Stimulation of the circulating levels of glycoprotein hormone alpha-subunit after combined administration of a luteinizing hormone-releasing hormone (LHRH) agonist and flutamide in patients with cancer of the prostate.
To ascertain whether the immunoreactive luteinizing hormone (LH) levels measured following the combined treatment may represent cross-reaction of the LH antiserum with LH subunits, we have examined the effects of therapy on the serum levels of free alpha- and free LH-beta-subunits in intact, castrated, and estrogen-treated patients. In previously untreated patients receiving the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide in association with the pure antiandrogen Flutamide, serum-free alpha-subunit levels were stimulated from 0.09 +/- 0.02 to 3.10 +/- 0.84 ng/ml after 5 days, and declined slowly afterwards to 1.33 +/- 0.20 ng/ml after 3 months of combined treatment. In patients pretreated from 12 to 24 months (17.5 +/- 1.0 months) with diethylstilbestrol (DES) prior to receiving the combined therapy, free serum alpha-subunit concentration followed a similar pattern, rising from 0.22 +/- 0.03 to 1.78 +/- 0.28 ng/ml after 15 days of combined treatment, and declining thereafter to 0.81 +/- 0.10 ng/ml after 3 months. Free LH-beta-subunits were below the detection limit in most previously untreated patients and in all DES-treated patients. After correcting for the cross-reactivity of the alpha-subunit in the LH RIA, immunoassayable LH serum levels in previously untreated patients were only slightly reduced from 0.81 +/- 0.06 ng/ml before the onset of the combined treatment to 0.52 +/- 0.05 ng/ml after 3 months. On the contrary, bioactive serum LH levels were drastically inhibited from 0.43 +/- 0.04 to 0.03 +/- 0.01 ng/ml after the same duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000726:Androgen Antagonists / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use*; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy; D002369:Castration; D005485:Flutamide / Q000627:therapeutic use*; D015292:Glycoprotein Hormones, alpha Subunit; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000097:blood*; D010908:Pituitary Hormones, Anterior / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy; D013268:Stimulation, Chemical; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D000726:Androgen Antagonists; D000813:Anilides; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C019176:Tryptal; D005485:Flutamide; D007986:Luteinizing Hormone