Pepe G J, Waddell B J, Albrecht E D
Department of Physiology, Eastern Virginia Medical School, Norfolk 23501.
Endocrinology. 1989 Sep;125(3):1519-24. doi: 10.1210/endo-125-3-1519.
We have previously shown that ACTH and PRL stimulate baboon fetal adrenal dehydroepiandrosterone (DHA) production both in vitro and in vivo and that estrogen diminishes the responsivity of the adrenal to tropic peptides in vitro. In the present study we determined the effects of increasing placental estrogen production by the administration of androstenedione at midgestation on DHA production by the baboon fetus in vivo. Pregnant baboons were untreated (n = 8) or treated (n = 9) with increasing numbers of androstenedione implants inserted in the mother at 8-day intervals between days 70-100 of gestation (term = day 184). On day 100, the fetuses were exteriorized, and a constant infusion of saline (0.1 ml/min) was initiated via a catheter inserted into a femoral vein of the fetus. At 40 min, a bolus injection of either 30 nmol ACTH or 40 nmol ovine PRL was administered to fetuses. ACTH or PRL (0.2 nmol/min.0.1 ml saline) were then infused for an additional 25 min. The concentrations of serum estradiol (E2) in the uterine vein (20.2 +/- 1.5 ng/ml; mean +/- SE) and estrone (E1) in umbilical vein (11.9 +/- 3.1 ng/ml) of androstenedione-treated baboons were 2-fold greater (P less than 0.05) than respective values in untreated baboons. Baseline concentrations of DHA in the femoral vein of the fetus were similar in all treatment groups (overall mean, 120 +/- 20 ng/ml) and greater (P less than 0.05) than values (27 +/- 3) in the mother. In untreated control baboons, basal DHA concentrations in the fetus were increased (P less than 0.05) by 69 +/- 17% and 94 +/- 29% after fetal injection of ACTH (n = 4) or PRL (n = 4), respectively. In contrast, neither PRL (n = 5) nor ACTH (n = 4) had any effect on serum DHA when injected into androstenedione-treated baboons. Regardless of treatment, injection of ACTH or PRL into the fetus had no effect on DHA concentrations in the mother. Collectively, these findings indicate that the ability of the fetal adrenal to increase DHA production in response to an acute infusion of ACTH or PRL was abolished in baboons in which placental estrogen production was increased prematurely at midgestation. Therefore, we suggest that during the second half of gestation in the baboon a regulatory system may exist in utero, in which there is feedback control of the placental product estrogen on the formation of the fetal adrenal precursor DHA.
我们之前已经表明，促肾上腺皮质激素（ACTH）和催乳素（PRL）在体外和体内均可刺激狒狒胎儿肾上腺脱氢表雄酮（DHA）的产生，并且雌激素在体外会降低肾上腺对促性腺肽的反应性。在本研究中，我们通过在妊娠中期给予雄烯二酮来增加胎盘雌激素的产生，从而确定其对狒狒胎儿体内DHA产生的影响。妊娠狒狒未接受治疗（n = 8）或在妊娠70 - 100天（足月为第184天）期间每隔8天在母体中植入数量逐渐增加的雄烯二酮进行治疗（n = 9）。在第100天，将胎儿取出，通过插入胎儿股静脉的导管开始持续输注生理盐水（0.1 ml/分钟）。40分钟时，向胎儿推注30 nmol ACTH或40 nmol绵羊PRL。然后以0.2 nmol/分钟.0.1 ml生理盐水的速度继续输注ACTH或PRL 25分钟。接受雄烯二酮治疗的狒狒子宫静脉中血清雌二醇（E2）浓度（20.2±1.5 ng/ml；平均值±标准误）和脐静脉中雌酮（E1）浓度（11.9±3.1 ng/ml）比未治疗的狒狒相应值高2倍（P < 0.05）。所有治疗组胎儿股静脉中DHA的基线浓度相似（总体平均值，120±20 ng/ml），且高于母体中的值（27±3）（P < 0.05）。在未治疗的对照狒狒中，胎儿注射ACTH（n = 4）或PRL（n = 4）后，胎儿基础DHA浓度分别增加了69±17%和94±29%（P < 0.05）。相比之下，注射到接受雄烯二酮治疗的狒狒体内的PRL（n = 5）或ACTH（n = 4）对血清DHA均无任何影响。无论治疗情况如何，向胎儿注射ACTH或PRL对母体中DHA浓度均无影响。总体而言，这些发现表明，在妊娠中期胎盘雌激素产生过早增加的狒狒中，胎儿肾上腺对急性输注ACTH或PRL增加DHA产生的能力被消除。因此，我们认为在狒狒妊娠后半期，子宫内可能存在一种调节系统，其中胎盘产物雌激素对胎儿肾上腺前体DHA的形成存在反馈控制。
