The influence of estrogen, progesterone and testosterone on the activities of alkaline and acid phosphatases, adenosine triphosphatase and succinate dehydrogenase were determined by cytochemical methods in sarcoma 180 and Ehrlich's carcinoma cells transplanted in male and female Swiss mice. The results revealed differential effects of the sex hormones on different enzymes which seemed to depend on the type of tumour cell studied and the sex of the host mice.

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The purpose of this study is to ascertain whether or not prostaglandin (PG) E₂induces LH release by modifying or modulating the release or action of neural transmitters.
PGE₂injected iv into spayed rats primed two days earlier with 10βg estradiol benzoate increased the plasma levels of LH 10 min later as measured by radio-immunoassay. The peak of plasma LH was not changed by prior treatment with βorα-adrenergic receptor blockers, propranolol or phenoxybenzamine. The peak level of plasma LH did not alter in rats treated with DL-α-methyl-p-tyrosine methyl ester HCI (α-MPT) or sodium diethyldithiocarbamate (DDC). Similarly, the peak of plasma LH was not changed by prior treatment with imipramine. Administration of PGE₂produced an increase in anlerior pituitary and plasma, but not hypothalamic cyclic AMP concomitantly with the elevation in plasma LH.
Although it is possible that the effect of PGE₂could be mediated by another transmitter system, as yet unknown, or that the effect of PGE₂on LH release could be mediated via the adenylate cyclase-cyclic AMP system, the results indicate that PGE₂does not act trans-synaptically, but probably acts directly on LH-RH neurons.

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A case of 20-year-old woman with hypogonadotropic hypogonadism and anosmia is reported, since very few female cases of Kallmann's syndrome have been reported so far in Japan. Three uncles on the father's side had no children. Height was 168cm, and arm span 165cm. The olfactory test revealed complete anosmia. Bone age was 13year. Chromosome was 46 XX and normal karyotype. Basal levels of serum FSH, LH and estrogens (E₁, ₂ and ₃) were low. Serum FSH and LH levels rose slightly only after LH-RH administration, and did not increase in clomiphene test. Plasma estrogens did not increase after daily injection of 150 IU of HMG for 3 successive days. The response of serum GH to arginine infusion was normal, while that to insulin-induced hypoglycemia was poor.

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The effects of intravenous carrier-free salmon calcitonin on renal clearances of phosphate, calcium, magnesium, sodium and potassium were studied in male parathyroidectomized (PTX) and intact rats. Both natural and synthetic hormone, when infused at constant rates (0.005-0.5 MRC U/hr), produced a rapid increase (peaking at about 60-90min) in phosphate clearance. However, the maximal increase was transient in nature in PTX rats. In intact rats, the phosphaturic response was somewhat more pronounced and the decline after the peak was rather modest. When a large amount (4 MRC U) of calcitonin was given in divided doses, the second dose produced a lesser extent of phosphaturia in both intact and PTX rats.
The phosphaturic response was accompanied by an increase in sodium and potassium clearances in PTX rats and by an increase in potassium clearance in intact rats. A fall in the apparent clearance values for calcium and magnesium occurred and was maintained throughout the infusion period of hormone in both intact and PTX rats
In conclusion, PTX rats respond to the intravenous administration of salmon calcitonin with a transient phosphaturic response which is accompanied by parallel diuresis of sodium and potassium along with sustained retention of calcium and magnesium by the kidney.

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The dissociation of thyroid 27 S iodoprotein by sodium dodecyl sulfate (SDS) and by succinic anhydride was investigated by means of ultracentrifugation and polyacrylamide gel electrophoresis. The iodoprotein obtained from either a human or hog was dissociated into three kinds of subunits (S-19, S-17 and S-12) by SDS treatment. At increased concentrations of SDS, the S-12 subunit was predominant among the dissociation products. The succinylation of 27 S iodoprotein showed essentially the same dissociation pattern as in the case of SDS treatment.
The dissociation products of the protein preparations of different animals were qualitatively the same as those of thyroglobulin of the respective animals, confirming the hypothesis that 27 S iodoprotein was composed of two molecules of thyroglobulin. However, the extent of dissociation of 27 S iodoprotein measured by S-12 formation showed higher resistancy of the protein to the dissociating agents than that of thyroglobulin.
The contents of sialic acid and hexose as well as iodoamino acids of 27 S iodoprotein were found to be the same as, or not far from, those of thyroglobulin.
The dissociability and chemical composition of 27 S iodoprotein was discussed with reference to the subunit structure of the protein.

