Berman E, Laskey J W
U. S. Environmental Protection Agency Health Effects Research Laboratory, Developmental Toxicology Division, Research Triangle Park, North Carolina 27711.
Reprod Toxicol. 1993 Jul-Aug;7(4):349-58. doi: 10.1016/0890-6238(93)90024-2.
Cultures of minced, whole-ovary (whole-ovary culture) were used to determine if three selected chemicals altered steroidogenic profiles. First, phenolsulfonthalein (PST), when used in culture medium, was tested for its influence on in vitro steroidogenesis. Next, aminoglutethimide (AGTP; 0 or 150 mg/kg once) and di(2-ethylhexyl)phthalate (DEHP; 0 or 1500 mg/kg/day for 10 days) were administered in vivo to young adult cycling rats, and the ovaries and adrenals were removed and cultured for 1 h. Ovarian steroidogenic profiles of progesterone (P), testosterone (T), and estradiol (E) release into the medium were measured using radioimmunoassay techniques. PST in medium significantly decreased ovarian P production and altered T and E production so that the T/E ratio was significantly altered. Therefore, PST was excluded in the later studies. DEHP altered steroid profiles so that proestrus appeared to be delayed. AGTP decreased P and E production significantly, and T production was increased slightly in proestrus ovaries. These AGTP alterations in T and E resulted in a highly significant increase in the T/E ratio. Adrenals from the DEHP and AGTP experiments were also cultured for 1 h, and P was assayed in the medium. AGTP, but not DEHP, significantly increased the production of P in adrenals. Whole-ovary culture is recommended as an in vitro test for chemicals suspected of interfering with steroidogenesis in vivo. This test model should be placed strategically between in vivo studies of reproductive toxicity and complex in vitro mechanistic studies.
采用切碎的全卵巢培养物（全卵巢培养）来确定三种选定的化学物质是否会改变类固醇生成谱。首先，检测了培养基中使用的酚红（PST）对体外类固醇生成的影响。接下来，对成年未孕的年轻大鼠进行体内给药，分别给予氨鲁米特（AGTP；0或150mg/kg，单次给药）和邻苯二甲酸二（2-乙基己基）酯（DEHP；0或1500mg/kg/天，连续给药10天），然后取出卵巢和肾上腺并培养1小时。使用放射免疫测定技术测量培养基中孕酮（P）、睾酮（T）和雌二醇（E）的卵巢类固醇生成谱。培养基中的PST显著降低了卵巢P的产生，并改变了T和E的产生，从而使T/E比值显著改变。因此，在后续研究中排除了PST。DEHP改变了类固醇谱，使得动情前期似乎延迟。AGTP显著降低了P和E的产生，并且在动情前期卵巢中T的产生略有增加。AGTP对T和E的这些改变导致T/E比值显著升高。DEHP和AGTP实验中的肾上腺也培养了1小时，并测定了培养基中的P。AGTP显著增加了肾上腺中P的产生，但DEHP没有。推荐将全卵巢培养作为一种体外试验，用于检测怀疑在体内干扰类固醇生成的化学物质。该试验模型应战略性地置于生殖毒性的体内研究和复杂的体外机制研究之间。
