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Volume 64, Issue 6
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1988 Volume 64 Issue 6 Pages 439-449
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSDownload PDF (926K) -
Motoko OJIMA, Shigeatsu HASHIMOTO, Nobuo ITOH, Yoshiro KUSANO, Koji SA ...1988 Volume 64 Issue 6 Pages 451-462
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSO, p′-DDD has a cytotoxic action and inhibites the cholesterol side chain cleavage enzyme, 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase and 21-hydroxylase of the adrenal cells. However, the effects of o, p′-DDD on gonadal steroidogenesis are still unknown. In the present study, the effects of o, p′-DDD on Plasma cortisol, pregnenolone, 17α-hydroxypregnenolone (17-OH-pregnenolone), progesterone, 17α-hydroxyprogesterone (17-OH-progesterone), 11-deoxycorticosterone (DOC), corticosterone, dehydroepiandrosterone (DHEA), delta 4-androstenedione (androstenedione), estradiol, and LH and FSH were investigated in 3 patients with Cushing's disease before and after the administration of o, p′-DDD. The results are presented here.
In Case 1 (18 yr old female) who had had secondary amenorrhea for 2 years, the plasma levels of cortisol, pregnenolone, 17-OH-pregnenolone, DHEA, androstenedione, testosterone, estradiol and corticosterone were elevated. The basal levels of plasma LH and FSH and the responses of both gonadotropins were lower than those of women with eumenorrhea. The plasma levels of progesterone, DHEA and testosterone decreased to normal 2 months after the beginning of the administration of o, p′-DDD. She restored menstrual cycles ranging from 40 to 50 days 3 months after the administration of o, p′-DDD, but with anovulatory bleeding. She showed a biphasic body temperature pattern with plasma progesterone and estradiol levels indicating corpus luteum formation 11 months after the start of the treatment, when plasma cortisol as well as progesterone and androgen were reduced to normal. The basal levels of FSH and LH and responses of these gonadotropins were slightly improved at that time.
The plasma levels of cortisol, DHEA and androstenedione were high in Case 2 (38 yr old male) and Case 3 (45 yr old male), whereas plasma testosterone level was normal in Case 2 and low in Case 3. The plasma levels of these 3 steroids were normalized 28 days after the beginning of the o, p′-DDD administration.
These results suggest that o, p′-DDD does not interfere with gonadal steroidogenesis in Cushing's disease.View full abstractDownload PDF (1003K) -
Osamu MIMURA, Hajime MORIKAWA, Mineo YAMASAKI, Matsuto MOCHIZUKI1988 Volume 64 Issue 6 Pages 463-481
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSIn order to elucidate the mechanism of pregnancy-induced hypertension (PIH) from the point of view of vascular resistance, we measured the intracellular Na+ concentrations and the membrane Na+ effluxes using red blood cells from normal pregnant females and patients with PIH. We also discussed the influences of hormones such as estrogen, progesterone, dehydroepiandrosterone sulfate (DHAS), hydrocortisol, human placental lactogen (hPL), human chorionic gonadotropin (hCG), and prolactin and parathyroid hormone (PTH) on the membrane Na+ effluxes. The intracellular Na+ concentrations were lower and the Na+-K+ ATPase activities were slightly higher both in the luteal phase and in the first trimester of normal pregnancy than those in the follicular phase, after which the former gradually increased and the latter gradually decreased until term to the mean values of those in the whole menstrual period. In mild PIH, the intracellular Na+ concentrations were not significantly increased, and the Na+-K+-ATPase activities were significantly increased compared to those in the third trimester of normal pregnancy, which suggests the compensatory increase of the Na+-K+-ATPase activities as opposed to the increase of the intracellular Na+ concentrations. In severe PIH, the intracellular Na+ concentrations were significantly increased compared with those in the third trimester of normal pregnancy and slightly increased compared with those in mild PIH, whereas the Na+-K+-ATPase activities were slightly decreased compared with those in mild PIH, which indicates a breakdown of the compensatory in-crease of the Na+-K+-ATPase activities. The intracellular Na+ concentrations in PIH are significantly correlated to diastolic pressure, systolic pressure and mean blood pressure.When the male red blood cells were incubated with the hormone, dose-dependently the Na+-K+-ATPase activities were significantly elevated by hydrocortisol and slightly elevated by progesterone and hPL, and they were significantly depressed by estrogen and prolactin and slightly depressed by PTH. These results suggest that the peripheral vascular resistance might be increased in the third trimester of normal pregnancy compared with that in the first trimester because the intracellular Na+ concentrations were elevated, and the Na+-K+-ATPase activities in the cell membrane were decreased along the course of pregnancy as a result of the effects of various hormones in the maternal blood. In mild PIH the peripheral vascular resistance might be increased compared with that in the third trimester of normal pregnancy because of the elevation of the intracellualr Na+ concentrations in spite of the compensatory increase of the Na+-K+-ATPase activities. However, in severe PIH the Na+-K+-ATPase activities were decreased as a result of the actions of the increased prolactin and PTH and the decreased estrogen and hPL in the maternal blood, and therefore the intracellular Na+ concentrations became more significantly increased than those in mild PIH, and the symptoms might be more severe than those of mild PIH.View full abstractDownload PDF (1668K) -
Atsumi YAMAGUCHI, Tadayuki ICHIMURA, Tooru YAMABE1988 Volume 64 Issue 6 Pages 482-488
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSIt is considered that plasma-free testosterone is a bioactive androgen in blood and is more reflective in androgenicity than plasma total testosterone. We measured plasma-free testosterone by dializable method in normal menstrual females, pregnant females, post menopausal females and vulvar dystrophy.
