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Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.

With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

The effect of thyroid hormones on TSH synthesis and release from the anterior pituitary of the rat, at the various stages of hypothyroidism was studied by injecting L-Triiodothyronine (T3) iv (1.5 microgram/100 g b.w.) to rats 5 days and 3 months post thyroidectomy (Tx-5d and Tx-3m rats). The changes in plasma and pituitary TSH levels, as well as in the metabolic clearance rate (MCR) of the TSH were followed for 3 days after the T3 injection. From these data TSH synthesis and release rates were determined. TSH release was inhibited in both experimental groups between 3 and 24 h after the injection. TSH synthesis was suppressed in the Tx-5d group to 35% of the initial value. However in the Tx-3m group it was stimulated to approximately 270%, 24 h after the T3. The data suggest that thyroid hormones may affect the synthesis of TSH in two opposite pathways, the first through the stimulation of protein synthesis and the second, inhibitory, as part of the feedback mechanism. Under short-term hypothyroidism, when protein synthesis is not yet diminished, the administration of thyroid hormones results in the inhibition of both TSH synthesis and release through the feedback regulation. In prolonged hypothyroidism, however, when protein synthesis is depressed, the effect of thyroid hormones on the stimulation of TSH synthesis predominates.

Highly specific anti-TSH antibodies were purified from a crude antiserum preparation by affinity chromatography using TSH-sepharose column as the adsorbant. This procedure completely eliminated the original LH binding activities. The purified anti-TSH antibodies were then coupled to CNBr activated sepharose 4 B and used in separating TSH from rat pituitaries by batch procedure. This method is demonstrated to be highly specific for purifying labelled TSH from pituitaries previously incubated in the presence of [14C]tyrosine. The effect of TRH on TSH biosynthesis is presented as a biological application of this procedure.

The time and dose dependent effects of T3 on the anterior pituitary (AP) TSH release and synthesis were studied in rats 5 days after thyroidectomy (T-5d). T3, in various doses, was injected iv to animals which were kileed at various times later. Plasma and AP TSH were measured. T3 lowered plasma TSH to a minimum within 3 h. An inverse linear relationship was found between T3, up to 634 +/- 134 ng/100 g b.w. (mean +/- SD) and plasma TSH. Higher doses of T3 did not lower plasma TSH any further. At T3 of 634 +/- 134 ng/100 g b.w. the specific AP binder was calculated to be 68% to 90% saturated; thus suggesting a relationship between occupancy by T3 of the AP binder and the regulation of TSH release. The TSH release and synthesis rates were compared after 0.5 micrograms, 1 microgram and 25 micrograms T3. All three doses of T3 suppressed the release as well as the synthesis. The effect of T3 on the synthesis rate, however, lagged behind the effect on the release both in time and magnitude.

A sensitive and specific radioimmunoassay has been developed for rat prolactin (rPRL), employing the double antibody solid phase technique for the separation of free and antibody-bound [125I]rPRL. The anti-serum was raised in rabbits and showed no cross-reaction with rat growth hormone (rGH), follicle stimulating hormone (rFSH), luteinizing hormone (rLH) and thyrotrophin (rTSH). The immunosorbent (sheep anti-rabbit IgG bound to cellulose) showed a surprisingly high binding of [125I]rPRL, but not of the other iodinated anterior pituitary hormones. Addition of serum to the incubation mixtures prevented the binding between [125I]rPRL and the immunosorbent. Three different clonal strains of pituitary cells have been examined for production of rPRL, rLH and rTSH, both in the basal state as well as after treatment with thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone (LH/FSH-RH). Monolayer cultures of two of the cell strains produced and secreted rPRL spontaneously, and they showed a 2-fold increase in rPRL production after treatment with TRH (3-10(-7) mol/1). The third cell strain did not produce rPRL spontaneously, or after treatment with TRH. None of these cell strains could be stimulated to produce rTSH by treatment with TRH. Treatment of the same three cell strains with LH/FSH-RH (1.2-10(-6) mol/1) failed to induce production of rLH, and there were no changes in production of rPRL. Prostaglandins E1 and E2 (3-10(-8) mol/1) and oestradiol-17beta (10(-7)-10(-10) mol/1), however, stimulated the production of rPRL. The effects of TRH and prostaglandins E1 and E2 were observed within 24 h of treatment, while the first effect of oestradiol-17beta was seen after 3 days. These results suggest that the stimulatory effect of oestradiol-17beta on rPRL production differs from that of TRH and prostaglandins.