ReviewA brief history of adrenal research: Steroidogenesis – The soul of the adrenal
Highlights
► The adrenal glands were first clearly described anatomically in 1563. ► In 1856, Brown-Sequard first showed that the adrenals were essential for life. ► Organic chemistry permitted the isolation, and synthesis of many steroids. ► Identifying all the steroidogenic enzymes required molecular genetic technologies. ► Despite these advances, the adrenal cortex remains a very active area of research.
Section snippets
Introduction to the Keith Parker Memorial Lecture
It was indeed an honor to give the second Keith Parker Memorial Lecture at the biennial Adrenal Cortex Conference. Keith was a friend and a creative, ground-breaking scientist who was taken from us far too soon. We all miss him deeply. Following his discovery of the transcription factor SF1 (steroidogenic factor 1), much of Keith’s career concerned adrenal development in rodent systems, while mine has concerned human steroidogenesis, but we were both focussed on the adrenal. Below I shall
Anatomists: discovery of the adrenal
Whereas it is self-evident that the adrenal has always been with us, early anatomists apparently failed to note its presence. In the context of describing animal sacrifices, Leviticus 3:4 and 4:9 both refer to “…the two kidneys, and the fat that is on them, which is by the flanks…” (King James translation) and in a different context Claudius Galen (ca. 130–201) only described ‘loose flesh’ atop the left kidney (Leoutsakos and Leoutsakos, 2008). Thus it seems that the ancients could not
Physiologists: adrenal function
The linkage of earlier anatomy with clinical observation in the mid 19th century began the modern era of adrenal research. Thomas Addison (1793–1860) first described tuberculosis of the adrenal in 1849 (Addison, 1849) and then wrote his famous, detailed monograph “On the Constitutional and Local Effects of Disease of the Suprarenal Capsule” in 1855 (Pearce, 2004). In studies of (autopsied) patients with anemia, he found bilateral adrenal pathological changes that appeared to be independent of
Chemists: adrenal hormones
The general organic chemistry of polycyclic compounds received much attention in the early 20th century. Heinrich Wieland and Adolph Windaus received the 1927 and 1928 Nobel prizes in chemistry for their work on bile acids and the structure of cholesterol, but their structures were incorrect, featuring four-ring structures with two 5-carbon rings (Wieland, 1928, Windaus, 1928); the correct cyclopentanophenanthrene structure was then determined by Rosenheim and King in 1932 (reviewed in
Clinical investigators: adrenal hyperplasias
The effectiveness of cortisone in Addison’s disease and its increased availability quickly permitted its trial in other clinical settings. Wilkins was first to report its successful use in CAH (Wilkins et al., 1950, Wilkins et al., 1951); Bartter published similar results as an abstract (Bartter et al., 1950) and then as a full paper (Bartter et al., 1951). This opened a vigorous era of clinical investigation of the pathways of steroidogenesis in a variety of inherited adrenal and gonadal
Steroidogenic enzymes: proteins, cDNAs and genes
An understanding of steroidogenic processes required identification of the responsible steroidogenic enzymes. The discovery of cytochrome P450 enzymes was central to the understanding of steroidogenesis (for reviews and personal reflections, see Cooper, 1973, Estabrook, 2003, Omura, 2011). Early studies noted that steroid 21-hydroxylation by bovine adrenal microsomes was inhibited by carbon monoxide and reversible by light, but the responsible protein was not identified (Ryan and Engel, 1956,
Future directions
While the above tour through the adrenal cortex might suggest to the young investigator that everything of interest in the adrenal has been done, that is far from the truth. As illustrated by the outstanding science presented at the 15th Adrenal Cortex Conference, the following areas, in no particular order, require further investigation. (1) The precise molecular itinerary of a cholesterol molecule as it enters the mitochondrion and the mechanism of StAR’s action remain unclear. (2)
Acknowledgements
The author wishes to acknowledge the dozens of fellows, students and collaborators with whom he has studied steroidogenesis since the early 1980s. One, Prof. Synthia H. Mellon, deserves special mention (Fig. 7). It was reading Sindy’s 1978 Ph.D. thesis (with Seymour Lieberman, who had studied with Reichstein) that catalyzed my departure from pituitary polypeptides and into the world of steroidogenesis, and launched both a successful career and a loving marriage.
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Adrenal cortex development and related disorders leading to adrenal insufficiency
2021, Molecular and Cellular EndocrinologyCitation Excerpt :For a more comprehensive description of the specific clinical findings of all CAHs, we refer to medical textbooks, e.g. (Miller et al., 2020; Stewart and Newell-Price, 2016). The first CAH described in the medical literature and solved to the molecular genetic level was 21-hydroxylase deficiency due to autosomal recessive, pathogenic variants of the CYP21A2 gene (Miller, 2013). It is also the most frequently occurring form of CAH with a worldwide incidence of its classic form in about 1 in 10′000–15′000 newborns (Miller and Auchus, 2011; Stewart and Newell-Price, 2016).
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2020, Sperling Pediatric Endocrinology: Expert Consult - Online and PrintInterplay between estrogen-related receptors and steroidogenesis-controlling molecules in adrenals. In vivo and in vitro study
2018, Acta HistochemicaCitation Excerpt :No measurements of estradiol secretion or concentration were performed. It is worth noting here, that steroidogenesis is multi-level controlled process (Miller, 2013). It requires the coordinated expression of number of genes, proteins of various function (enzymes e.g. P450 side-chain cleavage; P450scc; transporters e.g. translocator protein; TSPO, steroidogenic acute regulatory protein; StAR; regulators and receptors), signaling molecules and their regulators in response to ACTH stimulation.
StAR protein and steroidogenic enzyme expressions in the rat Harderian gland
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