The prostate is one of the target organs of androgen. This fact is the foundation of the anti-androgen therapy for the treatment of prostatic of cancer as there are many prostatic cancers which show no response to hormone therapy. Since androgen acts via an androgen-androgen receptor complex in cytosol, trials to predict the effectiveness of the anti-androgen therapy for the treatment of prostatic cancers by means of the measurement of androgen receptor (AR) have been done. However some investigators emphasize that the response to hormone therapy and the contents of AR are not necessarily parallel. This discrepancy is probably due to the inaccurate measurement of AR. AR is measured by a radioreceptor-assay method, but it is possible that androgen binding proteins other than AR are also measured by the radioreceptor-assay method. In the human prostatic tissues, there are several androgen binding proteins other than AR. These are mainly testosterone-binding globulin (TeBG) and progesterone-binding protein (PBP). In this study, I attempted to separate and characterize androgen-binding proteins in human prostates.
500g of benign prostatic hyperplasia (BPH) tissues obtained from patients undergoing retropublic or suprapubic prostatectomy were used. In order to separate these androgen-binding proteins, DEAE-cellulose ion exchange chromatography was used. Prostatic cytosol was applied on the DEAE-cellulose column. Two ³H-R1881 binding peaks were eluted : one was a flow-through fraction (peak I), and the other was an 0.1M KCl eluted fraction (peak II). When human serum was applied to the column, one ³H-DHT binding peak flowed through the column (peak III). It was thought that peak III contained TeBG. In order to ascertain whether AR was composed in peak I or peak II, an inhibition test by various nonradioactive steroids, R1881, DHT, testosterone, progesterone and estradiol was performed. ³H-R1881 binding of peak I was not inhibited by DHT or testosterone, while ³H-R1881 binding of peak II was inhibited by DHT and testosterone. The androgen-binding affinity of the peak I and peak II fraction was also measured using Scatchard's analysis. The dissociation constant of peak I was 6.25nM, and that of peak II was 0.76nM. Judging from these measurements the androgen-binding protein of peak II contained a specificity and high affinity to androgen. Consequently it was thought that AR was composed in peak II. Peak II fraction was applied on a Sephadex G200 gel chromatography column. A single androgen binding peak eluted in the void fraction.
AR was purified by sequential chromatograpy on DEAE-cellulose, testosterone Sepharose and Blue Sepharose CL-6B. Purified AR maintained its androgen-binding capacity, and purification was 128 fold and recovery was 0.234%.

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Clinical usefulness of a radioimmunoassay of plasma arginine vasopressin concentration (AVP) during hypertonic saline infusion for the assessment of posterior pituitary function was studied in comparison with the conventional water deprivation test.
Infusion of 5% saline at a rate of 0.05ml/kg/min for 120min in 15 normal subjects induced an elevation of plasma osmolality (Posm) from 290.3±0.7 to 307.5± 2.1mOsm/kg with a resultant increase in AVP from 2.4±0.4 to 9.9± 2.2pg/ml. During the infusion, a highly significant correlation between AVP and Posm was observed with a regression line expressed as AVP = 0.40 (Posm - 283.0). In 22 polyuric patients, on the other hand, the infusion induced a marked elevation of Posm from 302.6±2.5 to 321.3±2.9mOsm/kg, but caused a slight (<5.8pg/ml) or no increase in AVP from the basal levels (0.5±0.1pg/ml).
A conventional water deprivation test was carried out in ten patients with neurogenic diabetes insipidus, including one who had coincidental nephrogenic diabetes insipidus. As would be expected, urine osmolality (Uosm) did not rise beyond Posm in seven of them. However, two of three other patients, who had a complete lack of AVP response to the hypertonic saline, were able to concentrate their urine with a maximal Uosm/Posm of 1.3 and 1.1 respectively.
The concurrent decrease in creatinine clearance to 49 and 57% of the initial values, respectively, indicated that a marked reduction in glomerular filtration rate due to severe dehydration was responsible for the unexpected concentration of urine in the patients with totally impaired AVP secretion.
Based on these results, we conclude that the direct measurement of AVP during hypertonic saline infusion is an essential procedure for the accurate evaluation of posterior pituitary function.

