An alternative pathway of Trp metabolism involves the conversion of Trp to kynurenine by indoleamine-2,3-dioxygenase, which leads to synthesis of the neurotoxin, quinolinic acid. This study explores the relationship of indoleamine-2,3-dioxygenase activity with stages of HIV infection. Sera from 206 HIV-positive and 72 seronegative subjects were analyzed for Trp and kynurenine. The kynurenine-to-Trp (KT) ratio was calculated. The mean KT ratio of seronegative controls was 36.6 ± 10.9, and the median ratio was 34.9. The upper limit of the seronegative KT ratio, defined as mean + 2 SD, was 58.4. Patients with HIV infection showed a reciprocal relationship between the KT ratio, the CD4 count, and the stage of the disease. The median KT ratios for asymptomatic and AIDS patients were 50.5 and 117.0, respectively. This study shows that the serum Trp concentration is markedly decreased and that the kynurenine concentration is increased with immune stimulation in HIV infection. This may lead to changes in quinolinic acid and explain some of the pathogenesis of AIDS dementia.
Fourteen patients with a typical history of Sheehan's syndrome underwent pituitary function tests with simultaneous injections of 100 micrograms LH-RH, 200 micrograms TRH and 0.05--0.1 units of soluble insulin per kg body weight. Serum prolactin levels remained unchanged in all of eleven subjects given TRH. GH levels did not rise after hypoglycaemia in five subjects. In contrast serum LH and FSH rose significantly in twelve out of fourteen subjects given LHRH and serum TSH rose significantly in five out of seven subjects given TRH. It is concluded that pituitary function is relatively preserved for LH and FSH but not for prolactin and GH in Sheehan's syndrome. It is further suggested that absence of a rise in prolactin following TRH stimulation may provide the most sensitive test of pituitary hypofunction in postpartum haemorrhage.
Anterior pituitary glands from male rats aged 21, 40, 60 or 95 days were incubated in medium containing 0, 2 or 20 ng luteinizing hormone-releasing hormone (LH-RH)/ml. Incubates were assayed for LH by radioimmunoassay (RIA), by the radioligand-receptor assay (RLA) using testicular homogenates as the source of receptor and, in some instances, by the ovarian ascorbic acid depletion assay (OAAD). Irrespective of the dose of added LH-RH, glands from rats aged 40 and 60 days always showed a higher release of LH, as determined by RLA, than glands from animals aged 21 or 95 days. Measurement by RIA showed a similar pattern to RLA in the basal release of LH, but in the presence of LH-RH showed little difference in LH release by glands from rats aged 40, 60 or 95 days. The LH release caused by the higher concentration of LH-RH was always greater when measured by RLA than by RIA. Assay of comparable incubates by OAAD showed close agreement with RLA estimates in four incubations (mean index of discrimination 1.07; range 0.86-1.18) and consistent disagreement with RIA estimates (1.64; range 1.38-1.99). In contrast to the results with incubates, homogenates of pituitary glands from male rats of various ages showed close agreement of estimates by RLA, RIA and OAAD. These results suggest that RIA underestimates the LH-RH-stimulated release of LH in vitro from the male rat pituitary during some stages of sexual maturation.
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