To investigate the anterior pituitary function of human anovulatory cycles, hormonal environments were analyzed in an animal experimental model and women with anovulatory cycles. A specific antiserum to hypothalamic luteinizing hormonereleasing factor (LH-RF) was prepared in rabbits. Intravenous injection of 1.0ml of this antiserum to 4-day cycling female rats on the proestrous day blocked ovulation in the following cycles without changing regular estrous cycles on vaginal smear. Thus experimental anovulatory cycles were induced in antiLH-RF serum-treated rats. In this experimental model, LH surge on the proestrous evening was blocked but LH and FSH were maintained at the basal levels. In human anovulatory cycles, serum LH and FSH levels were also not significantly reduced except during the period of LH surge, and blood estradiol-17β levels were similar to the levels of women with normal ovulation. Serum progesterone levels were higher in the normal women after the expected day for ovulation. These data may indicate that the anterior pituitary is able to secrete its gonadotropins without stimulation by LH-RF and this tonic discharge of gonadotropins would maintain the basal levels of ovarian secretion of steroids.

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Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients.
It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion.

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Sensitive and specific radioimmunoassay for substance P was developed using synthetic substance P and ¹²⁵I-N^α-tyrosyl-substance P. Substance P-human α-globulin conjugate was used for production of anti-substance P antisera in rabbits. Synthetic substance P was used as a standard and the dextran-coated charcoal method was employed to separate the free peptide from that bound to antibodies. No crossreactions by physalaemin and eledoisin observed in this system proved its high specificity to substance P. N^x-Tyrosyl-substance P and [Tyr¹]-substance P showed the displacement curves indistinguishable from that of the standard substance P. Neither substance P5-11 nor substance P_6-11 competed with the tracer at the concentration used. The minimum measurable dose of substance P by the assay system was 2.5-5 pg/incubate.
Utilizing the system, human plasma samples from 42 healthy volunteers of both sexes were shown to contain immunoreactive substance P in amounts that averaged 298pg/ml in male and 251pg/ml in female. Substance P-like immunoreactivity was also demonstrated in hot-water extracts of porcine duodenum, jejunum, ileum, cecum, middle colon, rectum, pancreas, stomach and pituitary. The highest concentration (379 ng/g wet weight of organ) was found in the pituitary, and the ileum (7.9ng/g wet weight of organ) and jejunum (1.9ng/g wet weight of organ) were rich in the contents.

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A radioimmunoassay for human plasma corticosterone has been developed. Antiserum against corticosterone was produced in rabbits immunized with corticosterone 21-hemisuccinate conjugated to bovine serum albumin. The antiserum cross-reacted with progesterone, DOC and dehydrocorticosterone more than 20%. After the extraction with ether, and the separation by Sephadex LH-20 microcolumn chromatography, recovery was 51.2±12.1% in 50 assays. The mean coefficient of variation between assays was 7.7% and within assays was 8.6%. Human plasma corticosterone is measured readily by assaying aliquots of an ether extract of 0.05 to 0.1ml of plasma after microcolumn chromatography. The mean plasma corticosterone concentration at 9a.m. was 7.1±3.2ng/ml in 45 normal subjects. Plasma corticosterone increased 5.2 times as much as basal values after ACTH injection, whereas radioimmunoassayed cortisol increased 2.4 times. On the other hand, plasma corticosterone decreased to 22.6% of basal values at four hours after 1 mg dexamethasone, whereas radioimmunoassayed cortisol decreased to 12.3% of basal values.

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A case of partial lipodystrophy developing anterior pituitary insufficiency, chronic glomerulonephritis and pulmonary fibrosis was reported. The patient died of respiratory failure secondary to pituitary crisis during the hospital course.
From the clinical course in recent several years and the postmortem examination the head injury following car accident in the past history was considered to be the most plausible cause of hypopituitarism. The etiology of pulmonary fibrosis remained unresolved.

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Diagnosis of Cushing's disease in most cases can be established by the standard dexamethasone suppression test without difficulty. However, some cases were known to be normally suppressed by the standard low dose of dexamethasone (2mg daily). The case we encountered recently was also normally suppressed by either the rapid (Nugent) or the standard (Liddle) method. This fact prompted us to study the usefulness of a single dose of 0.5mg of dexamethasone to suppress the plasma cortisol in the normal.
It was concluded that the single oral dose of 0.5mg of dexamethasone given at 11 p.m. on the previous night suppressed the plasma cortisol efficiently the following morning in the normal, thus making the differentiation of particular cases of Cushing's disease from the normal possible. The disappearance of plasma dexamethasone did not differ significantly between the normal and the Cushing's disease.

