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GONADOTROPINS OF THE ANTERIOR LOBE OF THE PITUITARY AND OF CHORIONIC TISSUE FREE

EARL T. ENGLE, Ph.D.; LOUIS LEVIN, Ph.D.
JAMA. 1941;116(1):47-52. doi:10.1001/jama.1941.62820010003013
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The concept of gonadotropic action of the anterior lobe of the pituitary gland arose from the experiments of Philip E. Smith in 1926, in which the treatment of immature rodents with implants of fresh anterior lobe produced follicular growth and the formation of corpora lutea. Similar effects were found at the same time in immature mice by Aschheim and Zondek, but Smith demonstrated that atrophy of the gonads follows hypophysectomy and that it may be prevented or the gonads repaired by treatment with fresh anterior pituitary implants.

Since this pioneer work, an amazing mass of literature concerning this subject has accumulated. It is beyond the scope of this chapter to consider all the work which has been reported. For such a comprehensive review the reader is referred to Van Dyke (1939).1 In the present article attention will be directed to those observations which appear to be most firmly established

REFERENCES

Van Dyke, H. B.: The Physiology and Pharmacology of the Pituitary Body , Chicago, University of Chicago Press, 1936;, vol. 1
1939, vol. 2.
Greep, R. O.; Van Dyke, H. B., and Chow, B. F.:  Separation in Nearly Pure Form of Luteinizing (Interstitial-Cell-Stimulating) and Follicle-Stimulating (Gametogenic) Hormones of the Pituitary Gland , J. Biol. Chem. 133:289 ( (March) ) 1940;.
Shedlovsky, T.; Rothen, A.; Greep, R. O.; Van Dyke, H. B., and Chow, B. F.:  The Isolation in Pure Form of the Interstitial Cell-Stimulating (Luteinizing) Hormone of the Anterior Lobe of the Pituitary Gland , Science 92:178 ( (Aug.) ) 1940;.
Evans, H. M.; Simpson, M. E., and Pencharz, R. I.:  (Interstitial-Cell-Stimulating) An Anterior Pituitary Gonadotropic Fraction (Interstitial-Cell-Stimulating) Specifically Stimulating the Interstitial Tissue of Testis and Ovary , Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Fevold, H. L.:  Extraction and Standardization of Pituitary Follicle-Stimulating and Luteinizing Hormones , Endocrinology 24:435 ( (April) ) 1939;.
Evans, H. M.; Simpson, M. E.; Tolksdorf, Sybylle, and Jensen, H.:  Biological Studies of the Gonadotropic Principles in Sheep Pituitary Substance , Endocrinology 25:529 ( (Oct.) ) 1939;.
Bunde, C. A., and Greep, R. O.:  Suppression of Persisting Corpora Lutea in Hypophysectomized Rats , Proc. Soc. Exper. Biol. & Med. 35:235 ( (Nov.) ) 1936;.
Greep, R. O.:  Pituitary Regulation of the Male Gonad , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Maxwell, L. C.:  The Quantitative and Qualitative Ovarian Response to Distributed Dosage with Gonadotropic Extracts , Am. J. Physiol. 110:458 ( (Dec.) ) 1934;.
Saunders, F. J., and Cole, H. H.:  On the Reliability of Present Methods for Characterizing Two Gonadotropic Hormones, Follicle-Stimulator and Luteinizer , Endocrinology 23:302 ( (Sept.) ) 1938;.
The designation of the "synergist" as a separate and distinct gonadotropic fraction no longer seems justified since Evans has admitted that the pituitary fraction designated by this term is the same as the follicle-stimulating fraction.
Du Shane, G. P.; Levine, W. T.; Pfeiffer, C. A., and Witschi, E.:  Experimental "Constant Oestrus" and the Notion of Antigonadotropic Hormones , Proc. Soc. Exper. Biol. & Med. 33:339 ( (Dec.) ) 1935;.
Cutuly, Eugene; McCullagh, D. R., and Cutuly, Elizabeth:  The Type and Degree of Gonadal Stimulation Induced in Hypophysectomized Male Rats Parabiotically Joined with Castrated, Cryptorchid, and Normal Partners , Endocrinology 21:241 ( (March) ) 1937;.
Cutuly, Eugene and Cutuly, Elizabeth C.:  Inhibition of Gonadotropic Activity by Sex Hormones in Parabiotic Rats , Endocrinology 22:568 ( (May) ) 1938;.
Greep, R. O.:  Pituitary Function in Parabiotic Triplet Rats , Proc. Soc. Exper. Biol. & Med. 44:214 ( (May) ) 1940;.
Rowlands, I. W.:  Selective Neutralization of the Luteinizing Activity of Gonadotropic Extracts of Pituitary by Anti-Sera , Proc. Roy. Soc., London, s. B 126:76 ( (Sept. 23) ) 1938;.
Fevold, H. L.:  The Gonadotropic Hormones , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Fevold, H. L.; Lee, M.; Hisaw, F. L., and Cohn, E. J.:  Studies in the Physical Chemistry of the Anterior Pituitary Hormones , Endocrinology 26:999 ( (June) ) 1940;.
Jensen, H.; Simpson, Miriam E.; Tolksdorf, Sybylle, and Evans, H. M.:  Chemical Fractionation of the Gonadotropic Factors Present in Sheep Pituitary , Endocrinology 25:57 ( (July) ) 1939;.
