Globulin preparations from the sera of 104 untreated patients with Grave's disease have been tested for their thyroid-stimulating antibody (TSAb) activities. Eighty-one of the samples (78%) were positive in the assay for the thyrotrophin-binding inhibitory immunoglobulins, 48 samples (46%) contained human thyroid adenyl cyclase stimulators (HTACS) and 71 (68%) contained human thyroid stimulators (HTS) measured as stimulation of colloid droplet formation in human thyroid slices. All 104 samples were positive in one or other of the assays, 29 (28%) were positive in all three assays and 38 (37%) in two. All samples were tested for their specific TSH-binding characteristics, 40 (38%) possessed 'B-type' binding sites (previously characterized as TSH-binding sites with low affinity but high capacity for the ligand) but the remaining 64 samples (62%) were no different from normal control samples and had 'A-type' binding sites (high affinity but low capacity binding sites for TSH). Samples without detectable thyrotrophin-binding inhibitory immunoglobulin did not contain B-type TSH-binding globulins. Globulins exhibiting B-type binding were more active in the HTACS and HTS assays. The B-type TSH-binding globulins have a characteristic, dose-dependent reducing effect on the human thyroid adenyl cyclase stimulation by TSH whereas A-type globulins do not. Globulins exhibiting B-type TSH-binding may therefore have a significant effect on assays for TSAb activities. The method used to measure TSAb have been reviewed from this point of view.
Globulin preparations (41) from patients with Graves's disease (positive to thyroid stimulating immunoglobulins; TSI) and 12 from healthy persons (TSI-negative) were tested for their specific thyrotrophin (TSH)-binding properties. Globulins from both groups possessed binding sites for 131I-labelled TSH. The mean dissociation constant (Kd) was 6.8 pmol/1 per mg globulin and the maximum specific binding (Bmax) was 3.0 pmol/mg globulin per 1 for the TSI-negative control group. Twenty-four (58.5%) globulin preparations from the TSI-positive group had similar TSH-binding characteristics with mean Kd of 7.2 pmol/1 per mg globulin and Bmax of 3.6 pmol/mg globulin per 1 (A-type binding) but the remaining 17 (41.5%) bound TSH in a different fashion with Kd of 71.5 pmol/1 per mg globulin and Bmax of 13.6 pmol/mg globulin per 1 (B-type binding). Both types of specific TSH binding reached the maximal level within 1 h of incubation and had an optimum pH of 7--8. There was a linear correlation between the amount of bound TSH and the globulin content of the samples. Both types of binding were reversible by the addition of an excess of TSH and gonadotrophins, ACTH, prolactin and insulin competed with TSH for the binding sites only when in relatively high concentrations. The binding sites were associated with macromolecules; they emerged with the void volume after chromatography on Sephadex G-200 and migrated with immunoglobulin G (IgG) on paper electrophoresis. The binding capacity of the globulin preparations could be decreased by preincubation with antiserum to human IgG or with human thyroid membranes.
Plasma concentrations of FSH and LH were measured in ovariectomized, ovohysterectomized, hysterectomized and sham-operated adult, non-pregnant rats at 3, 14, 21 and 28 days after operation. From day 21 after the operation onwards, there were higher concentrations of FSH in plasma in ovohysterectomized than in ovariectomized animals. The concentration of LH was not influenced by hysterectomy. The inhibitory response of FSH and LH to a single dose of oestradiol was not altered by any of the operations. By 2 weeks after surgery, pituitary FSH content had increased in ovohysterectomized animals compared with ovariectomized ones, but this difference was eliminated when ovohysterectomized animals were treated with crude uterine extract. Pituitary contents of LH and prolactin were not influenced by hysterectomy or by treatment with uterine extract, thus indicating the specificity of an inhibitory effect of the uterus on FSH levels. Treatment of hysterectomized and intact animals with uterine extract resulted in a reduction in the weight of the ovaries of 23-38% (P less than 0.05), indirectly showing the presence of an FSH-inhibiting substance in the extract. Fractionated uterine extract inhibited FSH synthesis by rat pituitary cells in vitro, but had no effect on LH synthesis. Chromatographic analysis indicated that the FSH-inhibiting substance in the uterus has a molecular weight of 10,000-20,000.
The electrolytic lesion of locus coeruleus reduced the hypothalamic noradrenaline (NE) content to 28 % of the control values and resulted in a marked decrease of the plasma FSH level in ovariectomized rats before puberty. The local microinjection of 6-OH-dopamine into the locus coeruleus led to a reduction in the hypothalamic NE content to 21 % of the control level and induced a decrease of the compensatory ovarian hypertrophy and that of the plasma FSH level. The electrolytic lesion of the locus coeruleus or the 6-OH-dopamine treatment failed to influence the plasma growth hormone (GH) level. The observations support the hypothesis that ventral noradrenergic projection is involved in controlling the pituitary FSH secretion.There is histofluorescent evidence that the hypothalamus contains NE projec¬ tion of the ventral ascending adrenergic pathway, which innervates the neurosecretory elements of the basal-medial hypothalamus (Fuxe et al. 1968;Ungerstedt 1971). The injection of 6-OH-dopamine results in selective degeneration of central catecholaminergic pathways (Ungerstedt 1971). Thus, the anterolateral injection of 6-OH-dopamine in the hypothalamus produces a significant reduction in the NE content (Sechzer et al. 1973).Other observations support the hypothesis that NE fibers are involved in the hypothalamic mechanism activating the pituitary gonadotrophin release
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