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By using the pre-ejection period (PEP), the left ventricular ejection time (LVET) and LVET/PEP ratio, cardiac function was investigated in 35 patients with Graves' disease (mild and severe), 13 patients with primary hypothyroidism and 35 normal subjects. The effect of treatment with antithyroid drugs, T₄ or Co-Q₁₀ was also evaluated.
Before treatment, PEP was significantly shorter and the LVET/PEP ratio was greater in mild thyrotoxic patients than in the control subjects. PEP and LVET/PEP ratio returned to control levels after the euthyroid state was maintained with antithyroid drugs. In severe thyrotoxic patients, PEP and LVET/PEP ratio did not show any significant change compared with the control subjects, although LVET was significantly shorter. In hypothyroid patients, marked prolongation of PEP, shortening of LVET and decrease in LVET/PEP ratio were shown and returned to control levels after the euthyroid state was maintained with T₄. PEP correlated curvilinearly with serum T₃ and T₄ concentrations. However, LVET/PEP ratio increased linearly from hypothyroid to mild thyrotoxic patients and decreased gradually in severe thyrotoxic patients. The inverse correlations between serum Co-Q₁₀ and T₃ and T₄ concentrations were shown in patients suffering from hypothyroidism to mild thyrotoxicosis. After the administration of 120mg Co-Q₁₀ for 7 days in mild untreated thyrotoxic patients, a significant shortening of PEP and an increase in LVET/PEP ratio and stroke volume were shown.
These data indicate that cardiac function in terms of PEP and LVET/PEP ratio is markedly influenced by serum thyroid hormone concentrations and Co-Q₁₀, modulates it.

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We investigated the mechanism of glucose intolerance in 51 patients with Cushing's syndrome. In an oral 100g glucose tolerance test, although prevalence of decreased glucose tolerance was very high as revealed in 36 of 47 patients (77%) studied, impairment was rather mild in the majority of patients and only 10 patients (21%) were judged as diabetic. Plasma insulin was measured in 12 patients and the mean values of these patients reached above normal levels after oral glucose load. When insulin secreting capacity was assessed by measuring the ratio of the incremental area of insulin above fasting level to the corresponding area of glucose during the test, Cushing's syndrome as a whole exhibited a normal ratio compared to 9 control subjects (113±115 vs. 144±78μU/mg, M±SD, ns), but in 3 patients with severe impairment of glucose tolerance reaching the diabetic range, the ratio was lower than normal (27±20 vs. 144±78μU/mg, M±SD, p<0.05).
The hypoglycemic effect of iv insulin was studied in 23 patients and was demonstrated to have decreased. Thus, we confirmed the presence of decreased insulin sensitivity, i.e. insulin resistance in Cushing's syndrome.
The age of patients showed positive correlation with the degree of impairment in glucose tolerance and insulin secreting capacity, but not with that of insulin sensitivity, that is, in patients with advanced age, glucose intolerance appeared to be severe with decreased insulin secreting capacity.
¹²⁵I-insulin binding to red blood cells in 8 patients was examined to elucidate the mechanism of insulin resistance in Cushing's syndrome. Percent specific binding at tracer concentration of insulin in Cushing's syndrome was not different from the value obtained in 19 normal subjects (8.2±3.0 vs. 7.7±1.0%, M±SD, ns). Receptor concentration and affinity were also normal.
From these observations, it is likely that glucose intolerance in Cushing's syndrome is primarily due to the effects of chronic glucocorticoid excess on tissue metabolism of glucose as characterized by the presence of insulin resistance, which is not due to a defect in insulin-receptor binding but rather caused by the alteration in post-receptor mechanism, and increased secretion of insulin can be considered as a compensatory mechanism. In some patients, however, a decrease in insulin secreting capacity, the cause of which is not clear but at least related to the patient's age, is found and seems to lead to severe glucose intolerance.

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The presence of cytosol estrogen receptor (ER) and the ER of nuclear extracts in normal uterine endometrium and endometrial adenocarcinoma tissues were determined by radioreceptor assay (RRA) and enzyme immunoassay (EIA). In addition the intracellular localization of ER and tissue distribution of ER positive cells was demonstrated by immunocytochemical assay (ICA).
(1) The levels of cytosol ER measured by EIA and RRA had a significant correlation in normal endometrium (r=0.90) (P<0.01) and endometrial adenocarcinoma (r=0.96) (P<0.01) as well as in breast cancer (r=0.93) (P<0.01).
(2) The ER measured by immunocytochemical method using the monoclonal anti-ER antibody obtained from breast cancer cells was applicable to the detection of the ER in uterine endometrial tissues.
(3) In endometrial adenocarcinoma, the levels of cytosol ER in G₁ (Highly differentiated adenomatous carcinoma) tissues (187.6±189.0 fmoles/mg protein) were significantly higher than those in G₂ (Moderately differentiated adenomatous carcinoma with partly solid areas) tissues (15.0±31.9 fmoles/mg protein) (P<0.05).
(4) The levels of cytosol ER peaked in the late follicular phase (432.0 fmoles/mg protein) and remained low in the other phases.
(5) Epithelial cells in the normal endometrium were stained uniformly by ICA, in contrast, ICA stained and nonstained cells existed concurrently in the same endometrial adenocarcinoma tissues. A similar finding was also shown in breast cancer tissues and may be related to the efficacy of anti-estrogenic drugs on the growth of whole cancer tissues.

