A Century After the Description of "Hormones", Our Golden Jubilee Celebration Goes on with What is New in Endocrine Oncology: And a Lot is New!

About 3000 thousand years ago Marcus Aurelius said: "Time is a sort of river of passing events, and strong is its current; no sooner is a thing brought to sight than it is swept by and another takes its place, and this too will be swept away…" 1.

Acne pathogenesis: history of concepts.

From the first reliable descriptions of acne in the early 19th century, dermatologists recognized it as a disease of the pilosebaceous follicle. Until the middle of the 20th century, they hypothesized that seborrhoea, follicular keratosis and microorganisms could be individually responsible for the acne lesions. Inflammation was only regarded as the final and inescapable step of the acne process. Although the importance of these factors has been reevaluated, recent works still regarded them as mandatory. In the 1970s, the onset of isotretinoin dramatically improved acne management. It also provided great opportunities for a better understanding of the pathogenic factors of acne. This study analyzes their genesis and development from the seminal contributions until recent advances.

The demand for pregnancy testing: the Aschheim-Zondek reaction, diagnostic versatility, and laboratory services in 1930s Britain.

The Aschheim-Zondek reaction is generally regarded as the first reliable hormone test for pregnancy and as a major product of the 'heroic age' of reproductive endocrinology. Invented in Berlin in the late 1920s, by the mid 1930s a diagnostic laboratory in Edinburgh was performing thousands of tests every year for doctors around Britain. In her classic history of antenatal care, sociologist Ann Oakley claimed that the Aschheim-Zondek test launched a 'modern era' of obstetric knowledge, which asserted its superiority over that of pregnant women. This article reconsiders Oakley's claim by examining how pregnancy testing worked in practice. It explains the British adoption of the test in terms less of the medicalisation of pregnancy than of clinicians' increasing general reliance on laboratory services for differential diagnosis. Crucially, the Aschheim-Zondek reaction was a test not directly for the fetus, but for placental tissue. It was used, less as a yes-or-no test for ordinary pregnancy, than as a versatile diagnostic tool for the early detection of malignant tumours and hormonal deficiencies believed to cause miscarriage. This test was as much a product of oncology and the little-explored world of laboratory services as of reproductive medicine.

Evolution of the diffuse neuroendocrine system--clear cells and cloudy origins.

As early as the 2nd century, Galen proposed that 'vital spirits' in the blood regulated human bodily functions. However, the concept of hormonal activity required a further 18 centuries to develop and relied upon the identification of 'ductless glands', Schwann's cell and the recognition by Bayliss and Starling of chemical messengers. Bernard's introduction of 'internal secretion' and its role in homeostasis laid a physiological basis for the development of endocrinology. Kocher and Addison recognized the consequences of ablation of glands by disease or surgery and identified their necessary role in life. Detailed descriptions of the endocrine cells of the gut and pancreas and their putative function were provided by Heidenhain, Langerhans, Laguesse and Sharpey-Schafer. Despite the dominant 19th century concept of nervism (Pavlov), in 1902, Starling and Bayliss using Hardy's term 'hormonos' described secretin and in so doing, established the gut as an endocrine organ. Thus, nervism was supplanted by hormonal regulation of function and thereafter numerous bioactive gut peptides and amines were identified. At virtually the same time (1892), Ramón y Cajal of Madrid reported the existence of a group of specialized intestinal cells that he referred to as 'interstitial cells'. Cajal postulated that they might function as an interface between the neural system and the smooth muscles of the gut. Some 22 years later, Keith suggested that their function might be analogous to the electroconductive system of the heart and proposed their role as components of an intestinal pacemaker system. This prescient hypothesis was subsequently confirmed in 1982 by Thuneberg and a decade later Maede identified c-Kit as a critical molecular regulator in the development and function of the interstitial cells of Cajal and further confirmed the commonality of neural and endocrine cells. The additional characterization of the endocrine regulatory system of the GI tract was implemented when Feyrter (1938) using Masson's staining techniques, identified 'helle Zellen' within the pancreatic ductal system and the intestinal epithelium and proposed the concept of a diffuse neuroendocrine system. Pearse subsequently grouped the various cells belonging to that system under the rubric of a unifying APUD series. Currently, the gut neuroendocrine system is viewed as a syncytium of neural and endocrine cells sharing a common cell lineage whose phenotypic regulation is as yet unclear. Their key role in the regulation of gastrointestinal function is, however, indubitable.

El centenario de las hormonas: Un recuerdo de Ernest H. Starling y William M. Bayliss / On the centennial of hormones: A tribute to Ernest H. Starling and William M. Bayliss

En junio de 2005 se cumplió el primer centenario de la introducción de la palabra hormona para definir al mensajero químico que originado en un tejido viaja a través de la circulación para alcanzar otro tejido distante y ejercer un efecto específico. Ernest H. Starling presentó en junio de 1905 las Conferencias Croone en las que desarrolló la teoría del control químico del organismo como una culminación de sus previas investigaciones que había realizado en colaboración con el fisiólogo William M. Bayliss sobre la fisiología del corazón, el intercambio capilar, la reabsorción tubular del glomérulo renal y el peristaltismo intestinal. La primera hormona recibió el nombre de secretina y su descubrimiento desencadenó un incontable número de investigaciones multidisciplinarías que han permitido el avance en el conocimiento de la biología molecular y particularmente en el área de la endocrinología.

