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Biomedical subjects

T Aono

Publications and source records attributed to T Aono.

At least 271 records · Page 15Linked to original sources

Serum cyclic 3',5'-nucleotide phosphodiesterase in patients with various thyroid disorders.

Previous observations that cyclic 3',5'-nucleotide phosphodiesterase activity exists in mammalian sera including human serum prompted us to investigate the phosphodiesterase levels in sera of patients with various thyroid disorders. Both serum cyclic AMP phosphodiesterase (cAMP-PDE) and cyclic GMP phosphodiesterase (cGMP-PDE) activities measured in a low substrate concentration were elevated 3-fold in subacute thyroiditis and slightly in hyperthyroidism, compared to the normal. Slight decreases of these enzyme activities were observed in primary hypothyroidism. PDE activities were positively correlated with the value of T3-RSU and serum thyroid hormone levels in hyper- and hypothyroidism. Altered enzyme activities returned to normal during the course of recovery. Identical results were obtained when plasma was tested. These results suggest that serum PDE activities may be partly related to the thyroid function.

3',5'-Cyclic-AMP Phosphodiesterases↗

Suppressive effect of prolactin on oestrogen-induced secretion of LH by sequentially perifused rat hypothalamus-pituitary.

The effect of prolactin (Prl) on oestrogen-induced gonadotrophin secretion was examined in vitro in a sequential double chamber perfusion system. As control groups, mediobasal hypothalamus (MBH)-pituitary pairs or pituitaries without the MBHs were perifused with Medium 199. As an experimental group, MBH-pituitary pairs were perifused with Medium 199 containing 1 micrograms/ml of rat Prl. These groups were stimulated with 10(-7) M oestradiol-17 beta (E2) for 30 min, and luteinizing hormone (LH) in the serial fractions of effluent was measured. In the control group of MBH-pituitary pairs perifused with medium without Prl, secretion of LH began to rise within 30 min after the beginning of stimulation, reached a peak 30 min after the end of stimulation and then remained at a plateau for the rest of the experimental period, whereas in the control group of pituitaries alone no significant response was observed. In the experimental group perifused with medium containing Prl, LH-secretion showed peaks 20 and 80 min after the end of E2-stimulation, respectively, and the first peak was significantly (P less than 0.01) less than the level in the control group. These data demonstrate that Prl at this concentration suppressed the rapid LH release induced by E2. Its site of action is suggested to be at the hypothalamic level, and its possible mechanism of action is discussed.

Animals↗

Epidermal growth factor stimulates secretion of rat pituitary luteinizing hormone in vitro.

The effects of epidermal growth factor (EGF) on pituitary luteinizing hormone (LH) release and on the releases induced by oestradiol (E2) and LH-releasing hormone (LRH) were examined in a sequential double chamber perifusion system. In this system the mediobasal hypothalami (MBH) and/or pituitaries excised from normally cycling female rats in dioestrus were perifused with test media. Perifusion with EGF at 1 ng/ml for 30 min induced significant release (80-100% increase, P less than 0.05) of LH from hypothalamo-pituitary pairs, but not from the pituitary alone. Perifusion of the pituitary alone with medium containing 1 ng/ml EGF, resulted in significant release of LH (70-140% increase, P less than 0.05) after administration of 10(-7) M E2, but did not significantly influence LH release in response to 20 ng/ml LRH. These findings suggest that EGF may be involved in the regulation of pituitary gonadotrophin secretion by a direct effect on the hypothalamus and indirectly by increasing the pituitary responsiveness to E2.

Animals↗

Possible site of negative and positive feedback action of oestrogen on gonadotrophin secretion in normal women.

