History of Adrenal Research: From Ancient Anatomy to Contemporary Molecular Biology

Abstract

The adrenal is a small, anatomically unimposing structure that escaped scientific notice until 1564, and whose existence was doubted by many until the 18 th 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 19 th 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 1962-64, 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.

An Abbreviated History of Aldosterone Metabolism, Current and Future Challenges

“…A comprehensive history of the adrenal gland was recently published [1]. The anatomy of the human adrenal gland was first described by Bartolomeo Eustachi (1520-1574) in his book Opuscola Anatomica, published in 1564, with the first 8 plates of 47 engraved copper plates comprising anatomical illustrations by the Roman artist Pier Matteo Pini.…”

“…The physiological importance of the adrenal gland was first reported in 1855 by Thomas Addison, who described hyperpigmentation, anemia, general languor, debility, feebleness of the heart's action, and gastric irritability associated with diseased suprarenal capsules [2]. Soon thereafter, Charles-Edouard Brown-Sequard reported that adrenalectomy in dogs led to death, indicating that adrenal glands were essential for life [1]. The search for an adrenal secretion led to the isolation and crystallization of epinephrine by Takamine [3]; however, functions of the adrenal medulla and cortex were quickly recognized to be distinct, and that lipoidal extracts of the adrenal were required to sustain the life of adrenalectomized animals [4,5].…”

A Brief History of Congenital Adrenal Hyperplasia

“…We recently reviewed general adrenal history [1]; here we focus on congenital adrenal hyperplasia (CAH) and its central role in pediatric endocrine history; pediatric endocrinologists are highlighted in boldface . The adrenal was first described by Eustachio in 1564, although most anatomists were introduced to it by Casseri’s illustration in 1627 (Fig.…”

“…Early 20th century investigators thought there was only one adrenal hormone, confounding physiological studies of adrenalectomy. Epinephrine was the first adrenal hormone to be isolated, purified, and characterized chemically, in 1901 (see [1]). Adrenalectomy (in cats) resulted in hyponatremia and hyperkalemia, providing evidence for adrenal mineralocorticoids [13].…”

Glucocorticoid regulation of cancer development and progression

“…In 1938, Compound E was synthesized from the adrenal cortex of beef cattle ( 1 ). Within the next decade, adrenal cortical hormones (glucocorticoids or corticosteroids) were used to successfully treat inflammatory diseases such as rheumatoid arthritis and rheumatic fever.…”