James A. Pittman

Utility of the Radioimmunoassay of Serum Thyrotrophin in Man

Abstract The normal human serum thyrotrophin (TSH) measured by a double antibody radioimmunoassay was 3.9 ± 2.0 (SD) µunits/ml. It was markedly elevated in 61 patients with primary hypothyroidism a...

THYROXINE ANTAGONISM BY PARTIALLY IODINATED THYRONINES AND ANALOGUES

A decade ago several laboratories were concerned with inhibition of thyroxine (T4) shown by a variety of synthetic compounds vaguely related to the hormone. These were mostly derivatives of 3,5-diiodo-4-hydroxybenzoic or iodophenoxyacetic acids. In general, high dosages were required,’ involving molar ratios of antagonist to T4 of from 250: 1 to 2000: 1. With the recent availability of synthetic 3-iodothyronine (TI), 3,3’-diiodothyronine (3,3’-T~), and 3,3’,5’-triiodothyronine (3,3’,5’-T3), as well as their acetic and propionic acid analogues, various laboratories2 including ours have found them to possess essentially no metabolism-stimulating properties (unpublished observations). This aroused our interest in the possibility that these unusual iodothyronines would interfere with the actions of T4 and 3,5,3’triiodothyronine (TRIT, T3 ,3 ,5 ,3’-T3).8

A study of the thyroglobulin, thyroidal protease and iodoproteins in two congenital goitrous cretins☆

Abstract Detailed studies of thyroid functions were carried out in two adult goitrous cretins who were siblings. Both patients had high levels of serum protein-bound iodine, only a fraction of which could be accounted for as iodothyronines. The major circulating iodoprotein possessed many physical characteristics resembling those of serum albumin. Data are presented to indicate that this iodoprotein was not related to thyroglobulin as a precursor or as a degradation product but was rather the product of a collateral pathway of iodine metabolism in the thyroid. Thyroglobulin isolated from these patients showed normal electrophoretic mobility, sedimentation and solubility. The protease from their thyroid glands was able to hydrolyze the thyroglobulin from those glands in an apparently normal manner. The etiology of this disorder may be related to a reduced level of an enzyme in thyroglobulin synthesis with consequent glandular hypertrophy and increased synthesis of other thyroidal iodoproteins.

Purification of Bovine Thyroid-Stimulating Hormone by Solubility Fractionation with Ammonium Sulfate∗:

Summary Solubility fractionation of relatively crude TSH with ammonium sulfate was investigated as a means of purifying the hormone. The results obtained with three variations in solubility fractionation techniques using decreasing concentrations of ammonium sulfate demonstrated that each method yielded a 5- to 7-fold purification of the 0.49 to 0.84 U/mg starting material. Total recovery of TSH was 90-100%. Recoveries in the high potency fractions were 60-80% when TSH was extracted with ammonium sulfate or recovered by fractional precipitation and 25-35% when batch eluted from diethylaminoethyl (DEAE) cellulose. Solubility fractionation appears to be a simple and rapid method for the purification of TSH to 4-6 U/mg which may be adequate for most purposes. Highly purified TSH may then be obtained by standard column chromatography with DEAE-cellulose.

Endocrine Effects of Sulfoxone and of Two Nitriles as Compared with Amphenone.

Summary A sulfone, sulfoxone, and 2 nitrile steroid analogues, SC-3402 and SC-4473, have been tested in female rats for endocrine effects and compared with amphenone for reference. None of the 3 substances caused adrenal enlargement similar to that seen in the amphenone-treated animals. SC-4473 was markedly estrogenic. This substance represents the first nitrile to be shown to possess estrogenic activity in the rat.