Permanent Effect of Hormones and Their Related Compounds on Target Organs

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Permanent effects of hormones and their related compounds on gonadーaccessory and neoplastic tissues were studied.1. Tamoxifen. (1) Tamoxifen given neonatally induced degeneration of uterine glands, myometrium and oocytes in females, and (2) suppression of fibrocartilage formation in penis and suppression of spermatogenesis in males. (3) Critical periods of induction by tamoxifen of abnormalities in female and male mice were 7 and 3 days after birth, respectively. (4) Tamoxifen directly suppressed the ossification of pelvis in vitro.2. Sexual dimorphism of pelvis. (1) Sexual dimorphism in pelvis was formed by 30 days of age. Pubis in females is longer and thinner than the males. Ischium in males is wider and larger than the females. (2) Studies on pelvis of Tfm mouse and sequential gonadectomy revealed that shapes of pubis and ischium were controlled by estrogen and androgen, respectively.3. Polyovular follicles. (1) Polyovular follicles induced by neonatal treatment with diethylstilbestol (DES) can be ovulated by gonadotropins and (2) ova from polyovular follicles can be fertilized in vitro, though the fertilization rate is lower than those of ova from uniovular follicles from controls and neonatally DES-exposed mice.4. Tumor and blood glucose. (1) Mice developed mammary tumor showed higher blood glucose and insulin than mice without the tumor. There is a positive correlation between mammary tumor size and blood glucose. In these mice, liver was larger than the controls. (2) Mice transplanted Lewis lung carcinoma showed higher blood glucose.5. Protein profiles in irreversibly changed vagina. Two dimensional electrophoresis reveled that similar proteins were expressed both in vagina of ovariectomized mice treated neonatally with DES and in ovariectomized adult mice given injections of DES just before sacrifice. These results indicate that some proteins were permanently expressed in DES-exposed vagina.