Turocy J F, Chiang A N, Seeley D H, Eagon P K
Endocrinology. 1985 Nov;117(5):1953-61. doi: 10.1210/endo-117-5-1953.
Many of the sex-differentiated functions of the liver of adult male rats depend upon the occurrence of neonatal androgen imprinting, a brief surge of androgen early in life. We investigated whether androgen imprinting is necessary for the development and maintenance of levels of a microsomal enzyme, estrogen-2-hydroxylase (E-20Hase), and a male-specific cytosolic estrogen binder (MEB) which are higher in adult male than in adult female rats. Cimetidine, a weakly antiandrogenic H2 blocker, was administered to pregnant and lactating rats from day 12 of gestation through weaning on day 21. Livers of male progeny, 120-150 days of age, were assayed for E-2OHase and MEB activity; a maternal dose equivalent to 2.5 times the usual human dose inhibited MEB activity in the levels of the offspring by 40% but had no effect on E-2OHase. However, a higher dose (5 times the human dose) was effective in reducing the E-2OHase activity by 50%. Rats whose mothers had received either no drug or an equivalent dose of ranitidine, another H2 blocker without antiandrogenic activity, were used as controls. The groups were not different in hepatic cytosolic androgen receptor content, body weight, or serum testosterone. In other studies, the requirement of neonatal androgen imprinting for full expression of adult levels of MEB and E-2OHase was determined. Female rats, which have low levels of E-2OHase and undetectable levels of MEB, were given androgen on day 1, on day 60 after ovariectomy, or at both times. Levels of E-2OHase equivalent to those in adult males were induced in females receiving both androgen treatments, whereas either treatment alone induced E-2OHase to the level of that in males castrated at adulthood or neonatally, which is about 50% that in normal male controls. In addition, MEB levels were induced in females to 85% of that in normal males by both androgen treatments and to 50% by administration of androgen to adult females or to adult males castrated neonatally. Administration of androgen to females during the neonatal period only did not induce MEB. We conclude that both MEB and E-2OHase require androgen imprinting for full expression in adult male rats.
成年雄性大鼠肝脏的许多性别分化功能取决于新生儿雄激素印记，即在生命早期出现的雄激素短暂激增。我们研究了雄激素印记对于微粒体酶雌激素 - 2 - 羟化酶（E - 20Hase）和雄性特异性胞质雌激素结合蛋白（MEB）水平的发育和维持是否必要，成年雄性大鼠中这两种物质的水平高于成年雌性大鼠。从妊娠第12天到第21天断奶期间，给怀孕和哺乳期的大鼠注射西咪替丁，一种弱抗雄激素的H2阻滞剂。对120 - 150日龄雄性后代的肝脏进行E - 2OHase和MEB活性检测；相当于人类常用剂量2.5倍的母体剂量使后代中MEB活性水平降低了40%，但对E - 2OHase没有影响。然而，更高剂量（人类剂量的5倍）可有效降低E - 2OHase活性50%。将母亲未接受任何药物或接受等量雷尼替丁（另一种无抗雄激素活性的H2阻滞剂）的大鼠作为对照。这些组在肝脏胞质雄激素受体含量、体重或血清睾酮方面没有差异。在其他研究中，确定了新生儿雄激素印记对于成年水平的MEB和E - 2OHase充分表达的必要性。在出生第1天、卵巢切除术后第60天或两个时间点都给E - 2OHase水平低且MEB水平检测不到的雌性大鼠注射雄激素。接受两种雄激素处理的雌性大鼠诱导出了与成年雄性相当的E - 2OHase水平，而单独任何一种处理都将E - 2OHase诱导到成年后或新生期阉割雄性大鼠的水平，约为正常雄性对照的50%。此外，两种雄激素处理使雌性大鼠的MEB水平诱导到正常雄性的85%，给成年雌性或新生期阉割的成年雄性大鼠注射雄激素使MEB水平诱导到50%。仅在新生儿期给雌性大鼠注射雄激素不会诱导MEB。我们得出结论，在成年雄性大鼠中，MEB和E - 2OHase的充分表达都需要雄激素印记。
