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

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 3ß-hydroxysteroid dehydrogenase, 11ß-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.

Diseases and environmental contaminants in seals from the Baltic and the Swedish west coast.

Investigations have shown that Baltic grey seal (Halichoerus grypus) and ringed seal (Phoca hispida) suffer from a disease complex described as a primary lesion in the adrenals causing secondary reactions in various other organs. Studies on historical Baltic grey seal skull bone material show that the prevalence of affected animals started to increase after World War II. The disease complex explains the dramatic decrease in the Baltic grey and ringed seal population during the 1960s and 1970s and is believed to be caused by environmental pollutants. In 1988, about 60% of the harbor seal population (Phoca vitulina) along the Swedish west coast and in the southwestern part of the Baltic died in the PDV epizootic (Phocine Distemper Virus). Whether the course of the epizootic was altered by environmental pollutants is still an open question. Studies on historical harbor seal skull bone material from both the Baltic and the Swedish west coast show that the incidence of skull bone lesions has also increased in these populations since World War II, indicating the presence of unnatural stress factors. After the epizootic, the harbor seal populations both in the Baltic and along the Swedish west coast have increased in number. Chemical analysis of tissues has been performed on the three seal species collected in various areas of the Baltic and the Swedish west coast. The concentrations of 17 metals and non-metal elements, sDDT and PCBs, DDE and PCB methylsulfones, toxaphene, chlordanes, polybrominated diphenyl ethers, PCDDs and PCDFs have been determined in selected groups of seals in order to determine spatial, species and age variations in concentrations. Furthermore, healthy animals have been compared to diseased animals. Spatial variation was found mostly within the group of organohalogenated compounds, a group of contaminants where a strong covariation between the various compounds was also found. On the basis of the analytical results as well as the pathological findings on Baltic seals, the group of DDE and PCB methyl sulfones is tentatively suggested to be more important in explaining the disease complex than coplanar structures including dioxins.