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Biomedical subjects

T Aono

Publications and source records attributed to T Aono.

At least 235 records · Page 13Linked to original sources

Effects of hyperprolactinemia on FSH- or LH-induced activities of 17 beta-oxidoreductase, 5 alpha-reductase, and 17-hydroxylase in hypophysectomized rat testes.

Two pituitaries from 7-week-old female rats (Sprague-Dawley strain) were grafted under the capsule of the left kidney of a 49-day old male rat. The pituitary grafted and sham-operated rats were hypophysectomized at 56 days of age. The hypophysectomized rats were given daily injections of NIAMDD-oFSH-13 (20 micrograms/0.5 ml saline), NIAMDD-oLH-23 (9 micrograms/0.5 ml saline) or saline for 4 days starting from day 58. The treated rats and normal male rats were killed at 61 days of age. Testicular homogenates were incubated with [14C]4-androstene-3, 17-dione or [3H] progesterone, and enzyme activities per testes were estimated. Hypophysectomy caused significant decreases in activities of testicular 17 beta-oxidoreductase and 17-hydroxylase. The decreased activity of 17 beta-oxidoreductase was significantly stimulated by FSH or LH treatment, whereas the decreased 17-hydroxylase activity was stimulated only by LH treatment. Although pituitary grafts alone showed little or no effect on these enzyme activities in the hypophysectomized rats, the grafts significantly inhibited FSH-stimulated 17 beta-oxidoreductase activity and the LH-stimulated 17 beta-oxidoreductase and 17-hydroxylase activities but enhanced LH-induced 5 alpha-reductase activity. The present results confirm previous findings that an excess of prolactin directly inhibits LH-stimulated 17-hydroxylase activity but enhances LH-induced 5 alpha-reductase activity in the rat testis. The present results also demonstrate that the same grafts directly inhibit FSH-stimulated 17 beta-oxidoreductase activity but have no effect on FSH-induced 5 alpha-reductase activity.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Absence of effect of estrogen on dopamine, norepinephrine and beta-endorphin-like immunoreactivity in human plasma.

The plasma concentrations of immunoreactive norepinephrine (NE), dopamine (DA), beta-endorphin (beta-E), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were determined by RIA and HPLC every 6 h until 72 h after iv administration of conjugated estrogens during the midfollicular phase. The LH level showed a biphasic pattern after the injection of conjugated estrogens, i.e. significant suppression (-50%) for 6-42 h after the injection, followed by a rebound increase with a peak (+85%) at 72 h. The plasma levels of immunoreactive beta-E, NE and DA did not change significantly for 72 h after the injection.

Adult↗

Substance P stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro with involvement of oestrogen.

The effects of substance P on the release of LH and GnRH were examined in a sequential double-chamber perifusion system by perfusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in dioestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats were perifused in series with substance P (10(-6) mol/l), the concentration of LH in the efflux was significantly (P less than 0.05) increased by 70-120% compared with that before the injection, but substance P had no effect on LH release from the pituitary perifused alone. This LH release by substance P increased in a dose-dependent manner and was blocked by substance P antagonist. Administration of 10(-6) mol/l substance P induced a significant release (40-80% increase, P less than 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10(-6) mol/l substance P induced significant release (50-100% increase, P less than 0.05) of LH and GnRH in ovariectomized rats with an implanted oestradiol capsule, but caused no significant increase in LH release in ovariectomized rats without an oestradiol capsule. Progesterone injection to both ovariectomized rats and ovariectomized rats with an implanted oestradiol capsule had no significant effect on the response of LH to substance P. These findings suggest that substance P induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that oestrogen may be involved in these processes.

Animals↗

[Expression of Thomsen-Friedenreich antigen (T-Ag) in gynecologic cancer tissues].