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The response in serum thyrotropin (TSH) to synthetic thyrotropin-releasing hormone (TRH) as well as serum free thyroxine index (FT₄I) and free triiodothyronine index (FT₃I) was investigated in six patients with familial thyroxine-binding-globulin (TBG) deficiency. The total serum thyroxine (T₄) and triiodothyronine (T₃) concentrations were significantly decreased, compared with those of normal subjects (3.4±0.9 μg/dl, mean±S. D. vs. 9.0±1.5 μg/dl, p<0.01 and 87±27 ng/dl vs. 153±37 ng/dl, p<0.01, respectively). FT₄I was lower than the normal range in all but one (5.3±1.5 vs. 8.9±1.6, p<0.01), whereas FT₃I was all in the normal range and of no significant difference from the normal control (132±22 vs. 148±25). Serum TSH concentrations in TBG deficiency were all in the normal range (1.0-4.2 μU/m/) and the maximum TSH increments following TRH 500 μg iv were 8.9±2.0 μU/ml and of no significant difference from the normal control (10.2±4.5 μU/ml). These results indicate that the euthyroid state in familial TBG deficiency is more clearly defined by TRH-test and the normal response to TRH in familial TBG deficiency is presumably under the control of the serum free T₃ level rather than the serum free T₄ level.

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The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H₂-receptor antagonist, but not by chlorpheniramine, a histamine H₁-receptor antagonist. The effect of norepinephrine was completely inhibited by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine-or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E₂. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E₂ and could play an important role in thyroid physiology.

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Female mice of the C57 Black/Tw strain were injected daily with 100μg testosterone, 50μg testosterone propionate (TP), 100μg 5α-dihydrotestosterone (DHT) or 50μg 5α-dihydrotestosterone propionate (DHTP), for 10 days from the day of birth. Two other groups of female mice were given neonatal injections with 20μg estradiol-17β and 100μgg progesterone for 10 days, respectively. All mice were ovariectomized at 60 days of age and killed at 90 days. In 100% of neonatally estrogenized or androgenized, ovariectomized mice, the cranial part of the vagina was lined with stratified epithelium with either cornification or parakeratosis or mucification. Stratification only or stratification with superficial squamous metaplasia or cornification took place in the uterine epithelia of 18% of the TP-treated, 75% of the DHT-treated and 50% of the DHTP-treated, ovariectomized mice. In contrast, neonatally estrogenized, ovariectomized mice did not show the estrogen-independent, persistent uterine changes. Neonatal progesterone treatment failed to induce the permanent changes in the vaginal and uterine epithelia.

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Female mice of the C57 Black/Tw strain given 5 daily injections with 100 μg testosterone (T) or 5α-dihydrotestosterone (DHT) from the day of birth showed estrogenindependent persistent proliferation and cornification of the vaginal epithelium in adulthood. The vaginal epithelium of the mice was essentially similar to that of the controls in histological structure during or shortly after neonatal injections of the androgens. In T-and DHT-mice aged over 20 days, however, a marked proliferation with or without superficial cornification took place in the epithelium lining the proximal and middle parts of the vagina (Müllerian vagina), while neither proliferation nor cornification occurred in the epithelium of the distal vagina (urogenital sinus vagina). On the second day of postnatal life in mice given a single injection with T on the day of birth, the mitotic activity in the epithelium of the middle vagina was heightened, but it dropped to the control level on the third day and remained low until 20 days. By contrast, the mitotic rates in the epithelium of the rest of the vagina in T-mice and of all parts of the vagina in DHT-mice were approximately the same as in the controls until 20 or 30 days. The mitotic rates in the epithelium of the Müllerian vagina were markedly elevated in T-mice at 20 days of age and DHT-mice at 30 days, and thereafter remained almost unchanged until 60 days of age. These results were different from the findings in mice given neonatal injections with the dose of estradiol-17β(E) capable of estrogen-independent vaginal cornification (Iguchi et al., 1976). The present findings seem to indicate that the mechanism involved in the induction of estrogen-independent vaginal changes by neonatal administration of androgen (T, DHT) is different from that following neonatal treatment with estrogen (E), although androgen and estrogen act directly on the vaginal epithelium of neonates.

