Ogo A, Haji M, Ohashi M, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Gerontology. 1991;37(5):262-71. doi: 10.1159/000213270.
To investigate the mechanisms of age-related decline in synthesis of adrenal androgen, we studied the contents of cortisol (F) and dehydroepiandrosterone (DHEA) and the amounts of cytochrome P450 17 alpha-hydroxylase (P450c17) mRNA and cytochrome P450 11 beta-hydroxylase (P450c11) mRNA in young (1 year old) and senescent (10-12 years old) bovine adrenal glands. We also examined effects of ACTH (10(-7) M) on the secretion of F and DHEA and on the induction of P450c17 and P450c11 mRNA expression in cultured adrenal cells from young and aged cows. The content of DHEA in adrenal glands and the secretion of DHEA in response to ACTH in cultured adrenal cells from senescent cow were lower than those from young cow, while the content and ACTH-stimulated secretion of F in senescent adrenals were of a similar level to those in young adrenals. The adrenal gland from aged cow showed a significantly lower level of P450c17 mRNA compared with young bovine adrenal. However, P450c11 mRNA was expressed in senescent adrenal glands at the same level as that in young adrenals. The induction of P450c17 mRNA by ACTH (10(-7) M for 24 h) in cultured adrenal cells from aged cow also showed a decline compared with that from young cow, although there was no difference the ACTH-induced accumulation of P450c11 mRNA in cultured adrenal cells between young and senescent cow. These results suggested that the expression of P450c17 mRNA decreased in aged bovine adrenal, which may cause the age-associated decline in biosynthesis of adrenal androgen.
为研究肾上腺雄激素合成随年龄下降的机制，我们研究了年轻（1岁）和衰老（10 - 12岁）牛肾上腺中皮质醇（F）和脱氢表雄酮（DHEA）的含量，以及细胞色素P450 17α-羟化酶（P450c17）mRNA和细胞色素P450 11β-羟化酶（P450c11）mRNA的量。我们还检测了促肾上腺皮质激素（ACTH，10⁻⁷ M）对年轻和老年奶牛培养肾上腺细胞中F和DHEA分泌以及P450c17和P450c11 mRNA表达诱导的影响。衰老奶牛肾上腺中DHEA的含量以及培养肾上腺细胞中DHEA对ACTH的反应性分泌低于年轻奶牛，而衰老肾上腺中F的含量和ACTH刺激的分泌与年轻肾上腺中的水平相似。与年轻牛肾上腺相比，老年牛肾上腺中P450c17 mRNA水平显著降低。然而，P450c11 mRNA在衰老肾上腺中的表达水平与年轻肾上腺中的相同。与年轻奶牛相比，老年奶牛培养肾上腺细胞中ACTH（10⁻⁷ M，作用24小时）诱导的P450c17 mRNA也有所下降，尽管年轻和衰老奶牛培养肾上腺细胞中ACTH诱导的P450c11 mRNA积累没有差异。这些结果表明，老年牛肾上腺中P450c17 mRNA的表达下降，这可能导致肾上腺雄激素生物合成随年龄增长而下降。
