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  • Author: Iwao Nakayama x
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Katsuichiro Sudo, Iwao Yamazaki, Michio Masuoka and Ryo Nakayama

ABSTRACT

Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied.

(1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular adminstrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.

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Michio Masuoka, Tsuneo Masaki, Iwao Yamazaki, Tatsuhiko Hori and Ryo Nakayama

ABSTRACT

For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291* and its derivatives, a variety of endocrine characteristics were studied.

(1) Androgenic and anabolic activity: Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328*, to the immature orchiectomized rat resulted in significant weight increase of the levator ani** but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity: Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17β. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17β. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330*, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity: Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17β was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 μg oestrone in the adult ovariectomized rat. (4) Progestational activity: These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity: Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity: Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.

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Kenji Kashima, Shigeo Yokoyama, Tsutomu Daa, Kenji Takahashi, Iwao Nakayama and Shiro Noguchi

Kashima K, Yokoyama S, Daa T, Takahashi K, Nakayama I, Noguchi S. c-myc Expression is associated with increased proliferation activity in thyroid follicular cells of Graves' disease as stimulated by autoantibodies. Eur J Endocrinol 1996:135:69–76. ISSN 0804–4643

Expression on thyroid follicular cells of HLA-DR, c-myc protein and proliferating cell nuclear antigen (PCNA) was examined immunohistochemically in 28 cases of Graves' disease (GD) and in 29 cases of Hashimoto's thyroiditis (HT). Immunoreactivity for PCNA in GD was seen not only in follicular cells adjacent to a lymphocytic infiltration, where the follicular cells were positive for HLA-DR, but also in hyperplastic follicular cells without the infiltration. The distribution of expressed c-myc protein was similar to that of PCNA in GD but not in HT. Semiquantitatively graded degrees of lymphocytic infiltration and expression of HLA-DR, c-myc and PCNA in GD showed a high correlation with one another. However, the degrees of c-myc expression in HT showed no significant correlation with any other degrees. Intraperitoneal injection of bovine TSH or of immunoglobulins derived from a patient with GD in rabbits induced hyperplastic change of thyroid follicular cells, as reflected in PCNA and c-myc immunoreactivity, as well as strong peroxidase and acid phosphatase activity. Immunization with synthesized peptide of thyrotropin receptor also exhibited the same results in the rabbit thyroids. Our results indicate that c-myc expression on follicular cells of GD may reflect a stimulation by autoantibodies mediated through the thyrotropin receptor.

Kenji Kashima, Department of Pathology, Oita Medical University, 1-1 Oita-gun, Oita 879-55, Japan