Lo M J, Wang S W, Kau M M, Chen J J, Chen Y H, Fang V S, Ho L T, Wang P S
Department of Physiology, National Yang-Ming University, Taiwan, Republic of China.
J Investig Med. 1998 Dec;46(9):444-52.
We investigated the direct effects of propylthiouracil (PTU) on corticosterone secretion both in vivo and in vitro.
Male rats were divided into 4 groups and then injected subcutaneously with saline, PTU, PTU plus thyroxine (T4), or T4 once daily for 2 weeks. After 2 weeks, rats were decapitated or received adrenocorticotropic hormone (ACTH), intravenously. Zona fasciculata-reticularis (ZFR) cells from normal, saline-, PTU-, PTU plus T4-, or T4-treated rats were incubated with ACTH, forskolin, 8-Br-cAMP, deoxycorticosterone (DOC) +/- PTU (1, 2, or 5 mg/mL) at 37 degrees C for 2 hours. Corticosterone concentrations in plasma and cell media, and 3':5'-cyclic adenosine monophosphate (cAMP) production in ZFR cells were determined by radioimmunoassay. The effects of PTU on the activities of steroidogenic enzymes in ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography.
The basal and ACTH-stimulated levels of plasma corticosterone in PTU-treated rats were lower as compared to saline-treated animals. Both basal and ACTH-stimulated corticosterone secretion were inhibited by PTU > 2 mg/mL in rat ZFR cells. The cAMP production induced by forskolin was lower in PTU, PTU plus T4, or T4-treated rats than in saline-treated animals. Chronic administration of PTU or PTU plus T4 inhibited the 3 beta-hydroxysteroid dehydrogenase, 21 beta-hydroxylase, and 11 beta-hydroxylase activities. Administration of PTU (1, 2, and 5 mg/mL) suppressed the basal, ACTH, 8-Br-cAMP, forskolin, and DOC-stimulated corticosterone secretion in rat ZFR cells. Likewise, PTU > 2 mg/mL inhibited the ACTH and 8-Br-cAMP-stimulated levels of intracellular cAMP in rat ZFR cells.
These results suggest that PTU counteracts both basal and ACTH-induced adrenal steroidogenesis through their attenuation of the activity of 11 beta-hydroxylase and cAMP production in rat ZFR cells.
我们研究了丙硫氧嘧啶（PTU）在体内和体外对皮质酮分泌的直接影响。
将雄性大鼠分为4组，然后每天皮下注射生理盐水、PTU、PTU加甲状腺素（T4）或T4，持续2周。2周后，大鼠断头或静脉注射促肾上腺皮质激素（ACTH）。将来自正常、生理盐水、PTU、PTU加T4或T4处理大鼠的束状带-网状带（ZFR）细胞与ACTH、福斯可林、8-溴环磷酸腺苷（8-Br-cAMP）、脱氧皮质酮（DOC）+/-PTU（1、2或5mg/mL）在37℃孵育2小时。通过放射免疫测定法测定血浆和细胞培养基中的皮质酮浓度以及ZFR细胞中3':5'-环磷酸腺苷（cAMP）产量。通过薄层色谱法分离的中间甾体产物的量来测量PTU对ZFR细胞中甾体生成酶活性的影响。
与生理盐水处理的动物相比，PTU处理的大鼠血浆皮质酮的基础水平和ACTH刺激水平较低。在大鼠ZFR细胞中，PTU>2mg/mL可抑制基础和ACTH刺激的皮质酮分泌。福斯可林诱导的cAMP产量在PTU、PTU加T4或T4处理的大鼠中低于生理盐水处理的动物。长期给予PTU或PTU加T4可抑制3β-羟基类固醇脱氢酶、21β-羟化酶和11β-羟化酶的活性。给予PTU（1、2和5mg/mL）可抑制大鼠ZFR细胞中基础、ACTH、8-Br-cAMP、福斯可林和DOC刺激的皮质酮分泌。同样，PTU>2mg/mL可抑制大鼠ZFR细胞中ACTH和8-Br-cAMP刺激的细胞内cAMP水平。
这些结果表明，PTU通过减弱大鼠ZFR细胞中11β-羟化酶的活性和cAMP的产生，抵消基础和ACTH诱导的肾上腺类固醇生成。