The values of plasma total testosterone (T), fractional free testosterone (%FT) and plasma-free testosterone (free T) were 0.61 ± 0.27 (mean ± SD) ng/ml, 1.19 ± 0.34% and 0.61 ± 0.20ng/dl in the follicular phase of normal menstrual females (n=25), and 0.57 ± 0.23ng/ml, 1.29 ± 0.46% and 0.56 ± 0.35ng/dl in the luteal phase of normal menstrual females (n=24), respectively. The values in both phases showed no differences from each other. In post menopausal females (n=18), the concentration of T (0.36 ± 0.27ng/ml) and free T (0.52 ± 0.12ng/dl) was significantly lower (T : P<0.01, free T : P<0.05) than that in normal menstrual females. However, %FT in post menopausal females (1.37 ± 0.12%) was not different as compared with that in normal menstrual females. In pregnant females (n=2) of second and third trimester, T (0.53 ± 0.07ng/ml) was not different as compared with that in normal menstrual females, but %FT (0.67 ± 0.45%) and free T (0.33 ± 0.23ng/ dl) were significantly lower (P<0.05) than in normal menstrual females.
In vulvar dystrophy, lichen sclerosus (n=19) and hyperplastic dystrophy without atypia (n=12) were measured. In these patients, T, %FT and free T were 0.82 ± 0.22ng/ml, 1.54 ± 0.88% and 1.33 ± 0.46 ng/dl in lichen sclerosus, and 0.76 ± 0.35ng/ml, 1.10 ± 0.22% and 0.95± 0.50ng/dl in hyperplastic dystrophy without atypia, respectively. T and free T in these patients were significantly higher (T : P<0.01, free T : P<0.05) than in post menopausal females. However, %FT was not different as compared with that in post menopausal females.View full abstractDownload PDF (660K) -
Mutsuko TAKEUCHI, Hajime MORIKAWA, Yasuo UEDA, Matsuto MOCHIZUKI1988 Volume 64 Issue 6 Pages 489-505
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSStudies in human as well as animal experiments have proved that IGF-1/SMC, which shows mitogenic activities in a wide variety of cell types, stimulates growth in vitro and in vivo. The aim of this study was to investigate the roles of IGF-1/SMC on fetal growth during pregnancy by measuring IGF-1/SMC, insulin, C-peptide, human placental lactogen (hPL), and GH and PRL concentrations in maternal and fetal plasma, and by clarifying the changes of IGF receptor in human fetal liver microsomal membranes during pregnancy.
Maternal plasma IGF-1/SMC concentrations were not distinguishable from those of nonpregnant women (9.2±1.7nmol/l) in the 1st and 2nd trimester of gestation; however, they showed a gradual increase after the 30th week of gestation, reaching 12.7 ± 5.4 at term. They possessed a significant positive correlation with hPL (r=0.45, p<0.05) and PRL (r=0.38, p<0.05) but not with GH (r=-0.39, NS). On the other hand, IGF-1/SMC in cord plasma could be first detected in the 30th week of gestation, and it increased gradually until term but had no significant correlation with that in maternal plasma. Furthermore, it possessed an intimate correlation with C-peptide (r=0.30, p<0.05) but not with GH or PRL. Additionally, IGF-1/SMC in cord plasma had a positive correlation with birth weight (r=0.60, p<0.005).
On the other hand, specific binding of 125I-IGF-1 and-II to liver microsomal membranes which was also displaced by nonlabeled insulin could be detected in human fetuses at various gestational ages.
Scatchard analyses indicated that the binding affinity, which was 0.14 ±0.05 (× 109M-1) in the fetal liver before the 19th week of gestation, increased after the 19th week of gestation (0.58 ± 0.12); conversely, the binding capacity was lower after the 19th week of gestation (0.15 ± 0.08 × 10-12 moles/mg protein) compared with that before the 19th week (0.51 ± 0.25).
