The adrenal is a small, anatomically unimposing structure that escaped scientific notice until 1564 and whose existence was doubted by many until the 18th century. Adrenal functions were inferred from the adrenal insufficiency syndrome described by Addison and from the obesity and virilization that accompanied many adrenal malignancies, but early physiologists sometimes confused the roles of the cortex and medulla. Medullary epinephrine was the first hormone to be isolated (in 1901), and numerous cortical steroids were isolated between 1930 and 1949. The treatment of arthritis, Addison's disease, and congenital adrenal hyperplasia (CAH) with cortisone in the 1950s revolutionized clinical endocrinology and steroid research. Cases of CAH had been reported in the 19th century, but a defect in 21-hydroxylation in CAH was not identified until 1957. Other forms of CAH, including deficiencies of 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 17α-hydroxylase were defined hormonally in the 1960s. Cytochrome P450 enzymes were described in 1962-1964, and steroid 21-hydroxylation was the first biosynthetic activity associated with a P450. Understanding of the genetic and biochemical bases of these disorders advanced rapidly from 1984 to 2004. The cloning of genes for steroidogenic enzymes and related factors revealed many mutations causing known diseases and facilitated the discovery of new disorders. Genetics and cell biology have replaced steroid chemistry as the key disciplines for understanding and teaching steroidogenesis and its disorders.

中文翻译：

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肾上腺研究史：从古代解剖学到当代分子生物学。

肾上腺是一个解剖学上不起眼的小结构，直到 1564 年才引起科学界的注意，并且直到 18 世纪才受到许多人的怀疑。肾上腺功能是从艾迪生描述的肾上腺功能不全综合征以及伴随许多肾上腺恶性肿瘤的肥胖和男性化推断出来的，但早期的生理学家有时混淆了皮质和髓质的作用。髓质肾上腺素是第一个被分离出来的激素（1901 年），1930 年至 1949 年间分离出了许多皮质类固醇。20 世纪 50 年代用可的松治疗关节炎、艾迪生氏病和先天性肾上腺增生 (CAH) 彻底改变了临床内分泌学和类固醇研究。CAH 病例在 19 世纪已有报道，但直到 1957 年才发现 CAH 的 21-羟基化缺陷。其他形式的 CAH，包括 3β-羟基类固醇脱氢酶、11β-羟化酶和 17α-羟化酶的缺陷，是通过激素定义的在 20 世纪 60 年代。细胞色素 P450 酶于 1962-1964 年被描述，类固醇 21-羟基化是第一个与 P450 相关的生物合成活性。从 1984 年到 2004 年，对这些疾病的遗传和生化基础的了解迅速发展。类固醇生成酶和相关因子的基因克隆揭示了许多导致已知疾病的突变，并促进了新疾病的发现。遗传学和细胞生物学已取代类固醇化学，成为理解和教授类固醇生成及其疾病的关键学科。