For determination of the site of action of oestrogen (E) during the negative and positive feedback phases of gonadotrophin secretions, studies were made on the pituitary response to a small amount of LRH and the pulsatility of gonadotrophins after E administration in normal cycling women in the mid-follicular phase. The pituitary responses to an iv bolus of 2.5 micrograms of synthetic LRH were evaluated by measuring serum LH and FSH 2 h before and 8 h after administration of 20 mg of conjugated E (Premarin). In the next cycle, the pituitary responses to a same dose of LHRH were also observed 2 h before and 56 h after E injection. The mean levels of serum LH and FSH and the peak responses to LRH were significantly (P less than 0.05) decreased 8 h after E injection, but were significantly (P less than 0.05) increased 56 h after E administration. In the third cycle, the pulsatility of gonadotrophins was evaluated by measuring serum LH and FSH every 15 min for 180 min before and 8 h and 56 h after E injection. The pulse frequencies of gonadotrophins were not significantly different before and 8 h and 56 h after E injection. The amplitudes of pulses 56 h after Premarin injection were significantly higher than those before the injection. These findings suggest that the negative and positive feedback effects of E on gonadotrophin secretion may be caused, in part, by its direct action on the pituitary response to LRH.

Adult↗

A possible role of clomiphene citrate in the control of pre-ovulatory LH surge during induction of ovulation.

A possible role of clomiphene citrate (clomiphene) in the control of ovulation in anovulatory women was investigated. Since a single ip administration of 5 micrograms oestradiol-17 beta (E2) to long-term ovariectomized rats did not induce LH surge, the following studies were designed to determine whether pretreatment with clomiphene followed by administration of E2 could induce LH surge in the ovariectomized rats. Changes in cytoplasmic and nuclear oestrogen receptors (ER) were also examined in the pituitaries of these animals. An ip injection of 200 micrograms clomiphene suppressed serum LH levels significantly for 72 h. The clomiphene injection rapidly caused an elevation of nuclear ER with a concomitant depletion of cytoplasmic ER level in the pituitary and the ER levels remained almost unchanged for 72 h. An administration of E2 12 or 24 h after the clomiphene injection had no significant effects on either the serum LH levels or the cytoplasmic and nuclear ER levels, compared with those induced by clomiphene alone. However, LH surge and the depletion of nuclear ER in the pituitary occurred 24 h later when E2 was injected 48 h after the clomiphene administration. The E2-induced LH release seems to be induced by a replacement of clomiphene by E2 on the nuclear receptor complex. These results suggest that clomiphene may exert actions directly on the pituitary gland to augment oestrogen-induced LH release.

Animals↗

Prolactin inhibits oestradiol-induced luteinizing hormone release at the pituitary level.

The direct action of prolactin (Prl) on pituitary LH secretion was studied by examining its effect on oestradiol (E2)-induced luteinizing hormone (LH) release from the rat pituitary in a perifusion system and determining the oestrogen receptor (ER) content of the pituitary in hyperprolactinaemic female rats. When the pituitary from rats in pro-oestrus was perifused with medium alone, 10(-7) M E2 significantly (P less than 0.05) increased the LH concentration in the effluent by 60-130% of the basal level, but in medium containing 1 microgram/ml Prl it did not cause LH release. In hyperprolactinaemic rats produced by implanting 2 anterior pituitary glands under the kidney capsule, the ER content of the cytosol of the pituitary (53.2 +/- 2.9 fmol/pituitary) was significantly increased (P less than 0.05), but that of the nuclei (6.8 +/- 0.2 fmol/pituitary) was significantly decreased (P less than 0.05) compared with the contents in rats in pro-oestrus. These data suggest that Prl has a direct suppressive effect on LH secretion from the pituitary in the rat, and that decreased translocation of ER into the nucleus might relate to impaired LH release by E2 from the pituitary of hyperprolactinaemic rats.

Animals↗

Decrease of LRH receptors in the pituitary gland in streptozotocin-induced diabetic rats.