These results suggest that (1) plasma IGF-1/SMC might be produced in fetal sites and its regulating mechanism is different from that in maternal sites, and that (2) IGFs might play an important role in human fetal growth and development by its affect via IGF or insulin receptors on the human fetal liver.View full abstractDownload PDF (1364K) -
Mitsuhiro NISHIMURA, Kenjiro KIKUCHI, Satoshi SATO, Kunio SAWAI, Izumi ...1988 Volume 64 Issue 6 Pages 506-513
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSIn order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60° head-up tilt (tilt) and an intravenous infusion of 1000ml 0.9% saline for 2 hours.
Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased.
On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed.
From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.View full abstractDownload PDF (710K) -
Kenichi SATOMURA, Hiroyuki TANAKA, Yoshiki SEINO, Makoto ISHIDA, Kanji ...1988 Volume 64 Issue 6 Pages 514-522
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSThe advance in knowledge of clinical disorders involving calcium and bone diseases has resulted in part from the development of assay procedures for the major vitamin D metabolites, but the values of the same samples measured in different laboratories vary considerably. They suggest that the chromatographic purification involved in these assays seems to be a critical step. In this study, we compared the results of 1, 25-dihydroxyvitamin D (1, 25 (OH) 2D) using different chromatographic purification methods : Sephadex LH-20 column chromatographic purification (non-HPLC method) described by Mallon et al. and High Performance Liquid Chromatographic purification (HPLC method) modified by Yamaoka et al.
Serum 1, 25 (OH) 2D levels of healthy volunteers before and after oral load of 4μg of la-hydroxyvitamin D3 (1αOHD3) were measured by the two different methods mentioned above. A good correlation (r=0.951, p<0.001) was noted in the samples before loading. The mean values of serum 1, 25 (OH) 2D before loading did not differ significantly between HPLC method and non-HPLC method. After loading, however, the mean value of serum 1, 25 (OH) 2 D was significantly higher in non-HPLC method (p<0.01).
The values of 1, 25 (OH) 2D were determined in the serum added 1, 25-dihydroxy-24-oxo-vitamin D3 (24-oxo-D3) (Opg/ml, 200 pg/ml or 2000 pg/ml). In the samples added 2000pg/ml of 24-oxo-D3, the mean value of 1, 25 (OH) 2D was significantly higher in non-HPLC method (p<0.001).
The affinity of 24-oxo-D3 for 1, 25 (OH) 2 D3 cytosolic receptor was evaluated in chick embryo intestinal mucosa and rachitic chick intestinal mucosa. 24-oxo-D3 showed an affinity 1/3.7 of 1, 25 (OH) 2D3 for chick embryo receptor and 1/9.4 for rachitic chick receptor.
These data suggest that significant amounts of interfering substances which have a high affinity for 1, 25 (OH) 2D3 receptor are present in the samples from humans treated with 1αOHD3 and purified by Sephadex LH-20 column chromatography.View full abstractDownload PDF (735K) -
Takashi MATOZAKI, Choitsu SAKAMOTO, Munehiko NAGAO, Hogara NISHIZAKI, ...1988 Volume 64 Issue 6 Pages 523-530
Published: June 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSOur previous study concerning guanine nucleotides regulation of labeled somatostatin binding has suggested that somatostatin receptors on pancreatic acinar cell membranes probably couple with the inhibitory guanine nucleotide regulatory protein (Ni). In order to clarify the possible role of Ni in mediating signal transduction of somatostatin in the pancreas, we further examined the effect of pretreatment with islet activating protein (IAP) on the inhibition of VIP-stimulated cellular cyclic AMP content by somatostatin in isolated rat pancreatic acini. Increasing concentrations of somatostatin decreased VIP-stimulated cellular content of cyclic AMP in the acini, with a maximal inhibition at 10-8M somatostatin. When pancreatic acini were pretreated with varying concentrations of IAP for 4 hours, the somatostatin-induced inhibition of cyclic AMP content was attenuated in a dose dependent manner by IAP pretreatment. Incubation of pancreatic acinar membrane with preactivated IAP and [32P] NAD resulted in labeling of a Mr=41000 protein band, consistent with α-subunit of Ni in many other cell types previously reported. On the other hand, a Mr=41000 protein band on SDS gel was reduced in a dose dependent fashion by IAP pretreatment, when acini were pretreated with increasing concentrations of IAP. These results suggest that only the Mr=41000 protein is a specific substrate in pancreatic acinar' membranes for TAP-induced ADP-ribosylation. Futhermore, the reduction of 32P incorporation to Mr=41000 protein by IAP pretreatment occurred in parallel to decreases in somatostatin-induced inhibition of cellular cyclic AMP contents in pancreatic acini.
These results suggest that pretreatment of acini with IAP reverses the inhibitory effect of somatostatin on VIP-stimulated cyclic AMP content via ADP-ribosylation of the Mr=41000 protein (a subunit of Ni). In conclusion, our accumulated data suggest that Ni may play an important role in mediating the inhibitory action of somatostatin on adenylate cyclase enzyme system in pancreatic acini.View full abstractDownload PDF (960K)
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