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Am J Physiol Endocrinol Metab 287: E813-E814, 2004; doi:10.1152/classicessays.00022.2004 Free Article
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EDITORIAL FOCUS

ESSAYS ON APS CLASSIC PAPERS

Anterior pituitary hormones: development of a bioassay leading to the discovery of prolactin

M. Susan Smith

Division of Neuroscience, Oregon National Primate Research Center, Department of Physiology and Pharmacology, Oregon Health and Science University, Beaverton, Oregon 97006

ABSTRACT

This essay looks at the historical significance of an APS classic paper that is freely available online:

Riddle O, Bates RW, and Dykshorn SW. The preparation, identification and assay of prolactin–a hormone of the anterior pituitary. Am J Physiol 105: 191—216, 1933 (http://ajplegacy.physiology.org/cgi/reprint/105/1/191).

TODAY, WE TAKE FOR GRANTED our knowledge about the six anterior pituitary hormones, their structure, function, and assays for measurement, and their central place in the regulation of critical body functions. However, younger generations of scientists may not understand the impact that their discovery and isolation had on the scientific community. In the 1920s, almost nothing was known about the anterior pituitary. Physiologists had made extracts of the anterior pituitary and knew there were substances contained in these extracts that had powerful effects to stimulate reproductive organs, growth, the adrenal and thyroid glands, and milk secretion by the mammary gland. At that time, very limited techniques were available to isolate, purify, and determine the chemical structure of the "hormones" of the anterior pituitary. However, even at this early time, bioassays were discovered, many by serendipity, that could be used to isolate potent fractions and to study the physiological actions of these substances.

One noteworthy example is the early work of Dr. Oscar Riddle (Fig. 1) and colleagues (8) involving the discovery of prolactin. Earlier reports from his laboratory in the late 1920s had described lactational-inducing effects of anterior pituitary extracts (9). However, at that time, only the growth-promoting and gonad-stimulating actions had been characterized (5). Riddle proposed a "third principle." His research was seminal as he isolated, developed a bioassay, and named the principle, prolactin (8). The key to Riddle's discovery was the bioassay he developed (9). He turned to an unlikely model for this assay, the pigeon crop sac, certainly one of the historically more interesting early bioassays.



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  		Fig. 1. Oscar Riddle. Courtesy of the Cold Spring Harbor Laboratory Archives.

 
Riddle became acquainted with pigeons and doves through his graduate studies with his mentor, Dr. Charles Whitman, at the University of Chicago. Whitman started his studies with pigeons in 1895; his interest in pigeons arose from his fascination with the birds that developed during his childhood. As a result of his studies, Whitman became a renowned avian physiologist. Riddle had an especially strong relationship with Whitman and, in fact, was responsible for getting a large collection of Whitman's studies published in 1919, nine years after Whitman's death. In many ways, Riddle carried on the legacy of pigeon research. For the field of endocrine physiology, this could not have been a better happenstance, since Riddle used the pigeon as the recipient for his pituitary extracts. Imagine his excitement when he observed that the crop sac thickened and secreted "milk" after injections of pituitary extracts into the pigeons.

Using the crop-sac assay, Riddle was able to isolate fractions from anterior pituitary extracts (obtained from colleagues throughout the country) that promoted milk secretion, thereby firmly establishing that the milk-secreting substance was distinct from growth-promoting and gonad-stimulating properties of the anterior pituitary extracts. The crop-sac assay allowed him to develop a relatively pure preparation of the substance, which he logically named prolactin (8). Armed with this preparation of relatively pure prolactin and the crop-sac assay, Riddle then turned his attention in the 1930s to studying the physiological effects of prolactin. At the time, the only response known for prolactin was stimulation of milk secretion, either from the mammary gland or the pigeon crop sac. Looking back over this remarkable achievement, it is very clear that without the pigeon crop sac assay, there very well could have been a delay of 20–30 years before the isolation of prolactin.

Even though the bioassay for prolactin was critical in our early understanding of the effects of prolactin, it lacked the requisite sensitivity to measure patterns of prolactin secretion in blood. It also was not suitable for use in clinical medicine. However, it was the only assay available for prolactin until the development of the technique of radioimmunoassay in the 1960s (3). In the early 1970s (7) a radioimmunoassay was developed for prolactin that ushered in the modern era of being able to provide detailed descriptions of the patterns of prolactin secretion in blood. Since then, many unusual aspects of prolactin have been described, such as the twice-daily surges of prolactin secretion observed during pregnancy and pseudopregnancy in the rat (6). Also, blood measurements of prolactin could be used clinically to diagnose pituitary tumors.

The early research of Riddle represented very hard work in the development and use of the crop-sac bioassay. The assay was very labor intensive and time consuming, requiring injections of hundreds of birds over several days. However, his work provided the groundwork for the decades of research that has followed (4). We now know that of the six anterior pituitary hormones, prolactin is noteworthy because it is under predominantly inhibitory control by the hypothalamus (1). Also, in addition to its milk-secretion effects, prolactin has effects on many body tissues; to date 300 separate biological activities for prolactin have been described (2). These activities vary from involvement in fluid balance homeostasis to metamorphosis in amphibians to support of corpus luteum function in rodents (2, 6).

The paper of Riddle reporting the discovery of prolactin (8) is truly a classic and represents the long tradition of the American Physiological Society in providing the foundation for important new areas of knowledge.

FOOTNOTES


Address for correspondence: M. S. Smith, Oregon National Primate Research Center, Oregon Health & Science Univ., 505 NW 185th Ave., Beaverton, OR 97006 (E-mail: smithsu{at}ohsu.edu)

REFERENCES

  1. Ben-Jonathan N and Hnasko R. Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 22: p.724–763, 2001.[Abstract/Free Full Text]
  2. Bern HA and Nicoll CA. The comparative endocrinology of prolactin. Recent Prog Horm Res 24: p.681–720, 1968.[Medline]
  3. Berson SA and Yalow RS. Immunoassay of protein and peptide hormones. Metabolism 13: p.1135–1153, 1964.
  4. Bole-Feysot C, Goffin V, Eldery M, Binart N, and Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19: p.225–268, 1998.[Abstract/Free Full Text]
  5. Evan HM and Simpson ME. Hormones of the anterior hypophysis. Am J Physiol 98: p.511–546, 1930.
  6. Freeman ME, Kanyicska B, Lerant A, and Nagy G. Prolactin: structure, function and regulation of secretion. Physiol Rev 80: p.1523–1631, 2000.[Abstract/Free Full Text]
  7. Neill JD and Reichert LE. Development of a radioimmunoassay for rat prolactin and evaluation of the NIAMD rat prolactin radioimmunoassay. Endocrinology 88: p.548–555, 1971.[Abstract/Free Full Text]
  8. Riddle O, Bates RW, and Dykshorn SW. The preparation, identification and assay of prolactin—a hormone of the anterior pituitary. Am J Physiol 105: p.191–216, 1933.[Free Full Text]
  9. Riddle O and Braucher PF. Control of the special secretion of the crop gland in pigeons by an anterior pituitary hormone. Am J Physiol 97: p.617–625, 1931.[Free Full Text]




This Article
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