A radioimmunoassay for rabbit luteinizing hormone (rLH) in which rLH shows no significant cross-reaction with human LH (hLH) or human chorionic gonadotropin (HCG) was employed to test for the existence of a short-loop feedback for LH in the rabbit. Two weeks after castration, hCG and hLH were administered intravenously to rabbits, and the effects on circulating rLH were measured. Purified hLH (10 ng or 100 IU) produced significant depression of blood rLH within 30-60 min of intravenous injection. Saline administered to the same animals produced no changes in rLH. Injection of hCG (2,000 IU) under the same conditions also produced a significant fall in rLH. However, hCG administered to rabbits castrated 6 wk prior to study failed to suppress endogenous rLH. These data demonstrate, by direct radioimmunoassay quantification of blood hormones, the existence of a short-loop negative feedback for LH in the rabbit. They also suggest that the sensitivity of the short-loop changes with time after castration.

No abstract

Free alpha subunit chains of the glycopeptide pituitary hormones have been found in the sera of normal subjects and postmenopausal women. To ascertain whether the alpha subunit of LH is directly secreted by the pituitary or formed as a result of degradation of intact LY in the periphery, alpha subunits and intact LH were measured by radioimmunoassay in human volunteers after LRF stimulation and purified LH infusion. In 4 subjects a loading dose of 90 IU, followed by the infusion of 22.5 IJ of purified human LH over 30 min, produced peak serum LH levels of 41 mIU/ml but no change in alpha subunit levels of 35 IU of purified human LH to an additional 4 subjects, produced peak LH levels of 8* mIU/ml, but again, no change in alpha subunits. In the same two groups of subjects 100 mug of LRF produced peak LH levels of 25 mIU/ml and 75 mIU/ml, respectively, with significant alpha subunit elevations at 20 min of 1.7 ng/ml and 2.7 ng/ml, respectively. In separate groups of men LRF was administered over a wide dose range of 1 to 3,000 mug and LH and the alpha subunit measured. A dose-response curve existed over the entire LRF dose range for blood LH; no minimum or maximum plateaus were observed over the range studied. However, the alpha chain response appeared to reach a maximal plateau at a dose of 100 mug of LRF. The results are compativle with the hypothesis that the alpha subunits appearing in the peripheral circulation in response to LRF are due to secretion by the anterior pituitary and not due to peripheral degradation of intact secreted LH.

No abstract

Because administration for 1 week of the GnRH antagonist Nal-Glu GnRH had been shown to decrease FSH secretion from supranormal to normal in men with gonadotroph adenomas, we investigated the effect of prolonged administration of Nal-Glu on the size of gonadotroph adenomas. To quantitate the effect of Nal-Glu GnRH on gonadotroph adenoma size, we first developed a technique for calculating adenoma volume. The technique involved collecting magnetic resonance (MR) imaging data from each adenoma at 1-mm slice intervals in the coronal, axial, and sagittal views and using the Softvu computer program to calculate adenoma volume from the MR data. The precision of this technique, as judged by the coefficients of variation of the calculations of the same view of the same study three times, was 1.7%, 1.0%, and 1.0% for each of three studies. When Nal-Glu GnRH (5 mg, sc, every 12 h) was self-administered for 3-12 months to five men with gonadotroph adenomas and supra-normal serum FSH concentrations, the serum FSH concentrations decreased to normal or below normal for the entire treatment period. Adenoma size, however, did not change during treatment in any of the five men. We conclude that calculating pituitary adenoma volume from MR data using the Softvu computer program is a highly reproducible technique, but that Nal-Glu GnRH is not an effective treatment for reducing gonadotroph adenoma size. The failure of Nal-Glu to reduce adenoma size despite its success in reducing FSH secretion suggests that FSH secretion from gonadotroph adenomas is dependent on endogenous GnRH, but growth of gonadotroph adenomas is not.

I T HAS been noted by Peoples and Guttmann, ' Myerson," Nathanson" and others that benzedrine has a stimulating effect psychologically. A feeling of exhilaration and a sense of increased energy and capacity for work were noted in adults. Sargant and Blackburn! investigated the effects of benzedrine on 48 adult patients in a mental hospital, using Cattell's intelligence tests, and noted an 8% improvement in the test scores. The unpleasant reactions were infrequent in adults and no serious toxic effects were noted.Researches are under way, in the New Jersey State Home for Boys, to determine the effect of benzedrine (benzyl methyl carbinamine) on psychological tests, school tests and school progress. The present report concerns itself solely with the effects of the drug on the New Stanford Achievement Tests total (average) score. Ninety-six boys between the ages of 10 and 17, and of varying mental levels, received 219 tests. Forty-six of them were used as controls and received no benzedrine at any time. The boys studied constituted behavior problems and had been previously committed by court as being juvenile delinquents. Procedure • We wish to thank Mr. R. W. Webb of the Smith, Kline and French Laboratories for supplying the Benzedrine Sulfate• •• From the New Jersey State Home for Boys and the

We have attempted to determine whether blood concentrations of the alpha chains of TSH arise by direct pituitary secretion of alpha chain or by degradation of the intact hormone after secretion. Highly purified human TSH was administered by infusion to euthyroid volunteers; blood TSH concentrations were raised to 36 muu/ml. After TSH infusion, circulating blood alpha chain concentrations did not change. The same volunteers received an infusion of TRH which stimulated pituitary secretion of TSH, raising blood concentrations to 15 muu/ml in one series of subjects and to 23 muu/ml in a second series. After TRH, blood concentrations of alpha chain increased from undetectable to over 400 pg/ml. We conclude that alpha subunits of TSH are directly secreted by the pituitary gland and are not formed by degradation of intact TSH in the peripheral circulation.

S U M M A R YWe have attempted to determine whether blood concentrations of the a chains of TSH arise by direct pituitary secretion of a chain or by degradation of the intact hormone after secretion. Highly purified human TSH was administered by infusion to euthyroid volunteers ; blood TSH concentrations were raised to 36 pu/ml. After TSH infusion, circulating blood c1 chain concentrations did not change. The same volunteers received an infusion of TRH which stimulatedpituitary secretion ofTSH, raising blood concentrations to 15 pu/ml in one series of subjects and to 23 pulml in a second series. After TRH, blood concentrations of a chain increased from undetectable to over 400 pg/ml. We conclude that a subunits of TSH are directly secreted by the pituitary gland and are not formed by degradation of intact TSH in the peripheral circulation. I N T R O D U C T I O NTSH is known to consist of two dissimilar peptide chains, u and fi (Cornell & Pierce, 1973;Pierce et al., 1971). The exact biomolecular mechanisms involved in synthesis and union of these two chains have not been elucidated. The presence of separate subunits in the peripheral circulation, however, has been observed in hypothyroidism before and after TRH (Kourides et al., 1973; Benveniste et al., 1973), but subunit measurement in normal humans after TRH have not yet been reported. In addition, the question of how these subunits appear in the peripheral circulation has not yet been resolved. Two possibilities exist: (1) the a or fi chains may be directly secreted by the pituitary, (2) the intact hormone may be secreted and the subunits then formed by degradation of the intact hormone in the peripheral tissues. To resolve these possibilities, we have infused intact, purified human TSH to normal volunteers and compared the results to those obtained after stimulation of pituitary