Corbier P, Martikainen P, Pestis J, Härkönen P
Laboratoire de Physiologie, Centre d'Etudes Pharmaceutiques de Châtenay-Malabry, France.
Arch Physiol Biochem. 1995 Dec;103(6):699-714. doi: 10.3109/13813459508998139.
In the male rat, a dramatic increase in serum testosterone (T) of testicular origin occurs during the first few hours of postnatal life. This experiment sought to determine whether this increase affects the physiology of the adult rat ventral prostate. Male rats were castrated at the time of caesarean delivery performed at different precise stages between 21 days and 22 days of gestation (0h males). Newborn male rats were castrated after spontaneous delivery at 22 days of gestation at 6, 12, 24 or 48 h after birth. Some male rats were castrated at fetal stage 21 days 13-15 h and injected at the time of surgery with 1, 2.5 or 5 micrograms of testosterone propionate (TP). Control males were sham operated at fetal stage 21 days 13-15 h and castrated at 23 days postnatal. At 30 days of age, each male was given T replacement therapy through a T filled silastic capsule until the time of sacrifice at 100 days of age. Before T implantation at 30 days of age, castration at 0 h or 48 h after birth does not impair neither branching morphogenesis nor the organization of the prostatic acinus. In contrast, the histological structure of the ventral prostate of the 0 h males implanted with T from puberty on is greatly disturbed. Cribriform and severe atypic hyperplastic acini with various epithelial cell arrangements are common. The alveolar sheath of the prostatic glands and the interacinar stroma are enlarged. In acini with severe intraepithelial hyperplasia, the disorganized epithelium rests over a thick basement membrane that stains strongly for laminin. In some 0 h males, epithelial cells break through the periacinar fibromuscular sheath and invade the interacinar stroma. It is as though all the categories of cells comprising the ventral prostate were not programmed in the absence of neonatal androgens. The secretory activity and the expression of Prostate Binding Protein (PBP) are impaired in the ventral prostate of the 0 h males. Castration performed after 12 h after birth has no deleterious effect on either secretory activity or PBP expression. The critical period during which perinatal T affects the histological structure and the functional differentiation of the ventral prostate extends from fetal stage 21 days up to 1 or 2 days postnatal. A single injection of 2.5 micrograms TP, a dose which mimicks the postpartum T surge is sufficient for programming the histological structure and the functional differentiation of the adult ventral prostate.
在雄性大鼠出生后的最初几个小时内，睾丸来源的血清睾酮（T）会急剧增加。本实验旨在确定这种增加是否会影响成年大鼠腹侧前列腺的生理功能。在妊娠21天至22天之间的不同精确阶段进行剖腹产时对雄性大鼠进行阉割（0小时雄性）。新生雄性大鼠在妊娠22天自然分娩后，于出生后6、12、24或48小时进行阉割。一些雄性大鼠在胎儿期21天13 - 15小时进行阉割，并在手术时注射1、2.5或5微克丙酸睾酮（TP）。对照雄性大鼠在胎儿期21天13 - 15小时进行假手术，并在出生后23天进行阉割。在30日龄时，每只雄性大鼠通过填充有睾酮的硅橡胶胶囊进行睾酮替代治疗，直至100日龄处死。在30日龄植入睾酮之前，出生后0小时或48小时进行阉割既不损害分支形态发生，也不损害前列腺腺泡的组织结构。相比之下，从青春期开始植入睾酮的0小时雄性大鼠腹侧前列腺的组织结构受到极大干扰。常见有筛状和严重非典型增生的腺泡，上皮细胞排列多样。前列腺腺泡的肺泡鞘和腺泡间基质增大。在有严重上皮内增生的腺泡中，紊乱的上皮细胞位于强烈染色的层粘连蛋白厚基底膜上。在一些0小时雄性大鼠中，上皮细胞突破腺泡周围纤维肌肉鞘并侵入腺泡间基质。就好像构成腹侧前列腺的所有细胞类型在没有新生儿雄激素的情况下没有被编程一样。0小时雄性大鼠腹侧前列腺的分泌活性和前列腺结合蛋白（PBP）的表达受损。出生后12小时后进行阉割对分泌活性或PBP表达均无有害影响。围产期睾酮影响腹侧前列腺组织结构和功能分化的关键时期从胎儿期21天延伸至出生后1或2天。单次注射2.5微克TP，这一模拟产后睾酮激增的剂量足以对成年腹侧前列腺的组织结构和功能分化进行编程。
