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Biomedical subjects

T Aono

Publications and source records attributed to T Aono.

At least 253 records · Page 14Linked to original sources

Monoamine oxidase in rat ovary during the estrous cycle. A histochemical study by a new coupled peroxidatic oxidation method.

A new coupled peroxidatic oxidation method for histochemical detection of monoamine oxidase (MAO) was applied to rat ovary. With this new method, fixed tissues could be used, and two forms of MAO could be identified by use of selective inhibitors. MAO activity was observed in the corpora lutea, interstitial gland cells, and blood vessels. In the corpora lutea, no activity was detected during the first estrous cycle, but strong activity was observed in the next two cycles. MAO in blood vessels showed characteristic changes of activity during the estrous cycle. The results suggest that MAO activity might possibly be involved in ovulation and progesterone metabolism in the ovary. Like other organs, rat ovary was found to contain two types of MAO; type A MAO was predominant in the corpora lutea. On the other hand, only one type of MAO, type B, was found in the blood vessels.

Animals↗

Effect of calmodulin inhibitors on thyroid hormone secretion.

The effect of calmodulin inhibitors, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine, on TSH-induced thyroid hormone secretion from rat thyroid was examined in vivo and in vitro. The ip administration of 5 mg W-7 to the rat inhibited T4 and T3 secretion from rat thyroids at 2, 3, and 4 h after the ip injection of 2 IU TSH, and so did the ip injection of trifluoperazine at 3 and 4 h. However, the ip injection of N-(6-aminohexyl)-1-naphthalene sulfonamide as a control substance did not show any significant inhibition of T4 and T3 release. To identify the site of action of calmodulin, the effect of W-7 on (Bu)2cAMP-induced thyroid hormone secretion was tested in vitro. One hundred micromolar W-7 completely inhibited T4 release from the rat thyroid when it was enhanced by TSH or (Bu)2cAMP, suggesting that the inhibitory effect of W-7 is subsequent to cAMP formation. These results suggest that calmodulin may play a role in thyroid hormone secretion from the thyroid, acting beyond cAMP formation.

Animals↗

Enolase subunits in patients with neuroendocrine tumors.

Concentrations of the alpha-, beta-, and gamma-subunits of enolase in surgically resected tumors and serum obtained from patients with various endocrine tumors were measured by a sensitive enzyme immunoassay system. Tissue concentrations of the gamma-subunit were significantly elevated in patients with neuroendocrine tumors concurrent with high concentrations of the gamma-subunit in their serum, which fell to normal in 90% of those who underwent tumor resection. Immunohistochemical analysis revealed that considerable amounts of the gamma-subunit were contained specifically in these tumors. These results indicate that the gamma-subunit of enolase is a useful marker for diagnosing and monitoring patients with neuroendocrine tumors.

Adult↗

Clomiphene citrate induces pituitary GnRH receptors in ovariectomized rats: its possible role in induction of ovulation.

Since our previous studies have shown that clomiphene citrate (clomiphene) acts directly on the pituitary gland and exerts a facilitatory role on oestradiol-17 beta (E2)-induced LH surge in chronically ovariectomized rats, the effect of clomiphene on pituitary GnRH receptors was investigated. A single ip injection of either 5 micrograms E2 or 200 micrograms clomiphene did not induce LH release in adult rats ovariectomized 1-2 weeks before the injection. However, a significant increase in serum LH was noted 24 h after a single injection of E2 in the ovariectomized rats, if clomiphene was pre-injected 48 h before the E2 injection. The content of pituitary GnRH receptors in the ovariectomized rats (62 +/- 9 fmol/pituitary) remained almost unchanged until 24 h after a single injection of clomiphene but significantly increased 48 h after the injection (105 +/- 13 fmol/pituitary) without any alterations in the affinity for GnRH. To determine steroid specificity for the increase in pituitary GnRH receptors, other classes of steroids were injected in the ovariectomized rats. A single dose of E2 increased GnRH receptors, but either progesterone or 5 alpha-dihydrotestosterone failed to show any effect on the level of GnRH receptors. These results suggest that clomiphene may augment oestrogen-induced pre-ovulatory LH surge in anovulatory women, at least in part by increasing the number of pituitary GnRH receptors.

Animals↗

Dexamethasone inhibits the effects of oestrogen on the pituitary gland in rats.

The administration of glucocorticoids has been shown to be effective for the induction of ovulation in patients with anovulation. In the present study, we investigated the effects of a glucocorticoid on oestrogen-induced changes in the pituitary gland. A single ip injection of 10 micrograms oestradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant increase in pituitary weight and progesterone receptor (PgR) concentration. In these animals, serum LH level was initially suppressed and restored to control level 24 h after E2 injection. However, 1 mg of dexamethasone (Dex) injected before E2, but not after E2 administration, completely inhibited both the increases in pituitary weight and PgR concentration. The restoration of serum LH level 24 h after E2 was also prevented. These antioestrogenic effects of Dex were blocked by ip administration of the synthetic antiglucocorticoid, RU486. Dex treatment alone did not have any effect on E2-induced changes in the dynamics of pituitary oestrogen receptor. Finally, E2-pellet implanted sc in ovariectomized and adrenalectomized rats for 7 days caused marked increases in pituitary weight and PgR concentration. A single ip injection of 250 micrograms clomiphene citrate (clomiphene) significantly reduced both the pituitary weight and PgR concentration in these animals, but 1 mg of Dex failed to have a similar effect. These results suggest that glucocorticoids antagonize E2 effects on the pituitary by a mechanism different from antioestrogens such as clomiphene. These antioestrogenic effects of glucocorticoid may be involved in induction of ovulation in anovulatory women.

