ranged from 0 to 44.5 fmoles/mg protein. Estrogen receptors (ERP) were also detected in 28 of the 32 tumors which had PrlR. Overall, there was no correlation between PrlR and ERP. However, the mean concentration of PrlR was significantly higher (p less than 0.01) in tumors with 6-100 fmoles/mg protein ERP (approximately 13 fmoles PrlR) than in tumors with either less than 6 or greater than 250 fmoles ERP (4.0 +/- 0.4 and 6.5 +/- 1.8 respectively fmoles PrlR). Analysis of PrlR concentration as a function of patient age also showed no overall correlation, but the mean PrlR in tumors from women aged 60-70 was significantly higher (p less than 0.01) than in those from either younger or older women. A higher concentration of PrlR was observed in tumors which were classified histologically as medium or well differentiated (6.1 +/- 1.2 and 11.1 +/- 2.1, respectively) than in those classified as poorly differentiated (3.3 +/- 1.2) (p less than 0.03). There was a negative correlation between PrlR concentration and membrane yield from the tumors (r = 0.43, p less than 0.02). The membrane yield correlated with the ratio of tumor cells to stroma (histologically) (r = 0.63, p less than 0.001). In tumors from 12 patients with metastatic disease on whom follow up after endocrine-related therapy was available, the mean PrlR concentration was significantly higher in the non-responding group (8.2 +/- 3.0) than in the responding group (3.4 +/- 4.2, p = 0.05).

No abstract

No abstract