Comparison between bioactivity and immunoreactivity of serum prolactin in uraemia.

The lactogenic potency of sera from 24 male uraemic patients on regular haemodialysis and 14 control subjects was measured by Nb2 node rat lymphoma cell bioassay, and was compared to serum prolactin levels measured by radioimmunoassay. Sera with immunoreactive growth hormone levels exceeding 5 ng/ml were excluded from comparisons. The uraemic patients had a higher serum immunoreactive prolactin (48.2 +/- 10.5 ng/ml) than controls (13.3 +/- 1.3 ng/ml (P less than 0.01). Similarly the lactogenic potency of uraemic serum was higher than that of the control sera (25.5 +/- 3.9 vs 12.6 +/- 1.4 ng/ml, P less than 0.02). The ratio of immunoreactive serum prolactin to the lactogenic potency of the serum was significantly higher in the uraemic group (1.80 +/- 0.14 vs 1.10 +/- 0.10, P less than 0.01) suggesting decreased bioactivity of prolactin in uraemic serum. To examine whether low molecular weight inhibitory molecules were responsible for this discrepancy, the lactogenic potency of 8 uraemic sera was studied before and after 4 h of dialysis against 1 litre of haemodialysis medium. Two of the eleven sera studied showed a significant increment in lactogenic potency after dialysis (47% and 57%). We conclude that there is a disparity between the bioactive and the immunoreactive serum prolactin concentrations in patients with chronic renal failure and that a dialysable factor may be partly responsible for this discrepancy in some cases.

Effects of cysteamine on pituitary, MTTW15 tumor, and serum prolactin levels measured by rat lymphoma cell bioassay and radioimmunoassay.

Cysteamine (CSH), a sulfhydryl compound, reduces both serum and anterior pituitary (AP) PRL measured by RIA. We have used the Nb2 lymphoma cell bioassay (BIO) for PRL to evaluate possible CSH-related changes in PRL levels in sera and tissues of male and MtTW15 mammosomatotropic tumor-bearing female rats. Experimental animals received a single sc injection of CSH (300 mg/kg), and samples were collected 0.5-24 h later. Since CSH and serum from CSH rats were toxic in BIO, samples were dialyzed before assay. All samples were evaluated for PRL and GH by RIA as well. A significant decrease (P less than 0.05) in BIO serum PRL was evident in male rats 0.5 h after CSH; levels remained low for 24 h. Serum PRL by RIA was significantly depressed at 4 h but not at 0.5 h or 24 h. PRL in AP extracts was decreased (60-90%) at all times by BIO and RIA. Significant decreases of BIO- and RIA-detectable PRL were recorded in serum and tissues (AP and tumors) at 4 h in tumor rats. Sequentially bled (0.5-4 h) CSH-treated tumor-bearing rats showed 50% and 80% reductions in serum PRL at 1 and 4 h by both BIO and RIA. CSH had no effect on GH levels in sera and tissues of any animal studied at any time interval. Our results substantiate earlier reports on CSH-induced decreases in RIA-detectable PRL. They show that such changes cannot be attributed to assay effects alone, as significant decreases in circulating and stored PRL (both AP and tumor) were evident by BIO. Results with tissue extracts were the most dramatic. They suggest an action of CSH or a metabolic intermediate with stored PRL which reduces both extractable PRL and hormone release. Such an effect of CSH on PRL extraction has been suggested by others. Whatever the mechanism, it appears to be relatively specific, since GH cells were not affected.

Effect of MtTW15 mammosomatotropic tumors on pancreatic islet hormones.

The effects of hypersecretion of growth hormone and prolactin on islet endocrine cells have been studied by radioimmunoassays, immunocytochemistry, and morphometry in randomized samples of pancreata from MtTW15 mammosomatotropic tumor-bearing and control rats. The randomized sampling procedure, validated by immunoassays, allowed evaluation of both hormone content (immunoassay) and endocrine cell population (immunocytochemistry) on samples derived from the same origin. Hyperinsulinemia (2x) and non-fasting hypoglycemia in 10-wk-tumor rats were normalized 3 wk after tumor removal. Pancreatic weight was doubled, but proportional to body weight increases. Islet/pancreas ratio was constant (1.29 +/- 0.05%) and the same in tumor, tumor-removed, and control animals, but average islet dimensions were increased by 30% and average area doubled in tumor animals. Frequency analysis showed fewer small (less than 70 micrometers) and more large (greater than 140 micrometers) islets in tumor animals, but no change in average islet shape shown by average axis ratios of 1.4 in all groups. Pancreatic content of insulin and glucagon was doubled, while that of somatostatin was constant. These changes were not completely reversed in tumor-removed animals. Similarly, a significant doubling in islet-derived mass was mainly due to a doubling of the B-cell mass as the average proportion of endocrine cells per islet shifted from 66%, 26%, and 18% to 81%, 18%, and 3% for B-, A-, and D-cells of control and tumor-bearing rats, respectively. Immunocytochemically detectable insulin was found in duct cells of tumor animals, but not controls. Whether such cells represent a functional reserve remains to be determined.