Albrecht E D
Endocrinology. 1984 Oct;115(4):1418-25. doi: 10.1210/endo-115-4-1418.
The conversions of [3H]pregnenolone (P5) to [3H]progesterone (P4) and [3H]20 alpha-hydroxypregn-4-en-3-one (20-OHP4) were determined in vitro in ovaries of 3 (young)- and 11 (aged)-month-old rats throughout pregnancy. Aged females exhibited an increased incidence of embryonic-fetal resorption beginning at midgestation. The mean +/- SE numbers of live and dead fetuses in aged females between day 11 of gestation and term were 8.6 +/- 0.5 and 2.3 +/- 0.3, respectively, compared to 12.0 live fetuses in young females. In young animals, ovarian conversion of P5 to P4 approximated 30% on days 1-3 of gestation, increased (P less than 0.001) to a plateau of about 45% on days 6-11, then declined to 23.5% by day 15. In aged females, ovarian formation of P4 from P5 showed no significant progressive rise or fall throughout pregnancy. The increment in P4 formation observed on days 6-11 in young rats, therefore, did not occur in aged females, and the percent conversion of P5 to P4 was 40% lower (P less than 0.05 to P less than 0.005) in aged rats during this interval. Ovarian P4 formation was similarly low in aged females that did or did not exhibit embryonic death on days 9-11. From day 12 of gestation until term, the percent conversion of P5 to P4 was similar in all young and aged animals. Conversion of P5 to 20-OHP4 in young rats increased (P less than 0.005) steadily to a peak of 21.9 +/- 5.8% (mean +/- SE) at midgestation, then declined thereafter. 20-OHP4 formation was about 50% greater in aged than in young females on days 2-6, but values were similar thereafter. The mean ratio of conversion of P5 to P4 to that of P5 to 20-OHP4, therefore, was 50% lower (P less than 0.025) in aged (1.8 +/- 0.2) than in young (3.3 +/- 0.4) rats between days 6 and 11 of gestation. The subnormal amount of P4 recovered after ovarian incubation in aged females apparently reflected subnormal P4 formation and/or enhanced P4 catabolism to steroid metabolites. The present results, therefore, demonstrate intrinsic changes in ovarian function during aged rat pregnancy. The onset of fetal demise in aged females, however, does not appear to be related to this alteration in ovarian steroidogenesis.
在整个孕期，对3只（年轻）和11只（年老）月龄大鼠的卵巢进行体外实验，测定了[3H]孕烯醇酮（P5）向[3H]孕酮（P4）和[3H]20α-羟基孕-4-烯-3-酮（20-OHP4）的转化情况。年老雌性大鼠从妊娠中期开始出现胚胎-胎儿吸收的发生率增加。在妊娠第11天至足月期间，年老雌性大鼠存活和死亡胎儿的平均±标准误数量分别为8.6±0.5和2.3±0.3，而年轻雌性大鼠有12.0个存活胎儿。在年轻动物中，妊娠第1 - 3天卵巢将P5转化为P4的比例约为30%，在第6 - 11天增加（P<0.001）至约45%的平台期，然后在第15天降至23.5%。在年老雌性大鼠中，整个孕期卵巢从P5形成P4的过程没有显著的逐渐上升或下降。因此，年轻大鼠在第6 - 11天观察到的P4形成增加在年老雌性大鼠中并未出现，在此期间年老大鼠中P5向P4的转化率低40%（P<0.05至P<0.005）。在第9 - 11天出现或未出现胚胎死亡的年老雌性大鼠中，卵巢P4形成同样较低。从妊娠第12天直至足月，所有年轻和年老动物中P5向P4的转化率相似。年轻大鼠中P5向20-OHP4的转化在妊娠中期稳步增加（P<0.005）至峰值21.9±5.8%（平均±标准误），然后随后下降。在第2 - 6天，年老雌性大鼠中20-OHP4的形成比年轻雌性大鼠大约多50%，但此后数值相似。因此，在妊娠第6 - 11天期间，年老（1.8±0.2）大鼠中P5向P4的转化与P5向20-OHP4的转化的平均比值比年轻（3.3±0.4）大鼠低50%（P<0.025）。在年老雌性大鼠卵巢孵育后回收的P4量低于正常水平，这显然反映了P4形成低于正常水平和/或P4向类固醇代谢物的分解代谢增强。因此，目前的结果表明老年大鼠妊娠期间卵巢功能发生了内在变化。然而，年老雌性大鼠中胎儿死亡的开始似乎与卵巢类固醇生成的这种改变无关。
