With the recent advance in immunohistochemical and molecular-genetic techniques, all of the components of the renin-angiotensin system (RAS) have been shown to exist in the vascular tissue of various animal species as well as in humans. The author's group previously reported that angiotensin II (AII) was generated in the mesenteric arteries of several experimental rat models. Vascular All generation appears to be regulated independently of circulating renin levels, as suggested by the expression of tissue-specific angiotensinogen mRNA. In the light of recent reports that aldosterone may be synthesized in the cultured endothelial cells from bovine aorta, and that 11β-hydroxysteroid dehydrogenase (11β-HSD) plays a key role in determining the specificity in mineralocorticoid activity in various mineralocorticoid-responsive tissues, the author wishes to review the studies carried out by colleagues on the production of aldosterone with its precursor steroids and enzyme expression for aldosterone synthesis in the blood vessels as the components of the vascular auto-/para-crine system.
The first part of the present paper is summarized as follows: 1) With Northern blotting and RT-PCR of the RNA which was prepared from rat arterial tissue or cultured human arterial smooth muscle cells (SMC), the expression of mineralo- and glucocorticoid receptors was confirmed. 2) The vascular production of aldosterone and corticosterone from the rat mesenteric artery was demonstrated in analyzing the arterial perfusates using a HPLC and GC/MS. Moreover, in this ex vivo experiment, the production of aldosterone in the vasculature was found to be partially controlled by angiotensin II generated locally. 3) It was clearly demonstrated using an RTPCR method for the first time that aldosterone synthase, cytochrome P450aldo (c 18 or c mo); CYP 11B2 messenger RNA is expressed in the cultured endothelial cells (EC) from human pulmonary artery.
From these data, the author would like to propose the concept of a vascular renin-angiotensin-aldosterone system under which paracrinaly produced mineralocorticoid in the vascular EC may easily reach the vascular SMC and in turn act to increase the vascular tone through binding to the receptor there.
The second part can be summarized as follows: 1) The expression of 11β-HSD in the vasculature was confirmed by bioassay using ex vivo experiment of the isolated rat mesenteric artery perfusion system, immunocytochemical staining methods, in situ hybridization and also by Northern blot analysis. 2) The activity of 11β-HSD in the mesenteric arteries of SHR in the prehypertensive stage was lowered compared with WKY rats. Also, the activity of 11β-HSD in the mesenteric arteries of Dahl's salt-sensitive (SS) hypertensive rats was lowered compared to Dahl's salt-resistant (SR) rats. The former finding seemed to link with hyperadrenergic state in SHR and the latter to link with the salt sensitivity in SS rats. 3) From the clinical standpoint, 11β-HSD activity and 5β-reductase activity in patients with essential hypertension (EHT) were compared with those in matched normotensive controls. The activity of each enzyme was assessed by the ratios of tetrahydrocortisone (THE) to the sum of tetrahydrocortisol (THF) and allo-tetrahydrocortisol (αTHF), and the ratios of a THF to THF in urine. As a result, 11β-HSD activity was not lowered in EHT compared to the controls, but there was a positive correlation between 11β-HSD activity and 5β-reductase activity in only EHT. Moreover, 5β-reductase activity was significantly lowered in EHT compared to the controls.
According to the above results of experimental hypertensive rats and clinical data in essential hypertension, the hypothesis that the deficient inactivation of cortisol in the vasculature may cause hypertension was supported.

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TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO autoantibodies are very important to diagnose autoimmune thyroid disease and to estimate its clinical course. An EIA for measuring anti-TPO autoantibodies (rhTPO-EIA) was developed using recombinant human TPO expressed in CHO cells and was compared with MCHA generally used in routine laboratory work. Sera from patients with various disorders were measured for their anti-TPO autoantibodies. Chronic thyroiditis and Graves' disease were highly positive, while thyroid cancer, adenoma, SLE, and RA were low in their positivity. The positive rate of anti-TPO autoantibodies was compatible with those of previous reports of each disorder. In the comparison between rhTPO-EIA and MCHA, the correlation coefficient was 0.486. Following absorption with thyroglobulin, sera were measured again and as a result, the correlation coefficient increased to 0.723. Therefore, MCHA was thought to be influenced in the presence of anti-thyroglobulin autoantibodies. The characteristics of TPO antigen and anti-TPO autoantibodies were also summarized.

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The aim of the present study was to evaluate the time-dependent effect of an experimentally induced hypothyroid state on prolactin (PRL) secretion in rats.
Treatment with radioactive iodine and propylthiouracil (PTU) resulted in reduced serum concentrations of total thyroxine and triiodothyronine, and increased serum TSH concentrations in rats one week after the start of the treatment. Basal serum PRL concentrations were not significantly altered in 1-, 2- and 4-week hypothyroid rats, whereas in 8-week hypothyroid rats, serum PRL concentrations were significantly reduced and remained depressed throughout 24 weeks of PTU ingestion. The PRL response to i. p. administration of haloperidol (0.5mg/kg) was significantly reduced after one week of PTU ingestion. When the duration of hypothyroidism was increased, there was a progressive fall in the PRL response to haloperidol that reached the lowest value after 12 weeks of PTU ingestion. The PRL response to an i. v. bolus injection of vasoactive intestinal peptide (VIP, 150μg/kg) was markedly reduced in hypothyroid rats after one week of PTU ingestion and reached the lowest value after two weeks. The PRL response to VIP was progressively recovered after treatment for 4 weeks with PTU, and reached the highest value in 24-week hypothyroid rats. However, the PRL response to VIP in 24-week hypothyroid rats was significantly lower than that in euthyroid rats. Serum PRL response to an i. v. bolus injection of β-endorphin (450μg/kg) was significantly reduced in 8-week hypothyroid rats. Dopamine (DA) concentrations in the pituitary and the hypothalamus were not significantly altered in 2-week hypothyroid rats. In contrast, DA concentrations were significantly increased in both the pituitary and hypothalamus in 8- and 24- week hypothyroid rats. These findings observed in hypothyroid rats were reversed by the administration of thyroxine and triiodothyronine for 9 days.
The present results support a modulatory role for thyroid status in regulating the concentration of DA in the pituitary and the hypothalamus, and consequently on PRL secretion by the pituitary. This suggests that PRL releasing factors do not appear to play a major role in PRL secretion in hypothyroid rats. These data also indicate that alterations in PRL secretion and DA concentrations in the pituitary and the hypothalamus in the hypothyroid state become more prominent as the duration of hypothyroidism increases.

