Ahlin K, Forsberg J G, Jacobsohn D, Thore-Berger B
Arch Anat Microsc Morphol Exp. 1975 Jan-Mar;64(1):27-44.
Male and female offspring of rats given antiandrogens, the steroidal BOMT or the non steroids DIMP or Sch 13521, daily during the last third of pregnancy were studied. Detailed examinations were made of the genital tract of male, and of the nipples of male and female offspring. A) Male offspring. 1) Genital tract of newborn and 31-91 day old males : Modifications of the development of accessory sexual tissues were found in all treatment groups. As indicated by the severity of deviations from normal (morphology and weight of sex accessories), the antiandrogenic effect of the preparations, in the doses given to the mother rats, increased from BOMT (50 or 75 mg/day) via Sch 13521 (30 mg/day) and DIMP (50 or 60 mg/day) to Sch 13521 (60 mg/day). 2) Nipples of 10-60 day old males : Whole mount preparations were made unilaterally of the row of 6 mammary glands with nipples. The number of intact and abnormal nipples, respectively, was recorded. The relation between intact and abnormal nipples served as indicator of the efficiency of the antiandrogenic substances studied. The result showed that the antiandrogenic effect increased from BOMT to Sch 13521, 60 mg, in the same order as that arrived at from studies of the genital tract. The combined results obtained from the male offspring indicated that the tissues of the genital region, the growth and differentiation of which was most readily impaired by antiandrogens, were the same as those known from other work to be stimulated most easily in female rat fetuses by testosterone. B) Female offspring. Nipples of 31-60 day old females were judged from whole mount preparations and recorded as in the males. The nipples of adult virginal females were examined macroscopically. The same procedure was applied to lactating females, but the results were controlled in consecutive lactational periods and at autopsy. The 3 groups of females showed uniformly that 1) offspring of rats given BOMT during pregnancy had many (about 50 per cent) malformed nipples and 2) the treatment of mother rats with DIMP or Sch 13521 did not influence the development of nipples in female offspring. The result was assumed to be due to an androgenic effect of the steroidal antiandrogen, BOMT, on the nipple anlage.
对在孕期最后三分之一阶段每天给予抗雄激素(甾体类的BOMT或非甾体类的DIMP或Sch 13521)的大鼠的雄性和雌性后代进行了研究。对雄性后代的生殖道以及雄性和雌性后代的乳头进行了详细检查。A)雄性后代。1)新生雄性及31至91日龄雄性的生殖道:在所有治疗组中均发现附属生殖组织发育存在改变。根据与正常情况(性附属器官的形态和重量)的偏差严重程度表明,给予母鼠的制剂的抗雄激素作用,按照从BOMT(50或75毫克/天)经Sch 13521(30毫克/天)和DIMP(50或60毫克/天)到Sch 13521(60毫克/天)的顺序增强。2)10至60日龄雄性的乳头:对带有乳头的一排6个乳腺进行单侧整装制片。分别记录完整乳头和异常乳头的数量。完整乳头与异常乳头的比例作为所研究抗雄激素物质效果的指标。结果表明,抗雄激素作用从BOMT到60毫克的Sch 13521,其增强顺序与从生殖道研究得出的顺序相同。从雄性后代获得的综合结果表明,生殖道组织的生长和分化最容易受到抗雄激素的损害,这些组织与其他研究中已知的在雌性大鼠胎儿中最容易受到睾酮刺激的组织相同。B)雌性后代。对31至60日龄雌性的乳头进行整装制片评估,并如雄性那样进行记录。对成年未孕雌性的乳头进行宏观检查。对哺乳期雌性采用相同程序,但在连续哺乳期和尸检时对结果进行对照。这三组雌性均一致表明:1)孕期给予BOMT的大鼠的后代有许多(约50%)乳头畸形;2)用DIMP或Sch 13521处理母鼠对雌性后代乳头的发育没有影响。该结果被认为是由于甾体类抗雄激素BOMT对乳头原基有雄激素作用。