In studies into the mechanism of anovulation in the diabetic condition, the LRH receptor content of the pituitary gland of rats with diabetes mellitus was determined. Normal female rats weighing 180-200 g were injected iv with either streptozotocin (6 mg/100 g body weight) or vehicle in dioestrus of the oestrous cycle. The rats were sacrificed by decapitation 9 days after treatment, and serum LH concentrations and the LRH content of the medial basal hypothalamus (MBH) were measured by radioimmunoassay (RIA), and the LRH receptor content of the pituitary gland was determined. The serum concentration of LH and the LRH content of the MBH in diabetic rats were 34.4 +/- 4.8 ng/ml (mean +/- SEM) and 2.05 +/- 0.04 ng/MBH, respectively, which were similar to the respective values of normal rats in dioestrus. However, the LRH receptor content of diabetic rats (13.2 +/- 3.9 fmol/pituitary) was significantly (P less than 0.05) lower than that of normal rats in dioestrus (68.0 +/- 7.1 fmol/pituitary) and pro-oestrus (59.4 +/- 13.6 fmol/pituitary). These results suggest that anovulation in diabetic rats is at least partly attributable to a low content of LRH receptors in the pituitary gland.

Animals↗

Effect of hypophysectomy on cyclic 3',5'-nucleotidemetabolizing enzymes in the rat thyroid gland.

Adenylate cyclase and cyclic AMP phosphodiesterase activities in the thyroid gland were significantly reduced after hypophysectomy, followed by a gradual restoration of the enzyme activities to the levels seen in sham-operated rats whereas a slight and persistent reduction was evident in guanylate cyclase and cyclic GMP phosphodiesterase activities in the same tissue. These changes in enzyme activities were restored by TSH administration but not by ACTH. The recovery of activity produced by TSH administration was inhibited by cycloheximide. Hypophysectomy, or TSH and cycloheximide administration, did not produce any significant changes in the concentrations of calmodulin, suggesting that the alteration of these enzyme activities is not induced by a decrease in the concentration of calmodulin. Since forskolin activation of adenylate cyclase did not restore the reduced activity in the hypophysectomized rat thyroid to the level found in the sham-operated control rat thyroid, we conclude that there is a reduction of the amount of enzyme after hypophysectomy rather than a change of the active site on adenylate cyclase. The spontaneous restoration of adenylate cyclase and cyclic AMP phosphodiesterase activities after hypophysectomy implies that cyclic AMP-metabolizing enzymes are responsive to an autoregulatory mechanism in thyroid follicular cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Stimulatory effect of a traditional herbal medicine, Unkeito on LH-RH release].

In order to study the effect of Unkeito (Chinese name, Wen-Jan-Tang), a traditional Chinese herbal medicine and its components on luteinizing hormone-releasing hormone (LH-RH) and LH release, the mediobasal hypothalamus (MBH) alone or the pituitary alone or the pituitary in sequence with the MBH from normal female rats in diestrus was perifused in a sequential double-chamber perifusion system. LH-RH release from MBH increased significantly (p less than 0.05) by 50-100% of the basal level 30-90 min after the beginning of Unkeito administration. Unkeito at 5 micrograms/ml induced significant LH release (60-95% increase) from the pituitary in series with the MBH, but had no effect on LH release from the pituitary perifused alone. One of Unkeito's components Botanpi induced significant LH release, although other five components had no effect on LH release. These data suggest that Unkeito induces LH release from the pituitary through hypothalamic LH-RH, and can be used for the treatment of patients with hypothalamic amenorrhea.

Animals↗

[Circulating free T3 in pregnancy, liver diseases, diabetes mellitus and thyroid diseases].

Measurement of serum concentrations of free triiodothyronine (FT3) is considered to be an accurate index of thyroid function in the patient. In this study, we measured serum concentrations of FT3, free thyroxine (FT4) and reverse triiodothyronine (rT3) by radioimmunoassay in blood samples taken from the navel cord of 20 newborns as well as 20 nonpregnant women, 20 pregnant women, 10 patients with liver diseases, 25 patients with diabetes mellitus, 65 patients with hyperthyroidism, 30 patients with primary hypothyroidism and 29 normal subjects. In pregnant women, serum FT3 and FT4 levels gradually decreased as the pregnancy progressed. In cord blood, FT3 levels were less than a quarter of the values found during the first trimester of pregnancy or that of non-pregnant women, whereas serum rT3 levels were drastically increased. In chronic hepatitis, liver cirrhosis and diabetes mellitus, serum FT3 and FT4 levels were significantly lower than that in the controls. In thyroid diseases, serum FT3 levels varied parallel to other thyroid hormone levels. In primary hypothyroidism, however, serum FT3 levels were still lower than these in the controls after treatment with 1-thyroxine, whereas other thyroid hormone levels and TSH levels returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of pituitary transplants on the LH-RH concentrations in the medial basal hypothalamus and hypophyseal portal blood.

