Is the Thymus an Endocrine Gland?: Old Problem, New Data

IS THE THYMUS AN ENDOCRINE GLAND? OLD PROBLEM, NEW DATA ABRAHAM WHITE and ALLAN L. GOLDSTEIN* It seems appropriate in a volume honoring Dr. Gregory Pincus, a distinguished endocrinologist, to have a contribution that will consider briefly the history ofa gland studied by pioneers in experimental physiology and medicine and to indicate more recent developments which not only have attracted renewed attention to this anatomical structure but suggest it should be added to the established list ofendocrine glands. It is the purpose of this essay to examine some of the evidence for a possible role ofthe thymus as an endocrine organ. This will be approached by assessing the extent to which studies ofthe thymus have provided data confirming the postulates generally agreed necessary to establish that a given anatomical structure is an endocrine organ. These data are generally sought in the following experimental stages: (i) extirpation ofthe tissue or organ with subsequent evidence ofphysiological or biochemical alterations and deficiencies; (2) replacement therapy, that is, efforts to replace the extirpated structure by transplantation ofthe organ and by administration of suitable extracts of the removed tissue; (3) administration ofexcessive amounts ofan extract ofthe gland to normal animals in order to study alterations which may result from an exaggerated supply of the * Department of Biochemistry, Albert Einstein College ofMedicine, Yeshiva University, New York, New York 10461. The data from our laboratory referred to in this paper have been obtained in investigations contributed to by the continuing efforts ofDr. Sipra Banerjee and the able assistance ofMiss Norma Robert, Mrs. Florence Slater, and Mr.James Oliver. An earlier interest in the thymus as an endocrine gland was reawakened several years ago by Dr.JeromeJ. Klein, who participated in our preliminary studies ofthymic extracts and in the initial development ofa procedure for the in vivo assay ofthymic preparations. Our investigations have been supported by grants from the National Cancer Institute, National Institutes of Health, USPHS (CA-07470), the American Cancer Society (P-68), the National Science Foundation (GB-2711), and the Damon Runyon Fund for Cancer Research (DRG-920). The helpful financial and technical support of Syntex Laboratories, Inc., are also gratefully acknowledged. Dr. Allan L. Goldstein is a recipient ofa Career Scientist Award of the Health Research Council of the City of New York under contract I-519. 475 hormonal products ofthe gland. Data from studies described under ? and 3 may be compared with, and related to, clinical states which have been described as due to hypo- or hyperfunctioning, respectively, of the gland; (4) isolation in pure form and chemical characterization of the active hormonal principle or principles as these occur in the tissue oforigin and in the blood; (5) demonstration that the isolated principle or principles when administered can substitute effectively, in the absence of the gland in question, for the functions normally dependent upon the presence ofthe gland; (6) synthesis ofthe hormone, with subsequent demonstration that the synthetic product has all ofthe chemical and physiological properties of the natural secretion. For the thymus gland, it is possible at this time to assemble limited but suggestive evidence supporting postulates 1 and 2 above. Initial studies, with crude extracts ofthymic tissue, indicate that postulates 4 and 5 may find some support from the preliminary experimental data. The tentative conclusion that the thymus is an endocrine gland appears warranted. It is evident that, in the young ofseveral species, the thymus gland fulfils functions which are suggestive ofan endocrine role. In the adult animal, the presence of the thymus gland is not life determining, but there does slowly develop, in its absence, suggestions ofan impaired immunological response which is related presumably to the slow loss ofthe pool oflonglived , immunologically competent lymphocytes. This impaired immunological responsiveness in adult thymectomized animals is more pronounced ifthe normal complement oflymphoid tissue and circulating lymphocytes is drastically reduced by procedures which involute lymphoid tissue, notably exposure to whole body X-irradiation. The resurgence in the past decade of scientific interest in the thymus should provide more conclusive evidence for or against each ofthe above postulates and lead to a more unequivocal answer as to whether the thymus is an endocrine gland. Let us examine the evidence presently available. i. Effects ofExtirpation ofthe...