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The changes in serum prolactin levels during the menstrual cycle have not been clarified yet. The present study was conducted to investigate whether the changes in serum prolactin levels during the menstrual cycle exist in ovulatory infertile patients having high prolactin release due to TRH administration described below (transient hyperprolactinemia) and control cases.
Serum prolactin levels in both groups were less than 25ng/ml at daytime. In the patients with transient hyperprolactinemia, serum prolactin levels showed more than 150ng/ ml at 30 min. after the administration of 500μg of TRH, and those were less than 150ng/ml in the normal control group.
The daily changes of serum FSH, LH, prolactin, estradiol and progesterone levels were determined by radioimmunoassay in 6 cases of transient hyperprolactinemia and 5 controls which showed normal ovulatory cycles in the patterns of the BBT charts and other hormones. An estrogen feedback test was also carried out at the mid-luteal phase in 9 cases of transient hyperprolactinemia and the controls to determine serum levels of FSH, LH, prolactin and estradiol. In the patients with transient hyperprolactinemia, 5mg of bromocriptine was administered every day for more than 30 days, and the effects of bromocriptine on the changes in serum gonadotropin levels by the estrogen feedback test were also analysed.
Serum prolactin levels in the follicular, ovulatory and mid-luteal phases increased significantly in the patients with transient hyperprolactinemia, compared to the controls (p<0.005). The pattern of serum prolactin levels in the patients with transient hyperprolactinemia was almost synchronized with that of serum estradiol levels. There was also a significant correlation (r= 0.5782, p<0.005) between the prolactin and estradiol levels in the serum of the patients. The obvious change was not noted in serum prolactin levels during the menstrual cycle of the controls. No significant change in other hormones was observed during the cycle between these two groups. After the administration of estradiol benzoate (100pg/kg), serum estradiol levels increased markedly, serum prolactin levels increased with the similar change in serum estradiol levels, and serum prolactin levels in the patients with transient hyperprolactinemia were significantly higher compared to those of the controls (p<0.01-0.005). The responses of serum gonadotropin levels by the administration of estradiol benzoate had good positive and negative feedback effects in the patients with transient hyperprolactinemia as well as those of the control group. However, the response of serum gonadotropin levels by the estrogen feedback test was improved significantly with the treatment of bromocriptine in the patients with transient hyperprolactinemia (p<0.01-0.005).
These facts indicate that in the patients with transient hyperprolactinemia, the increase of serum prolactin occurs either in the physiological increase of serum estradiol levels or in the administration of exogenous estrogens, and also that there is no significant change in serum prolactin levels during the menstrual cycle in the normal control group which are not the so-called transient hyperprolactinemia. In addition, it is suggested that bromocriptine proves to be useful to improve the responses of serum gonadotropin levels by the estrogen feedback test in patients with transient hyperprolactinemia.

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The influence of aging on the steroid secretory capacity of the adrenal gland was evaluated by comparing data on young (age 20 to 21 years) with elderly (age 77 to 86 years) healthy male subjects. After the administration of ACTH-Z (1 mg, im) during the treatment of dexamethasone (1mg/day, for 2 days), blood samples were taken at time 0, 1, 2, 3, 6, 12 and 24h.
The mean basal levels of pregnenolone (P₅), 17-hydroxypregnenolone (170HP₅), dehydroepiandrosterone (DHEA), progesterone (P₄), 17-hydroxyprogesterone (170HP₄), androstenedione (A-dione) and aldosterone (Ald) gradually decreased with advance in age. Dexamethasone administration to the elderly men produced no significant fall in plasma P₄ and Aid. Plasma ACTH levels after ACTH-Z administration were significantly higher in the elderly men than the comparable levels in the young men. The apparent half-life of ACTH-Z in plasma was prolonged in the elderly men. For 3 hours after ACTH-Z injection, the responses of all plasma steroids, such as P₅, 170HP₅, DHEA, P₄, 170 HP₄, A-dione, Ald and cortisol (F), were significantly lower in the elderly men. When the 24-hour secretion rates of steroid hormones were compared by Δ area, which indicated the increased area for 24 hours after ACTH-Z administration, the secretion rate of F showed no significant difference between the two groups, but that of DHEA was significantly low in the elderly men. The 24-hour secretion rates of P5 and P₄ were not impaired and that of 170HP₄ was significantly high in the elderly men.
These results indicate that the steroidogenic response to ACTH decreases with aging, and that, in the elderly men, an apparent decrease in C₁₇, ₂₀lyase efficiency may be related in part to the decreased secretion of adrenal androgens.

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