The expression of Thomsen-Friedenreich antigen (T-Ag), the precursor of MN blood group antigen, was studied by the ABC method with Arachys Hypogaea lectin (PNA) and the relationship of the results to the histology and clinical behavior of primary gynecologic cancers were examined. The results were as follows: 1. In cervical squamous cell tumors, the incidence of the expression of T-Ag in invasive cancers (52.9%, 37/70) was significantly higher (p less than 0.05) than that in intraepithelial tumors (28.6%, 8/28). No cryptic T-Ag(-) tissue was found in intraepithelial tumors or microinvasive cancers. 2. In squamous cell carcinomas of the cervix, the incidence of cryptic T-Ag(-) tissue was high (36.4%, 4/11) in tissue of the small cell non-keratinizing type, the most undifferentiated type, whereas it was not found in 5 cases of well-differentiated keratinizing carcinoma examined. 3. In stage Ib and II cervical cancers, no relationship was recognized between the expression of T-Ag in primary lesion and extension to the parametrium or the pelvic lymph nodes. 4. The incidence of T-Ag(+) tissue in adenocarcinomas of the uterine cervix (62.5%, 5/8), the endometrium (91.7%, 11/12), and the ovarian (80%, 8/10) was higher than that in squamous cell carcinoma of the uterine cervix (52.5%, 32/61). 5. In endometrial cancers, no relationship was recognized between the expression of T-Ag and hormone receptor status.

Adenocarcinoma↗

[Antitumor effect of bromocriptine on estrogen-induced rat prolactinomas: special reference to changes in secretory granules by stereological analysis].

Bromocriptine (CB) not only lowers serum prolactin (PRL) levels but also reduces tumor size of human prolactinomas. Gen et al and we have suggested that the size reduction of human prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as the reduction in number of tumor cells secondary to cell necrosis. This implies that bromocriptine has a cytosuppressive action and possibly a cytocidal action on human prolactinomas which causes reduction in cell size and cell necrosis, respectively. The mechanism of cytosuppressive action of CB has been investigated by using mostly non-neoplastic pituitary tissues of experimental animals. A decrease in exocytosis of secretory granules and a subsequent accumulation of granules within the cells are suggested to cause the reduction in serum levels of PRL in early stage of CB treatment. However we have reported that in spite of a pronounced reduction of serum PRL levels, the number of exocytosis of the granules in human prolactinomas treated with CB for 2 weeks increased to more than 4 times much as that in the untreated prolactinomas. This is a phenomenon which contradictory to the current hypothesis. The present study is intended to clarify whether the phenomenon we observed is specific for human prolactinomas or common also to the prolactinomas in experimental animals. Seventeen female SD rats were used. They were implanted subcutaneously with a pellet of 20 mg of 17 estradiol-benzoate (20% in cholesterol), and left to grow a pituitary tumor for 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recovery of reproductive function in patients with anorexia nervosa: a 10-year follow-up study.

The recoveries of reproductive function and body weight of 21 patients with anorexia nervosa were studied in a 10-yr period from the time of their first presentation. The recovery rates of both menstruation and eating behavior were 81.0%, although at the end of the study period the rate of amenorrhea (19.0%) was still higher than that (6%) in women in the general population. The change of mean body weight in patients in whom regular menstruation was restored was not significantly different from that of patients in whom amenorrhea persisted. Of the patients, 16 married after treatment and 14 of these (87.5%) became pregnant after spontaneous (11 patients) or induced (3 patients) ovulation, and 12 delivered a baby. The present study suggests that resumption of regular menstruation may not depend only upon body weight gain, and that most patients may be able to have a child after appropriate treatments.

Adult↗

Danazol binds to progesterone receptors and inhibits the growth of human endometrial cancer cells in vitro.

Based on our recent findings that danazol, an isoxazol derivative of ethinyltestosterone, has a profound growth-inhibitory effect on an established human endometrial adenocarcinoma cell line, the effects of danazol on cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in the present study. Of the 22 uterine adenocarcinomas, estrogen, progesterone, and androgen receptors were found in 12, 14, and 4 tumors, respectively. Competitive binding studies showed that danazol specifically binds to progesterone and androgen receptors but not to estrogen receptors. Of the five cancer cells from five patients succeeded in primary cell culture, a marked inhibition of cell growth was demonstrated by addition of danazol in two cancer cells having progesterone but not androgen receptors. However, danazol did not affect the growth of the remaining three cancer cells lacking progesterone receptors. These results strongly suggest that danazol has a significant growth-inhibitory effect on human endometrial adenocarcinoma cells, possibly through progesterone receptors in the cells.

Adenocarcinoma↗

Congenital goiter sustaining normal level of serum triiodothyronine.

