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

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. 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. Look-