Adrenalectomy↗

Histochemical studies on human placental and chorionic monoamine oxidase.

A new coupled peroxidation method for detection of monoamine oxidase was applied to human chorionic and placental tissues of various weeks of gestation. With this new method, the precise localization of monoamine oxidase activity could be determined and the two isotypes of the enzyme could be identified using selective inhibitors. Significant monoamine oxidase activity was observed in syncytiotrophoblasts of fine villi and budding villi. Monoamine oxidase activity in chorionic and placental tissues remained similar in intensity and localization throughout pregnancy. Only one type of monoamine oxidase, type A, was found in the placenta. The functional role of monoamine oxidase is discussed.

Chorion↗

Effects of bromocriptine on prolactin-secreting pituitary adenomas. Mechanism of reduction in tumor size evaluated by light and electron microscopic, immunohistochemical, and morphometric analysis.

Prolactin-secreting pituitary adenomas were studied to clarify the mechanism by which bromocriptine reduces tumor size. Patients examined consisted of three groups: Group I (four cases) received no medication, Group II (six cases) continued bromocriptine treatment (10 mg/day for 2 weeks) until the operation, and Group III (five cases) discontinued the treatment 1 week before the operation. Adenomas in Group II showed a variety of degenerative and necrotic changes of tumor cells in addition to marked decrease in volume of individual cell. Adenomas in Group III showed divergent structural changes. Irreversible changes seen in Group II became more pronounced with a marked increase in stromal tissue. Proliferative areas consisting of intermediate-sized cells were found in the scarce stromal tissue. The findings seem to indicate that the reduction in size of prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as from cell loss secondary to necrosis.

Adenoma↗

Dopamine decreases release of luteinizing hormone releasing hormone from superfused rat mediobasal hypothalamus.

The effects of dopamine hydrochloride (DA) on the releases of LHRH and LH were examined in a serial sequential double chamber perifusion system by perifusing the mediobasal hypothalamus including the preoptic area and/or pituitaries excised from diestrus female rats. DA, perifused at a dose of 4.2 X 10(-4) M, significantly (p less than 0.05) lowered LH secretion from the pituitary in series with the hypothalamus 40-80% below the preinfusion level, but it had no effect on LH efflux from the pituitary perifused alone. DA also significantly (p less than 0.05) reduced the LHRH level 20-40% below the initial level. Perifusion with the DA receptor blocker haloperidol at a concentration of 10(-6) M abolished the suppressive effect of DA on LH secretion. These findings indicate that DA suppressed hypothalamic LHRH release, resulting in decrease in LH secretion from the pituitary in diestrus rats.

Animals↗

Presence of two types of estrogen binding sites in mouse testis.

The characteristics of cytosol estrogen binding sites in BALB/c mouse testis were investigated. The cytosol prepared from the whole testis contained two classes of the specific estrogen binding sites by Scatchard and Rosenthal plot analyses. The first binding site (first binder) had high affinity for 17 beta-estradiol (E2; Kd = 4.9 X 10(-9) M) and binding specificity as observed in the typical estrogen receptor. The second binding site (second binder) had lower affinity for E2 (Kd = 4.8 X 10(-8) M) and the binding was inhibited less vividly by diethylstilbestrol (DES) and antiestrogens in comparison with that for the first binder. Postlabeled sucrose density gradient analysis in a low salt medium revealed that the major radioactive peak of the first binder appeared at 7S region, while that of the second binder sedimented at 4S region. The 7S component showed an appreciable binding to the nuclei, while the 4S component did not show a significant binding ability to the nuclei. Much higher concentrations of the first and the second binders were found in Leydig cells preparations. These results demonstrate the presence of two types of the specific estrogen binding sites in the mouse testis especially in Leydig cells.

Animals↗

Replenishment of uterine estrogen receptor in chronically estrogenized rats.

Replenishment of uterine estrogen receptor (ER) following a single injection of estradiol-17 beta (E2) was examined in chronically estrogenized rats. Subcutaneous implantation of E2-pellet for 7 days in ovariectomized rats resulted in a significant stimulation of uteri with regard to wet tissue weight, DNA content and progesterone receptor content, with a shift of ER distribution. An intraperitoneal injection of 5 micrograms E2 in the E2-implanted rats induced a significant decrease in soluble ER (from 141.1 +/- 12.6 to 69.2 +/- 8.8 fmol/mg protein) with a concomitant increase in nuclear ER (from 58.2 +/- 8.6 to 129.2 +/- 11.6 fmol/100 micrograms DNA) 1 h after the injection. However, soluble ER was rapidly replenished, which was accompanied by nuclear ER reduction, and both values returned to the pre-injection levels at 4 h after the injection. An administration of 150 micrograms cycloheximide, that effectively blocked protein synthesis in the uterus of the E2-implanted rats, completely inhibited the replenishment of soluble ER induced by 5 micrograms E2. These findings, combined with our previous findings that replenishment of ER following a single E2 administration in the pituitary of chronically estrogenized rats was inhibited by cycloheximide, suggest that replenishment of ER is entirely dependent on protein synthesis in chronically estrogenized rats.