We attempted to elucidate the deficient site of thyroid hormone biosynthesis in the thyroid gland and the mechanism of sustaining normal T3 level in sera of a patient with congenital goiter. TY, a 8-yr-old boy, first noted the onset of a diffuse goiter at the age of 2. There was no clinical evidence of hypothyroidism except for the slight impairment of intellectual development and the awkward physical activity. BMR, T3-RSU and T4 showed low values (-13%, 20.8% and 2.2 micrograms/dl), but serum T3 was normal (180 ng/dl). Serum TSH was 18 microU/ml. The intrathyroidal T3 and T4 were slightly low. Thyroidal 131I uptake was high, but KSCN discharge test was negative. Percent distribution of 131I labelled amino acids in the pancreatin digested thyroid homogenate was 17.4% in MIT, 33.4% in DIT and 11.3% in T3 and T4. Thyroid iodide peroxidase activities in mitochondrial and microsomal fractions were slightly low (19.6 and 26.8 (normal: 32 +/- 3.0 and 37.4 +/- 9.5) mumoles/mg protein). The activity was not increased by the addition of hematin. Thyroglobulin was found to be normal. A biological half life of 131I labelled T4 was shorter (3.5 days) than that of the normal. Electron microscopic examination exhibited the increment and expansion of endoplasmic reticulum in the follicular cell. Low iodide peroxidase activity of this patient may correlate to low T3 and T4 level in the thyroid cell. Moreover, shortened biological half life of T4 implies that normal T3 level in serum is sustained by the accelerated conversion of T4 to T3 in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

High activity of cyclic 3',5'-nucleotide phosphodiesterase in sera of patient with phaeochromocytoma.

Our previous observations that serum cyclic 3',5'-nucleotide phosphodiesterase activity varied in thyroid disorders and was positively correlated with thyroid function stimulated us to investigate the phosphodiesterase levels in sera of patients with pituitary and adrenal disorders, and the response to glucagon in normal subjects. Both serum cyclic AMP phosphodiesterase (cyclic AMP-PDE) and cyclic GMP phosphodiesterase (cyclic GMP-PDE) activities were measured at a low substrate concentration. Serum cyclic AMP-PDE activity was elevated in five patients with phaeochromocytoma and was not elevated in patients with Cushing's syndrome or acromegaly, compared to the level in normal subjects. Increased enzyme activities returned to normal after resection of the tumours. Intramuscular injection of glucagon to five healthy subjects elevated cyclic AMP levels and cyclic AMP-PDE activity in plasma. These results imply that the increased cyclic AMP level by the activation of cyclase may have induced cyclic AMP-PDE in the target organ and the soluble cyclic AMP-PDE may leak into blood vessels from target organs.

3',5'-Cyclic-AMP Phosphodiesterases↗

Wen-jing-tang, a traditional Chinese herbal medicine increases luteinizing hormone release in vitro.

For examination of the effect on luteinizing hormone (LH) release of Wen-Jing-Tang, a traditional Chinese herbal medicine, the pituitary from normal female rats in diestrus was perifused alone or in sequence with the mediobasal hypothalamus (MBH) in a sequential double-chamber perifusion system. Wen-Jing-Tang at 5 or 500 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. These data suggest that Wen-Jing-Tang induces LH release from the pituitary through hypothalamic LH-RH.

Animals↗

Effect of somatostatin and dopaminergic agents on bovine pituitary phosphodiesterase activity.

The effects of somatostatin and dopaminergic agents on pituitary cyclic nucleotide phosphodiesterases that had been partially purified through DEAE cellulose column chromatography were studied. Somatostatin, L-dopa, dopamine and CB-154(2-bromo-alpha-ergocriptine) competitively inhibited the pituitary cyclic AMP phosphodiesterase activity, especially that of the low Km enzyme. This inhibition was most potent in the case of somatostatin and CB-154.

3',5'-Cyclic-AMP Phosphodiesterases↗

Testicular responsiveness to long-term administration of hCG and hMG in patients with hypogonadotrophic hypogonadism.