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A previously unknown HPLC peak was recently observed in urine samples from patients with Cushing's syndrome and disease.
We analysed dansylated derivatives of 17keto steroid glucuronides in urine samples from patients with Cushing's syndrome, Cushing disease and from healthy subjects using high-performance liquid chromatography (HPLC) on reversed-plase Cap Cell PakC8.
All urine samples from patients with Cushing's syndrome caused by adrenal adenoma and Cushing's disease showed an unknown large peak at the point between [110HE-G] and [110HA-G] peaks and at a retention time of 25.4 min. The same unknown peak was also observed in urine samples from a patient with asymptomatic cortisol-producing adrenal adenoma and two patients with ectopic ACTH-producing tumor, though the peak height was low for the former and one of the latter but high for the second of the two patients.
In contrast, healthy male and female urine only showed a very small peak at the same retention time.
Urine samples from a Cushing disease treated with op'DDD and Cushing's syndrome bilaterally adrena-lectomized and treating with cortisol showed no such peak.
The retention time of this unknown peak is clearly different from that of seven 17keto steroid standard glucuronide conjugates. The structure of this substance may be closely related to [110HE-G] or [110HA-G].

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The association between hormone dynamics and bone turnover was statistically examined in 52 women with surgically induced menopause. The mean values of 19 laboratory items which included hormones as well as parameters of bone metabolism were obtained and analyzed by Spearman's rank test. Linear regression models were established. Based on Pearson's correlation matrices, the principal components were analyzed. Metrics were formed from factor loading derived from Varimax's rotation, and their statistical significance was evaluated.
1. Significant correlations were determined from both the examination of the data analyzed separately at the levels of artificial menopause (bilateral and unilateral) and oophorectomy (OVX) method (bilateral or unilateral). For the patients who had bilateral OVX, the pairs showing a positive correlation (0.01<P, 0.05<P) were 1-25-(OH)₂D with E₂ or ASD, 25-(OH)D with E₂, E₃, Progesterone, or ASD, CT with Progesterone, ASD, or Testosterone, S.Al-P with FSH or LH, and S. Ca with LH. The pairs showing a weaker positive correlation were PTH with E₂ or E₃, CT with E₂, E₃ with S. Acid-P or U. Ca/CRN, and S. Ca with FSH. The pairs showing a negative correlation (0.01<P, 0.05<P) were S. Al-P with E₂ or Progesterone, and S. Ca with Testosterone. The pairs showing a weaker negative correlation were S. Al-P with ASD. For the patients who had unilateral OVX, the pairs showing a positive correlation were 1-25-(OH)₂D with E₂, ASD, or Testosterone, 25-(OH)D with E₂, E₃, Progesterone, or ASD, CT with Progesterone, ASD, or Testosterone, and PTH with ASD. The pairs showing a weaker positive correlation were PTH with E₂ or E₃, and CT with E₂. The pairs showing a negative correlation were S. Ca with Testosterone. The pairs showing a weaker negative correlation were S. Al-P with ASD. There was a small but significant difference between the two groups. However, Estrogen and Androgen in sex steroids, and S. Al-P, S. Ca, CT, PTH, 1-25-(OH)₂D, and 25-(OH)D in bone parameters, all changed early or late at different rates but participated concomitantly with the high bone turn-over induced by OVX, particularly in bilateral.
2. Significant correlations among all parameters were determined for data analyzed at the level of artificial menopause. For the patients who had OVX, the pairs showing a positive correlation were E₂ with 1-25-(OH)₂D or 25-(OH)D, E₃ with 25-(OH)D, Progesterone with 25-(OH)D or CT, ASD with 1-25-(OH)₂D, 25-(OH)D, CT, or PTH, Testosterone with 1-25-(OH)₂D, 25-(OH)D, or CT, FSH with S. Al-P, LH with S. Al-P or S. Ca, S. Al-P with S. Ca, S. P, or S. Acid-P, S. Ca with S. P or S. Acid-P, 25-(OH)D with 1-25-(OH)₂D or CT, U. Ca with U. P, and U. P/CRN with CT, U. Ca/CRN, or U. P. The pairs showing a negative correlation were S. Al-P with E₂ or Progesterone, Testosterone with S. Ca, ASD with FSH or LH, and CT with S. Ca or U. P. Through analysis of the principal components and Varimax's rotation after OVX, the indices were divided into pertinent groups, and their relationship was determined. FSH and LH formed one group which demonstrated an isodirectional relationship with S. Ca and S. P with S. Al-P acting as an intermediary. By contrast, this group showed a reverse directional relationship with E₂, 25-(OH)D, CT and Testosterone formed another group which had an isodirectional relationship with ASD and showed a reverse directional relationship with U. P, E₂, ASD, and 1-25-(OH)₂D made up another group. U. P/CRN, U. P, and S. Acid-P formed another group. U. Ca/CRN and U. Ca formed another group.

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