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Intravenous injections of varying doses of 5-HTP (1, 3 and 5mg/100g body wt), a precursor of serotonin, caused a significant and dose-related increase in plasma prolactin concentrations in urethane-anesthetized rats. Increases in plasma prolactin concentrations caused by 5-HTP (1mg/100g body wt iv) were abolished by the concomitant administration of L-DOPA (2mg/100g body wt iv). Plasma prolactin levels were also significantly elevated following the injection of 5-HTP in rats with complete hypothalamic deafferentation, whereas 5-HTP had no significant effect on plasma prolactin levels in rats with extensive hypothalamic ablation. These results suggest that 5-HTP causes prolactin secretion by stimulating the serotoninergic mechanism in the hypothalamus.

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Alloxan diabetic rats with fasting blood glucose levels above 300mg/100ml were treated with oral administration of water-in-oil-in-water (W/O/W) insulin emulsions at a dose of 50 U/100g body weight, three times daily for 10 to 14 days. The course of diabetes was followed by determinations of glucose levels in blood and urine.
During treatment with oral W/O/W insulin emulsions, daily excretion of urinary glucose decreased by about 30 to 40%(2 to 3g/day) in all of the five rats studied, and returned to the pre-treatment levels after the treatment being discontinued. During treatment, a significant reduction in fasting blood glucose levels was observed in 4 out of 5 rats, giving the decrease by 18 to 44%. Quantitative estimates suggested that the effectiveness of 50 U/100g of oral W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at a dose of 0.5 U/100g.
Although oral W/O/W insulin emulsions are still of low efficiency, these results would indicate that diabetes can be controlled by effective oral insulin preparations.

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The interaction between mouse choriomammotropin and mouse mammary glands was examined by radioreceptor assays using ovine prolactin (NIH-P-S9) iodinated by lactoperoxidase as a tracer. Mouse pituitary extracts and placental extracts were subjected to 10% acrylamide gel electrophoresis. Gels were cut into 2-mm segments after electrophoresis, and stored in 1ml 0.05M phosphate buffer (pH 7.4) containing 0.05M NaC1 overnight for elution. Lactating mammary tissues from D strain mice were incubated for 120 min in 1ml Medium 199 containing 6 ng of ¹²⁵I-prolactin and 0.1ml of each eluate. Pituitary extracts displaced ¹²⁵I-prolactin only at the position which coincides with the prolactin band. Displacement was observed at two positions of the gel when placental extracts were used. Relative mobilities (Rm) were 0.21 and 0.71, respectively. The slowly migrating component of choriomammotropin inhibited the binding of 125I-prolactin more strongly than the rapidly migrating one. Neither of them was identified as a distinct band in stained gels. The molecular weight of ovine prolactin, mouse pituitary prolactin and the slowly migrating component of mouse choriomammotropin was estimated to be 23000 using disc electrophoresis but the ion charges of these hormones were considerably different.

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Carcinoembryonic antigen (CEA) and calcitonin (CT) were simultaneously determined in sera and tumor tissues from 15 patients with medullary carcinoma of the thyroid (MCT). Serum CEA was increased in all but one patient, and CT did in all of them. Both levels were significantly related to the weight of excised tumor, but not to the presence of metastasis. Furthermore, a significant correlation was noted between the basal levels of CT and CEA. Both levels fell to normal after a radical operation had been performed. Tissue concentrations of CEA and CT in the MCT were more than 100 times those in hyperthyroidism, and the ratios of tissue over serum levels averaged 770 in CEA and 1000 in CT. In the calcium infusion test, CEA levels were not significantly changed in contrast with a distinct increase in CT levels. The results indicate that CEA and CT represent separate activities of the tumor cells, and that circulating CEA together with CT is a useful indicator in the diagnosis and follow-up of the disease.

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Properties of the four purified components of whale thyroid-stimulating hormone (TSH) have been compared. The amino acid composition shows close similarity among these components. Their hexosamine and sialic acid contents are of the same magnitude, whereas the neutral sugar composition differs somewhat from each other. The molecular weight of whale TSH determined by sedimentation equilibrium is 29, 000, and no difference in molecular weight as well as in Stokes radius as determined by gel filtration has been detected among these four components.
The amino acid and carbohydrate compositions of whale TSH resemble those of TSH from other species, especially those of non-primate mammalian TSH. Whale TSH contains, unlike bovine TSH but like human TSH, 1-2 residues of sialic acid as a constituent carbohydrate.