The effects of hyperprolactinemia on catecholamine turnover in the medial basal hypothalamus (MBH) and on the luteinizing hormone-releasing hormone (LH-RH) concentrations in MBH and hypophyseal portal blood were investigated in female Wistar rats. Chronic endogenous hyperprolactinemia was produced by implantation of anterior pituitary glands under the kidney capsule. Catecholamine turnover in the MBH was studied by inhibiting monoamine oxidase and then measuring the accumulation of catecholamines by high-performance liquid chromatography with electrochemical detection. Rats bearing pituitary transplants exhibited: (1) persistent vaginal diestrus within 3-6 days of the implantation; (2) increased serum concentrations of prolactin (PRL); (3) decreased serum concentrations of luteinizing hormone (LH); (4) increased pituitary concentrations of LH and follicle-stimulating hormone (FSH); (5) increased turnovers of dopamine in the MBH; and (6) decreased concentrations of LH-RH in the MBH and in plasma of hypophyseal portal blood. These findings suggest that chronic hyperprolactinemia may increase dopaminergic tone in the MBH that may inhibit LH-RH secretion from the MBH, and LH release from the pituitary. These processes may be responsible for disturbances of cyclic pituitary-ovarian activity.

Animals↗

Inhibitory effect of thyroid hormones on pituitary cyclic amp phosphodiesterase activity in vitro.

Thyroid hormones effectively inhibited partially purified cyclic AMP phosphodiesterase from the anterior and posterior lobes of bovine pituitary gland competitively with the substrate, but thyronine, diiodotyrosine, monoiodotyrosine, thyrotropin, thyrotropin releasing hormone, dexamethasone, and luteinizing hormone releasing hormone did not inhibit this enzyme activity. Ki values were found to be 1.0 and 2.5 microM for thyroxine, and 8.0 and 13.5 microM for triiodothyronine in the anterior and posterior lobes, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗

Replenishment of pituitary estrogen receptor in chronically estrogenized rats.

Replenishment of pituitary estrogen receptor (ER) following a single injection of estradiol-17 beta (E2) was examined in chronically estrogenized ovariectomized rats. Subcutaneous implantation of E2-pellet in castrated rats for 7 days caused a shift of ER distribution in the pituitary (39.9 +/- 5.7 fmol/10 mg tissue in the cytosol vs 24.8 +/- 1.9 fmol/10 mg tissue in the nucleus). An intraperitoneal injection of 5 micrograms E2 in the E2-implanted rats resulted in a significant decrease in cytosol ER with a concomitant significant increase in nuclear ER (16.6 +/- 1.2 fmol in the cytosol vs. 36.7 +/- 4.1 fmol in the nucleus at 1 h). However, cytosol ER was rapidly replenished, which was accompanied by nuclear ER reduction, and both values returned to the pre-injection levels at 4 h. An administration of 150 micrograms cycloheximide, that effectively blocked protein synthesis in the E2-implanted and 5 micrograms E2 injected rats, completely inhibited the replenishment of ER. These findings suggest that replenishment of ER following E2 administration in the pituitary of chronically estrogenized rats is entirely dependent on protein synthesis.

Animals↗

Divergent effects of prolactin on 4-ene-5 alpha-reductase activity and production of C19-steroids from progesterone in immature rat ovary.

