Long-Lasting Effect of Early Postnatal Treatment with Estrogen on the Hypothalamo-Hypophysio-Ovarian Axis in Female Rats

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  • 生後早期におけるエストロゲン投与の視床下部・下垂体・卵巣系へ及ぼす持続的影響
  • 生後早期におけるエストロゲン投与の視床下部・下垂体・卵巣系へ及ぼす持接的影響
  • セイゴ ソウキ ニ オケル エストロゲン トウヨ ノ シショウカブ カスイタイ

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Abstract

Successive subcutaneous injections with various doses of diethylstilbestrol (DES) was given to the female Wistar rats for different durations from the day of birth. After maturation, the two halves of each group were sacrificed at 3 and 6 months of age, respectively. The effects of early postnatal treatment with DES on the hypothalamo-hypophysio-ovarian axis were investigated. Neonatal DES treatment resulted in anovulatory conditions in all groups of the treated females. The ovarian weights of DES-treated rats were significantly smaller than those of the control females. The rats which were injected with DES 1 or 7 μg neonatally for 10 days had “sterile ovaries” containing many large vesicular follicles but not no corpora lutea. In rats treated with DES for the first 20 or 30 days of life, the ovaries were markedly atrophic and contained only small follicles with poorly developed atria. These histological findings were closely correlated with levels of the pituitary and plasma gonadotropins (FSH, LH) measured by radioimmunoassay (RIA). In either case of animals sacrificed at the age of 3 or 6 months, it was evident there was a disturbance in the secretory function of pituitary gonadotropins. Especially, in the groups receiving longterm treatment with DES, the synthesis and secretion of pituitary gonadotropins seemed to be permanently inhibited after the cessation of DES injections. On the electron microscopic examinations, small gonadotropes which were not common in the normal anterior pituitary were frequently observed in those of DES-treated animals. These small sized gonadotropes were quite similar to the atrophic gonadotropes which appeared in the pituitary transplants beneath the renal capsule. These suggest that hypophysiotrophic influence from the hypothalamus may be less active on these pituitary gonadotropes of DES-treated rats. In addition, effects of the injection period on the development of anovulatory sterility were examined. When the same total dose of DES was given, it was found that the regulatory function of gonadotropin secretion was more seriously affected in the groups receiving long-term treatment than in the groups receiving short-term treatment, based on the results of histological and electron microscopic examinations and RIA. From these points of views, a long-lasting effect of sex steroids on sexual centers in the course of the early postnatal development seems to be highly dependent on the dose and length of the injection poriod of DES.

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