Ernest H. Starling introduced the term hormone 100 years ago in his Croonian Lectures to the Royal College of Physicians in June 1905. It was demonstrated for the first time that one part of the body could influence the function of another distant part. Starling for the first time suggested the word hormone. This review attempts to trace the development of studies in endocrinology, beginning in the middle of the nineteenth century. Starling discovered secretin, the first hormone, in collaboration with William M. Bayliss, and they introduced the hormone concept with recognition of chemical regulation. Thus the name hormone sparked multidisciplinary research in endocrinology and molecular biology, which shed light on the chemical communication within the organism.

Hormones, mammary growth, and lactation: a 41-year perspective.

When I was a beginning graduate student 41 yr ago it had been established that estrogen caused mammary duct growth; a combination of estrogen and progesterone was required for lobule-alveolar development of the mammary glands; and prolactin and growth hormone were essential for mammary growth. In laboratory species exogenous prolactin, glucocorticoids, and estrogen would initiate secretion of milk provided the mammary glands had a well-developed lobule-alveolar system. It was not known with certainty that progesterone inhibited the process. For some species, prolactin and thyroxine had been shown to stimulate lactation, while glucocorticoids suppressed lactation. Definitive roles for growth hormone and insulin during lactation had not been established. Studies of hormonal control of mammary growth and function in cattle were few. In vitro methods to study hormonal regulation of the mammary glands were in their infancy. Quantitative measures of changes in mammary cell numbers and specific components of milk in response to hormones were rare. The concepts for quantification of hormone concentrations, hormone receptors, growth factors, and binding proteins in blood; hormonal regulation of nutrient partitioning; and hormonally induced mechanisms of action within mammary cells were waiting to be discovered. And eventually they were. However, lest we become too enamored with our current understanding of the hormones that control mammary growth and lactation, it remains a fact that the greatest physiological stimulus for milk yield is pregnancy, not some cocktail of exogenous hormones, growth factors, receptor agonists/antagonists, or gene therapies. Viva la mom!

Forty years of cytochrome P450.

The term "cytochrome P450" first appeared in literature in 1962. It was a microsomal membrane-bound hemoprotein without known physiological functions at that time and was characterized by a unique 450-nm optical absorption peak of its carbon monoxide-bound form, which was originally reported as the spectrum of a novel "microsomal carbon monoxide-binding pigment" in 1958. Elucidation of its function as the oxygenase in 1963 triggered a rapid expansion of research on this hemoprotein. Annual numbers of the published papers dealing with cytochrome P450, which were listed in Biological Abstracts, increased from 60 in 1970 to 500 in 1980, 900 in 1990, and 1500 in 1997. Cytochrome P450 is now regarded as the collective name of a large family of hemoproteins, "cytochrome P450 superfamily, "which seems to have diversified from a single ancestral protein to many forms during the course of biological evolution and is distributed widely among various forms of life from animals and plants to fungi and bacteria. Multicellular eukaryotic organisms including animals and plants have about 100 or more P450 genes in their genomes, and those many P450 genes are expressed tissue specifically and developmental stage specifically, indicating their diverse physiological functions. In mammals, various P450s participate in the biosynthesis and metabolism of sterols and steroid hormones and the metabolism of various lipid biofactors including eicosanoids, vitamin D3, and retinoids. Oxidative metabolism of foreign hydrophobic compounds as the first step of their excretion from the animal body is apparently another major function of cytochrome P450, which protects animals from noxious foreign compounds, man-created and natural.

The emergence of endocrinology.

Endocrinology was recognized as a new branch of biological science mainly as a result of events which took place between about 1890 and 1905, but ideas and discoveries dating from antiquity contributed to it also. Experiments supporting the concept of internal secretions by the testicles were described by Aristotle (4th c. B.C.) and by Hunter (18th c.) and Berthold (19th c.). In 1855 Bernard described glucose as an internal secretion of the liver and Addison reported the effects of adrenal disease in man. Adrenalectomy was fatal in animals. Goitre was known in antiquity and cretinism had been described by Paracelsus. Myxoedema was reported by Gull in 1873, and Kocher described cachexia strumipriva in 1883. In 1888 cretinism, myxoedema and cachexia strumipriva were attributed to thyroid insufficiency. In the 1890s Gley found that tetany after thyroidectomy was due to removal of the parathyroids. In 1884 Rehn proposed that toxic goitre was due to thyroid excess. In 1889 Brown-Séquard claimed that injections of testicular extract rejuvenated the elderly, and in 1893 he introduced organotherapy. In 1891 Murray treated myxoedema successfully with thyroid extract. In 1893 Oliver and Schäfer found that an adrenal extract raised the blood pressure, and soon adrenaline was extracted from the adrenal medulla. Adrenocortical deficiency was proposed as the cause of Addison's disease, and in 1896 Osler prepared an extract which relieved one patient. Diabetes mellitus, described in the first century, was usually fatal. Thirst and polyuria followed experimental pancreatectomy, and pancreatic lesions were found in some human diabetics. In the 19th century workers in France and Germany found that diabetes resulted from absence of an internal secretion by the islets of Langerhans and, in 1893, Laguesse described the function of the islets as "endocrine". In 1895 Beatson treated advanced breast cancer successfully by oöphorectomy. In 1895 Schäfer commended study of the internal secretions to physiologists. In 1902 Bayliss and Starling discovered secretin, a chemical messenger secreted by the intestinal mucosa. In 1905 Starling proposed the name "hormone" for this class of internal secretions. By then endocrinology had been launched as a new branch of science. The crucial events which led to the recognition of endocrinology as a new branch of biological science took place between about 1890 and 1905. Many ideas and discoveries dating from antiquity and apparently unrelated at first had, however, contributed to it. Most of the organs and tissues that form the endocrine system were recognized over 100 years ago.(ABSTRACT TRUNCATED AT 400 WORDS)