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Adult mice which had received 10 daily injections of 20μg estradiol beginning with the day of birth were in a “persistent-estrous” state, showing ovary-independent proliferation and cornification of the vaginal epithelium. Ultrastructural changes of the vaginal epithelium in neonatally estrogenized mice was examined after a single postpuberal injection of 10μg estradiol and compared with those seen in normal mice to estrogen. In ovariectomized normal mice, the basal cells were round. The nucleus was polygonal and contained peripheral condensed chromatin. After estradiol treatment, the basal cells became columnar. The nucleus was round to oval, containing dispersed chromatin. In neonatally estrogenized ovariectomized mice, the basal layer of vaginal epithelium consisted of round cells with polygonal nuclei, much as in normal ovariectomized mice. The nucleus occupied a large area of the cytoplasm and contained prominent nucleoli. Intercellular spaces were moderately distended. Late estradiol treatment resulted in distended intercellular spaces and in the appearance of the other cell type along with round cells in the basal layers: columnar cells containing an oval nucleus with dispersed chromatin, resembled the basal cells in normal ovariectomized mice receiving postpuberal estrogen injection. The intercellular spaces between the columnar cells were narrow compared with those between round cells. However, the nuclei of round cells still had prominent nucleoli and peripheral condensed chromatin regardless of subsequent estrogen treatment. This fact suggests that these nuclei do not respond to estrogen. These results clearly show that the vaginal epithelium of neonatally estrogenized mice with ovary-independent persistent cornification consists of a mixed population of cells.

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In order to compare the acute effects of three kinds of antithyroid agents of iodide (I^-), propylthiouracil (PTU) and PTU combined with iodide (PTU+I^-) on thyroid function in hyperthyroid patients with diffuse goiter, serum concentrations of thyroxine (T₄), triiodothyronine (T₃), T₃-resin sponge uptake (T₃-RU) and free thyroxine index (FT₄I) were employed as thyroid function parameters. In the group given iodine (1mg/day) as iodinated-lecithine, the initial values of T₄, T₃, T₃-RU and FT₄I were 20.9±1.6μg/100ml (T₄), >740 ng/100ml (T₃), 49.5±2.3%(T₃-RU) and 14.7±1.8 (FTA₄I). At the end of one week of theranv, they decreased clearly to 15.6±2.2 μg/100ml, 457±87ng/100ml, 42.2±4.0% and 9.7±2.4. Theso-called “escapephenomenon” from iodide inhibition was observed in serum T₄, T₃-Ru ana FT₄I values at the end of two weeks of iodide therapy, while serum T₃ continued to decrease but the value of T₃ was far outside of the normal range. In the PTU group (300 mg/day), thyroid function parameters were 22.5±0.8μg/100 ml (T4), >592ng/100ml (T₃), 54.9±1.0%(T₃-RU) and 18.7±1.0 (FT₄I) before treatment. Theydecreased continually week by week. At the end of four-week treatment with PTU, the value of eacn thyroid function parameter was 11.1±1.9 μg/100ml, 229±56 ng/100ml, 36.6±4.4% and 5.7±1.7. In the group of hyperthyroidism simultaneously given both PTU and iodide (300mg/PTU and mg/iodine), these thyroid function parameters decreased as well as in the group treated with PTU alone for more than two weeks. More rapid or significant decrease of T₄, T₃, T₃-RU and FT₄I in PTU+I^- group than in PTU group was observed in the present study.
These results suggested strongly that iodide alone was not an adequate therapy for hyperthyroidism as well known and they were also compatible with the idea that the concomitant administration of PTU and iodide was more effective in the early phase of therapy of hyperthyroidism than PTU alone.

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Treatment with concanavalin A at 100μg/ml or higher concentrations significantly increased ¹⁴C-1-glucose oxidation in dog thyroid slices as reported in other tissues. This treatment exerted no effect on tissue cyclic AMP levels.
Neuraminidase at the same concentrations also had similar effects on these parameters.
Neither concanavalin A nor neuraminidase at the concentrations up to 100μg/ml had the TSH effect on both tissue cyclic AMP and ¹⁴C-1-glucose oxidation.
These results indicate that modification of carbohydrate moieties of glycoproteins on the cell surface may cause an increase in glucose metabolism without any critical effect on cyclic AMP system and in the process of TSH response.

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A simple and sensitive radioimmunoassay for 11-deoxycortisol was developped. The antiserum produced in rabbits by immunizing with a complex of 11-deoxycortisol-3-oxime and bovine serum albumin (BSA) has little cross-reactivity with other endogenous steroids. The immunoassay procedure requires only one-step ethanol denaturation of binding proteins in plasma and extraction by an organic solvent can be omitted. Furthermore, use of ¹²⁵I-labeled tracer significantly simplify the counting procedure. The method is sensitive enough to detect 1μg/100ml of 11-deoxycortisol.
Plasma 11-deoxycortisol levels measured by this method after the administration of a single dose of metyrapone ranged from 5.0 to 19.2μg/100ml, whereas they were 0 to 4.0μg/100ml in hypopituitary patients.
It is concluded that this simple method is useful for the routine assay of plasma 11-deoxycortisol as a parameter of the metyrapone tests.

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