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Plasma hCT levels were less than 50pg/ml in 50 normal subjects. In 16 patients with medullary carcinoma of the thyroid (MCT), plasma hCT levels were distinctively elevated and they fell significantly after total thyroidectomy, but in 11 of them plasma levels were still high, indicating the presence of metastases. In 74 patients with the other types of malignancy, plasma hCT levels were found to be high in 9 cases (3 oat cell carcinoma of the lung, 4 malignant carcinoids, one malignant pheochromocytoma and one acute myelocytic leukemia). Except for the leukemic case, all these tumors were derived from neural crest. In 12 patients with primary hyperparathyroidism, plasma hCT levels were less than 20pg/ml. In 13 hypoparathyroid patients, two with pseudohypoparathyroidism and one with pseudoidiopathic hypoparathyroidism, plasma hCT levels were slightly elevated. Some patients with uremia had elevated plasma hCT levels, but there was no relation between plasma levels of hCT and those of PTH, urea nitrogen or creatinine. In response to Ca (4.5mg/kg/10 min) or tetragastrin (4μg/kg/5 min) infusion, a marked increase in plasma hCT was observed in all patients with MCT, but not in normal subjects. In 5 hypoparathyroid patients, a significant increase to both stimuli was also observed in all cases. Two patients with pseudopseudohypoparathyroidism responded to the Ca load.
These results indicate that the determination of plasma hCT levels especially after the short Ca or tetragastrin infusion is important to study various pathological conditions.

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On the 22nd day of gestation in rats, fetuses of acutely adrenalectomized mothers were injected subcutaneously with 0.43μCi 4-¹⁴C-progesterone in 0.05 ml saline. Ten and 20min after injection to fetuses, samples were taken to determine the ¹⁴C progesterone metabolites in the plasma and adrenal glands.
After extraction of the samples taken, the metabolites were separated by twodimensional thin-layer chromatography and identified by autoradiography. 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, corticosterone and 11β-hydroxyprogesterone were identified in the plasma of injected fetuses, and, in far smaller amounts, in the plasma of their mothers. The plasma of noninjected fetuses also contained very small amounts of these corticoids. The fetal adrenal glands contained far smaller amounts of radioactive steroids than the fetal plasma did.
The results obtained show that steroids of fetal origin can cross the placenta in and out, constituting evidence that the fetal adrenal glands are the only source of the plasma corticoids of their adrenalectomized mothers.

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The effects of either single injection or continuous infusion of synthetic Gn-RHon plasma hCG levels were studied in 5 pregnant women (14-38 week gestation). No definite increase of hCG level was seen in all the cases studied. In view of large dosages of Gn-RH used in this study in comparison with its minimum effective dose for the pituitary gonadotropin release, Gn-RH seems unlikely to play a role in hCG secretion during human pregnancy.

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Synthetic LHRH, at a dose of 5μg/kg, induced a marked increase in the serum LH level but a marked decrease in the serum prolactin level when injected iv to normal adult female rats on the day of estrus. In androgenized adult rats which had been showing persistent estrous vaginal smears, a less marked increase in the serum LH level was shown following injection of LHRH. Prolactin level decreased only slightly in these animals. Control level of serum prolactin in normal estrous and androgenized rats were 4.95±0.35 and 5.42±0.65mIU/ml, respectively.
Thyroidectomized-normal cycling rats responded to LHRH with a slight decrease in the serum prolactin level when injected on the day of diestrus. Prolactin level increased, however, 5min after LHRH injection in thyroidectomized-androgenized adult rats, which were thyroidectomized at the age 4, 6 or 10-12 weeks and have retained a low prolactin level similar to that in the diestrous stage of normal cycling rats thereafter.
The present results suggest that regulatory system of prolactin secretion became labile by androgenization and this status led to the release of prolactin by LHRH treatment after thyroidectomy.

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One male rat pituitary placed in a chamber was perifused with cyclic somatostatin (GIF) for 30 min. Either 160nM or 1.6μM GIF caused a decrease in the release of GH. The release of TSH was also decreased by 160nM GIF, and paradoxically increased by 1.6μM GIF. Increasing the dose of GIF to 16μM resulted in an abrupt rise in the release of both GH and TSH during the perfusion; then the level of GH decreased to the nadir level followed by an elevation above the base line, while that of TSH promptly fell back toward the base line. The release of PRL was not clearly affected by 16μM GIF.[Tyr⁸]-GIF did not have such stimulatory activities. These results indicate that GIF not only inhibits the release of GH and TSH, but also stimulates that of GH and TSH in this system, depending on its dose.

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