Steroidogenic responsiveness and amelioration of sperm number and motility following long-term intramuscular hCG and hMG administration were evaluated in 18 males with hypogonadotrophic hypogonadism (HH). The patients consisted of 13 patients with isolated gonadotrophin deficiency (IGD) and 5 patients hypophysectomized at an early or middle pubertal period. Basal serum levels of testosterone and 17 beta-estradiol were within prepubertal range in all patients before the treatment. Serum testosterone levels reached the normal adult male levels within 12-24 months of the treatment in only 2 of 7 younger patients and 1 of 6 older patients with IGD, whereas in all hypophysectomized patients serum levels of both testosterone and 17 beta-estradiol increased to the levels found in normal adult males within 6 months of the treatment. The mean peak levels of serum testosterone and 17 beta-estradiol, respectively, during the treatment were 2.1 +/- 0.8 (SD) ng/ml and 10.8 +/- 4.9 (SD) pg/ml in younger patients with IGD, 1.4 +/- 0.9 ng/ml and 9.7 +/- 5.1 pg/ml in older patients with IGD and 6.0 +/- 1.2 ng/ml and 34.2 +/- 14.8 pg/ml in hypophysectomized patients. Quantitative improvement in both sperm density and sperm motility were found in 4 of 7 younger patients, 1 of 6 older patients with IGD and all hypophysectomized patients, but only 3 of hypophysectomized patients (3 of 18 patients) could become fertile.

Adolescent↗

Retinoic acid enhances cell responses to epidermal growth factor in mouse mammary gland in culture.

Addition of epidermal growth factor (EGF) at up to 100 ng/ml to the medium of cultured explants of mouse mammary gland increased thymidine incorporation into DNA dose dependently. Addition of retinoic acid alone at 10 micrograms/ml to the medium had no significant effect on DNA synthesis, but addition of EGF with retinoic acid enhanced the EGF-stimulated DNA synthesis. Furthermore, pretreatment of mammary explants with retinoic acid enhanced the effect of EGF plus retinoic acid on cell growth. EGF inhibited the synthesis of casein and decreased alpha-lactalbumin activity of mammary explants in culture in the presence of insulin, cortisol, and PRL. Retinoic acid alone had no significant effect on the synthesis of casein, but suppressed alpha-lactalbumin activity dose dependently. Concomitant addition of retinoic acid with EGF had no significant effect on EGF-induced inhibition of casein synthesis, but enhanced EGF-induced inhibition of alpha-lactalbumin activity dose dependently. Measurement of specific binding of [125I]EGF to mouse mammary glands in culture demonstrated that pretreatment of the explants with retinoic acid slightly, but significantly, enhanced the specific binding of EGF to its cellular receptors.

Animals↗

Stimulatory effect of prolactin on luteinizing hormone-induced testicular 5 alpha-reductase activity in hypophysectomized adult rats.

Two pituitaries from 7-week-old female rats were grafted under the capsule of the left kidney of 50-day-old male rat to induce hyperprolactinemia. All of the pituitary-grafted and sham-operated rats were hypophysectomized at 56 days of age. The hypophysectomized rats in groups of 4 were given daily sc injections of saline or 9 micrograms NIADDK-ovine-(o)LH-23 for 4 and 5 days starting from days 58 and 70, respectively (short and long term hypophysectomized groups). The metabolism of [3H]progesterone or [14C]androstenedione by testicular homogenates, concentrations of testosterone and 5 alpha-androgens (androsterone plus 5 alpha-androstane-3 alpha, 17 beta-diol) in the serum and testes, and testicular LH receptors were estimated. Hypophysectomy caused significant decreases in testicular enzyme activities per gram of tissue, androgen production, and testicular LH receptors. In the testes of hypophysectomized rats, LH treatment significantly stimulated 5 alpha-reductase and 17-hydroxylase activities. Although pituitary grafts alone showed little or no effect on these testicular enzyme activities, hyperprolactinemia induced by the grafts markedly enhanced the LH-stimulated 5 alpha-reductase activity in both groups, especially in the long term hypophysectomized group. Therefore, androsterone and 5 alpha-androstane-3 alpha,17 beta-diol were shown to be the major C19-steroid products (immature type of testicular androgen production) in the LH- and PRL-stimulated testes of long term hypophysectomized adult rats. On the other hand, hyperprolactinemia was associated with a significant inhibition and a slight increase of the LH-stimulated 17-hydroxylase activities in the short and long term hypophysectomized groups, respectively. This difference can be attributed to both a PRL-induced increase in testicular LH receptors and a PRL-induced inhibition of 17-hydroxylase via a postreceptor mechanism(s). The present findings demonstrate for the first time that PRL directly stimulates LH-induced 5 alpha-reductase activity in the testes. It appears that PRL may play a role in the increased production of 5 alpha-C19-steroids and the parallel decrease of testosterone production in immature rat testes.

17-Hydroxysteroid Dehydrogenases↗