Female rats of the Sprague-Dawley strain were used. Two pituitaries from 9-week old rats were grafted in both kidneys of 21-day old rat to induce hyperprolactinemia. All rats with or without pituitary isografts were hypophysectomized on day 26. Starting from day 29, the rats in groups of 8-11 were injected daily with 5 micrograms NIH-LH-S19 or saline for 3 days. Ovarian homogenates from these rats on day 32 were incubated with [14C]4-androstene-3,17-dione or [3H]progesterone and steroid metabolism was estimated. In the hypophysectomized rat ovary, the 5 alpha-reductase activity was stimulated significantly by LH. Although pituitary isograft alone had no stimulative effect on 5 alpha-reductase activity of the hypophysectomized rat ovary, concomitant treatment with LH and pituitary isograft (prolactin) had an additive effect. Formation of the sum of C19-steroids from progesterone in the hypophysectomized rat ovary was stimulated markedly by LH but reduced slightly by prolactin. The LH-induced production of C19-steroids from progesterone was inhibited markedly by prolactin. These results indicate that prolactin treatment inhibits basal and LH-induced production of C19-steroids from progesterone but stimulates LH-induced 4-ene-5 alpha-reductase activity in immature rat ovary.

Androgens↗

Specific antibodies to porcine zona pellucida detected by quantitative radioimmunoassay in both fertile and infertile women.

The specific radioimmunoassay system was developed for the titration of the antibodies to porcine zona pellucida (ZP) in human sera by using 125I-labeled purified porcine ZP as antigen, which is known to have cross-reactivity with human ZP. The antibodies in human sera were detected in 3 of 11 (27%) women with unexplained infertility, in 16 of 48 (33%) amenorrheic patients, in 4 of 12 (33%) fertile women, and in 3 of 10 (30%) men. Moreover, antibody titers in infertile women were no higher than those in fertile women and in men. These results seem to suggest that the antibodies in human sera that cross-react with porcine ZP may not be an important factor in causing infertility in women.

Animals↗

Site of negative feedback action of estrogen on gonadotropin secretion in normal women.

We have reported that iv administration of conjugated estrogens results in no significant change in the plasma LH-RH level during the negative feedback phase of LH, suggesting that estrogen does not suppress LH by decreasing hypothalamic LH-RH. To determine the site of estrogen action during the negative feedback phase, we studied the pituitary response to a small amount of LH-RH after estrogen administration in normal cyclic women in the mid-follicular phase. The pituitary responses to an iv bolus of 2.5 micrograms of synthetic LH-RH were evaluated by measuring serum LH and FSH 2 h before and 8 h after administration of 20 mg of conjugated estrogens (Premarin). The mean levels of serum LH and FSH were significantly (p less than 0.05) decreased 8 h after the injection. The peak responses of LH and FSH to LH-RH were also significantly (p less than 0.05) reduced after Premarin administration. These findings suggest that the negative feedback effect of estrogen on gonadotropin secretion is caused by its direct suppression on the pituitary response to LH-RH.

Adult↗

Impaired LH-RH release by estrogen in women with sulpiride-induced hyperprolactinemia.

The effects of hyperprolactinemia on the release of immunoreactive luteinizing hormone-releasing hormone (LH-RH) and luteinizing hormone (LH) in response to iv injection of 20 mg conjugated estrogens (Premarin) were studied. Five normal cycling women were injected with Premarin on the morning of the 7th day of the first cycle (control cycle), and then the plasma levels of LH-RH, LH, and prolactin (PRL) were determined every 8 to 16 hours for 72 h. Two months later, the same women received 200 mg of oral sulpiride daily for 8 days from the 3rd day of the cycle (sulpiride treated cycle), and then the same protocol as in the control cycle was applied. Mean (+/- SE) plasma levels of PRL on day 7 in the sulpiride treated cycle were significantly higher than those in the control cycle (118 +/- 24 ng/ml vs. 14 +/- 4 ng/ml, p less than 0.001). After estrogen injection, the mean percent increases in immunoreactive LH-RH at 32 h (control: 71 +/- 38% vs. sulpiride: 6 +/- 36%) and 40 h (154 +/- 38% vs. -5 +/- 21%) and in LH at the 48 h (175 +/- 89% vs. 57 +/- 57%) and 56 h (99 +/- 32% vs. 7 +/- 21%) were significantly (p less than 0.01 or p less than 0.05) suppressed in the sulpiride cycle. These data suggest that the impaired positive feedback effect of estrogen on LH-release in hyperprolactinemic anovulatory women may be caused, at least in part, by disturbed LH-RH release.

Adult↗