PES Trivia, at Your Fingertips
These tidbits were originally published in our 2018 President’s newsletters.
May 2018 – submitted by Walter Miller
Treating CAH with cortisone
Lawson Wilkins had ameliorated salt loss in CAH with deoxycorticosterone, but his treatments with ACTH, testosterone and several androgen analogues failed. Wilkins’ preliminary report described suppressing one patient’s urinary 17KS with cortisone (Bull Johns Hopkins Hosp 86:249, 1950). Frederic Bartter’s contemporaneous abstract on treating CAH with cortisone concludes: “These findings suggest that the adrenogenital syndrome results, not from an abnormal pituitary stimulation of the adrenal, but from an abnormal adrenal response to a normal pituitary” (JCI 29:797,1950). They simultaneously published full papers; citing each other’s work (JCEM 11:1,1951;JCI 30:237,1951). Wilkins tried many steroids, eventually cortisone, whereas Bartter’s work was based on an early understanding of the pituitary-adrenal axis; they deserve equal credit for cortisone treatment, but Bartter understood the physiology.
April 2018 – submitted by Walter Miller
Two types of hypothalamic-pituitary connection
Stephen W. Ranson established that ADH was made in hypothalamic supraoptic nuclei, that the posterior pituitary (PP) was innervated by a supraoptico-hypophyseal tract; and that disruption of this innervation caused DI, thus establishing that the PP was under neural control (Bull NY Acad Med 13:241, 1937). Lieutaud reported circulation between brain and pituitary in 1742; Wislocki & King showed that blood flowed from hypothalamus to pituitary (Am J Anat 58:421, 1936). Geoffrey Harris noted the paucity of anterior pituitary innervation and that the hypophyseal portal system regenerated following stalk section but that nerve fibers from hypothalamus to PP did not, concluding that the PP was under neural control whereas the anterior pituitary was under humoral control (Physiological Rev 28: 139,1948).
March 2018 – submitted by Walter Miller
Philip E. Smith: The pituitary controls other glands
Smith established the central role of the pituitary. He showed that the pituitary controlled frog skin pigmentation (Science 44:280, 1916), the first evidence for melanocyte-stimulating hormone. He devised a pharyngeal hypophysectomy procedure in rats sparing the pars tuberalis and hypothalamus: the animals stopped growing; the liver, spleen and kidneys got smaller; pre-pubertal animals remained pre-pubertal; and the adrenals, thyroid and gonads atrophied (JAMA 88:158, 1927; Am J Anat 45:205, 1930). Pituitary transplants or injections of pituitary homogenates largely reversed these effects. Rats hypophysectomized by a temporal approach had a similar outcome but also became markedly obese. Smith correctly concluded that this was due to an injury of the hypothalamus, thus helping to establish the hypothalamic-pituitary axis.
February 2018 – submitted by Alan Rogol
Secretin: the defining moment for endocrinology
Claude Bernard coined the term “internal secretions” to describe the release of glucose from liver glycogen (Comptes Rendus 1853; 40:589). Starling and Bayliss investigated the innervation and movement of the small bowel, for Pavlov (The Physiology of Digestion, 1904) believed that exocrine pancreatic secretion was controlled by the vagus nerve. They dissected the nerves supplying the pancreas and duodenum in dogs. Acid added to the duodenum led to pancreatic enzyme secretion. They mixed duodenal scrapings with acid and administered the supernatant iv to a dog. Within seconds pancreatic enzyme secretion occurred. Their conclusion: a precursor, “pro-secretin” released secretin with acid (J Physiol (1902; 28:325). They called it a ‘hormone’ –Gr. “I arouse to act”.
January 2018 – submitted by Walter Miller
JB Collip and the isolation of pituitary hormones
In 1933, James Bertram Collip, who had devised the insulin purification procedure that netted the Nobel Prize for Banting & MacLeod, prepared several anterior pituitary hormone fractions of varying purity (Lancet 222(5727): 1208-1209, 1933). As the pituitary extract was concentrated, the first material to precipitate was termed ‘Q extract’. Assaying fractions in the hypophysectomized rat model described by Philip E. Smith (Am J Anat 45:205-273, 1930), he showed that ‘Q extract’ was a powerful growth hormone free of gonadotropic, thyrotropic or adrenotropic activities. Once the Q extract was recovered, he removed prolactin by iso-electric precipitation, then prepared TSH by salt precipitation and fractionation with alcohol/acetone. ACTH was then precipitated at pH 5 in 75% acetone (Lancet 222(5237); 347-348, 1933).