Urinary levels of immunoreactive NH2-terminal of pro-opiomelanocortin in patients with malignant pulmonary disease.

Urinary levels of immunoreactive (IR) human NH2-terminal (hNT) of pro-opiomelanocortin were measured in 43 patients with various cell types of lung cancer (19 squamous cells, 12 oat cells, 2 large cells, and 10 adenocarcinoma), 32 patients with benign lung disease, two patients after hypophysectomy, and in 23 healthy volunteers. Lung cancer patients were divided into two subgroups according to the stage of the disease: 22 patients had "limited", and 21 patients "extensive" disease. Urinary and plasma levels were measured in 9 patients with lung cancer before and after radio- and chemotherapy or surgery. Urine samples were dialyzed and IR hNT material was extracted by Sep Pak C-18 cartridges using a propanol-2/TFA solvent system. The plasma and urinary IR hNT levels of the normal controls were 124 +/- 25 pg/ml and 47.8 +/- 14.5 pg/mg creatinine, respectively. The plasma levels of IR hNT were elevated (greater than mean + 2SD) in 65% of our patients with histologically proven lung cancer (422 +/- 775, mean +/- SD, pg/ml). The highest incidence of an elevated plasma level of IR hNT was found in oat cell carcinoma (83%). Elevated plasma IR hNT occurred in 66% of the patients with benign pulmonary disease (246 +/- 141 pg/ml, N.S.). In cancer patients with "limited" disease we found levels of 226 +/- 143 pg/ml and in patients with "extensive" disease 627 +/- 1074 pg/ml (N.S.). The urinary IR hNT level in lung cancer patients was 186 +/- 337 pg/mg creatinine and 81% of our patients had elevated levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary molecular forms of human N-terminal of proopiomelanocortin: possible deglycosylation and degradation by the kidney.

The NH2-terminal fragment (hNT) of proopiomelanocortin is found predominantly as one molecular form of apparent mol wt of 12K in the circulation. Since the kidney may play an important role in the elimination and degradation of proopiomelanocortin-related peptides, we analyzed the urinary forms of immunoreactive hNT (IR-hNT) by molecular sieving and carbohydrate affinity (Concanavalin A-agarose) chromatography. RIA specific for the amino terminal portion and for the gamma 3-MSH (carboxy-terminal portion of hNT) were used in these studies. Molecular sieve chromatography revealed several forms of IR-hNT in the urine from normal subjects, patients with Nelson's syndrome, and patients with ectopic ACTH-secreting tumors. A considerable decrease in IR-hNT and IR-gamma 3-MSH was found in the urine of a patient with ACTH deficiency and normal subjects during glucocorticoid suppression. In urine from normal subjects and a patient with lung cancer not causing Cushing's syndrome, the majority of amino-terminal IR-hNT (66-83%) had apparent mol wts of 3-4K, 6-7K, and 8-10K, and did not cross-react with the gamma 3-MSH antiserum. Ten to nineteen percent of the total IR-hNT was eluted in the position of authentic hNT and reacted with the gamma 3-MSH RIA. In patients with Nelson's syndrome and those with ectopic ACTH syndrome, almost no intact hNT (less than 7% of the total) was present in urine; most of the IR-hNT appeared in the elution volumes with an apparent mol wt of 8-10K. In addition, smaller forms (6-7K and 3-4K) of hNT were also detected in the urine of these patients. The major form of urinary IR-gamma 3-MSH exhibited an apparent mol wt of 7-8K and did not correspond to any of the peaks of IR-hNT. Carbohydrate affinity chromatography (Concanavalin A-agarose) of smaller forms of IR-hNT revealed weak affinity to the lectin, which suggests loss of the carbohydrate moiety during renal excretion. We conclude that hNT in urine is present in extensively cleaved forms and that deglycosylation may be an important step in hNT degradation. These results support a role for the kidney in the catabolism of hNT.