Animals↗

Dexamethasone suppresses estrogen action at the pituitary level without modulating estrogen receptor dynamics.

The administration of glucocorticoid combined with antiestrogen such as clomiphene has been shown to be effective for the induction of ovulation in patients with anovulation. The present study was undertaken to examine the effects of glucocorticoid on estrogen-induced changes in the pituitary gland. A single intraperitoneal (i.p.) administration of 10 micrograms estradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant stimulation of pituitaries with regard to wet tissue weight and progesterone receptor content. An i.p. administration of 1 mg dexamethasone in these animals had no effects on both the values. However, the E2-induced increases in pituitary weight and progesterone receptor content were significantly inhibited by pretreatment with 1 mg of dexamethasone. The pretreatment with dexamethasone, on the other hand, had no significant effect on the dynamics of pituitary estrogen receptor induced by the injection of E2, i.e. the degree of nuclear translocation, occupancy and cytoplasmic receptor replenishment. The inhibitory effect of dexamethasone, therefore, does not seem to be mediated through estrogen receptor system in the pituitary. These results suggest that dexamethasone acts directly on the pituitary gland to suppress the action of E2, and which may be involved in the process of induction of ovulation by glucocorticoid-clomiphene treatment.

Adrenalectomy↗

The effect of lisuride hydrogen maleate on anterior pituitary hormones, oestradiol and cortisol in normal and hyperprolactinaemic women.

The effects of single oral doses of 0.1 mg lisuride hydrogen maleate (lisuride), a semisynthetic ergot derivative given at 09.00 h, on the serum levels of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyroid-stimulating hormone (TSH), oestradiol and cortisol were studied in six normally cycling women and six patients with hyperprolactinaemic amenorrhoea. The same subjects received placebo and the results were compared with those of lisuride. Within 1 h after oral administration of lisuride, PRL levels decreased significantly (P less than 0.05) and reached the lowest level at 4 h after ingestion and stayed low until 8 h in both normal women and hyperprolactinaemic patients. LH levels slightly but not significantly decreased after lisuride administration in hyperprolactinaemic patients. Serum cortisol levels increased at 13.00 h, probably due to the effect of meal. No significant differences between the lisuride group and placebo group were observed in GH, TSH, FSH and oestradiol levels. These results suggest that lisuride acts as a long-acting prolactin suppressor and that it has little effects on the secretion of other pituitary hormones. Therefore, this drug could be useful for treatment of hyperprolactinaemic patients.

Adult↗

Results of HMG (Humegon)-HCG therapy in 6096 treatment cycles of 2166 Japanese women with anovulatory infertility.

The effects of HMG (Humegon)-HCG therapy in 6096 cycles in 2166 Japanese women with anovulatory infertility were examined. The rates of ovulation, pregnancy, the ovarian hyperstimulation syndrome, multiple pregnancy, abortion, and malformations in the newborn were recorded, and the possible factors of multiple pregnancies were analyzed. Ovulation occurred in 73.2% of the cases and 64.5% of the treatment cycles. Pregnancy occurred in 23.0% of the cases and 8.6% of the cycles. Ovarian hyperstimulation syndrome with grade I of WHO definition or more was observed in 10.3% of the cases and 5.3% of the cycles. The incidence of the ovarian hyperstimulation syndrome was high in amenorrheic patients, who respond to progestin with bleeding. The multiple pregnancy rate was 20.5%, of which 13.0% was twins and 7.5% triplets or more. The abortion rate was 22.0%, and the abortion rate in multiple pregnancy was significantly higher (P less than 0.05) than that in singleton pregnancy. The external malformation rate was 1.68% in the 594 newborn who could be examined. No significant differences were found in maternal factors, the treatment schedule, or the ovarian response to treatment in singleton and multiple pregnancy groups. This survey revealed that the efficacy and the incidence of adverse effects of Humegon-HCG therapy in a large number of Japanese women were not different from those in Caucasians except for a lower rate of multiple pregnancy, and no special causative factors for multiple pregnancy were found.

Abnormalities, Drug-Induced↗

Down-regulation of testicular follicle-stimulating hormone receptors by human menopausal gonadotropin in infertile men.

We measured testicular FSH receptors in 27 infertile men before, or 1, 3, 5, 7, or 14 days after a single administration of 150 IU of hMG. The administration of hMG reduced Bmax for FSH receptors to about 50% of that in the preadministration testes for 5 days. From the seventh day, Bmax of FSH receptors began to increase and returned to the preadministration level 14 days after the administration.

Binding Sites↗