Evans, H. M.; Korpi, K.; Simpson, M. E.; Pencharz, R. I., and Wonder, D. H.:  On the Separation of the Interstitial Cell-Stimulating, Luteinizing and Follicle-Stimulating Fractions of the Anterior Pituitary Gonadotropic Complex , Univ. California Publ. Anat. 1:255, 1936;.
Wallen-Lawrence, Zonja:  Proof of the Existence of a Follicle-Stimulating and a Luteinizing Hormone in the Anterior Lobe of the Pituitary Body , J. Pharmacol. & Exper. Therap. 51:263 ( (July) ) 1934;.
Chow, B. F.; Greep, R. O., and Van Dyke, H. B.:  The Effects of Digestion by Proteolytic Enzymes on the Gonadotrophic and Thyrotrophic Potency of Anterior Pituitary Extract , J. Endocrinol. 1:440 ( (Dec.) ) 1939;.
Hamburger, Christian:  Studies on Gonadotropic Hormones from the Hypophysis and Chorionic Tissue, with Special Reference to Their Differences , Acta path. et microbiol. Scandinav. , 1933;, (supp. 17) .
Tyndale, H. H.; Levin, Louis, and Smith, P. E.:  Responses of Normal and Hypophysectomized Immature Rats to Menopause Urine Injections , Am. J. Physiol. 124:174 ( (Oct.) ) 1938;.
Kurzrok, Raphael; Kirkman, Irene J., and Creelman, Margaret:  Studies Relating to the Time of Human Ovulation , Am. J. Obst. & Gynec. 28:319 ( (Sept.) ) 1934;.
Frank, R. T., and Salmon, U. J.:  Gonadotropic Blood and Urine Cycles in Normal Menstruating Women , Proc. Soc. Exper. Biol. & Med. 32:1237 ( (May) ) 1935;.
Smith, G. V., and Smith, O. W.:  The Urinary Excretion of Estrogenic and Gonadotropic Hormones During Menstrual Cycles, the Period of Conception and Early Pregnancy , New England J. Med. 215:908 ( (Nov. 12) ) 1936;.
D'Amour, F. E.; Funk, Dorothy, and Liverman, Helen:  Daily Gonadotropic Hormone Tests During Fifty Complete Menstrual Cycles , Am. J. Obst. & Gynec. 37:940 ( (June) ) 1939;.
Werner, S. C.:  A Quantitative Study of the Urinary Excretion of Hypophysial Gonadotropin, Estrogen and Androgen of Normal Women , J. Clin. Investigation , to be published.
Levin, Louis, and Tyndale, H. H.:  The Quantitative Assay of "Follicle-Stimulating" Substances , Endocrinology 21:619 ( (Sept.) ) 1937;.
D'Amour, F. E.:  A Qualitative Study of Normal Gonadotropin , Am. J. Physiol. 127:649 ( (Nov.) ) 1939;.
Leathem, J. H., and Levin, Louis: The Gonadotropic Action of Normal Male Urine Extract on the Ovaries of Normal and Hypophysectomized Immature Rats and of Immature Mice, to be published.
Engle, E. T.:  Gonadotropic Substances of Blood, Urine and Other Body Fluids , in Allen, Edgar; Danforth, C. H., and Doisy, E. A.: Sex and Internal Secretions , Baltimore, Williams & Wilkins Company, 1939;.
Leonard, S. L., and Smith, P. E.:  Responses of the Reproductive System of Hypophysectomized Rats to Injections of Pregnancy-Urine Extracts: II. The Female , Anat. Rec. 58:175 ( (Jan. 25) ) 1934;.
Hamblen, E. C.: Endocrine Gynecology , Springfield, Ill., Charles C. Thomas, Publisher, 1939;.
Smith, P. E., and Leonard, S. L.:  Responses of the Reproductive System of Hypophysectomized and Normal Rats to Injections of Pregnancy-Urine Extracts; I. The Male , Anat. Rec. 58:145 ( (Jan. 25) ) 1934;.
Walsh, E. L.; Cuyler, W. K., and McCullagh, D. R.:  The Physiologic Maintenance of the Male Sex Glands; The Effect of Androtin on Hypophysectomized Rats , Am. J. Physiol. 107:508 ( (Feb.) ) 1934;.
Nelson, W. O.:  Some Factors Involved in the Control of the Gametogenic and Endocrine Functions of the Testis , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Nelson, W. O.:  Re-Initiation of Spermatogenesis in Hypophysectomized Rats , Am. J. Physiol. 129:P430 ( (May) ) 1940;.
Smith, P. E.:  Comparative Effects of Hypophysectomy and Therapy on the Testes of Monkeys and Rats , in Brouha, L.: Les hormones sexuelles , Paris, Hermann & Cie, 1938;, pt. (3) , L'hypophyse.
Scowen, E. F.:  The Effects of Androsterone and Testosterone on the Testes of Hypophysectomized Guinea Pigs , Anat. Rec. 70 ( (supp. 3) ):71 (March) 1938;.
Leathem, J. H.:  Responses of Hypophysectomized Immature Female Rats to Mare Serum Hormone , Proc. Soc. Exper. Biol. & Med. 42:590 ( (Nov.) ) 1939;.
Smith, P. E.: Unpublished data.
Evans, H. M.; Pencharz, R. I.; Simpson, M. E., and Meyer, K.:  Repair of the Reproductive Mechanism in Hypophysectomized Male Rats , in Lueschner, A. O., and Teggart, F. J.: Memoirs of the University of California , Berkeley, Calif., University of California Press, 1933;, vol. 11, p. 301.
Liu, S. H., and Noble, R. L.:  The Effects of Extracts of Pregnant Mare Serum and Human Pregnancy Urine on the Reproductive System of Hypophysectomized Male Rats , J. Endocrinol. 1:7 ( (June) ) 1939;.
Webster, E. C., and Leathern, J. H.: Responses of Hypophysectomized and Normal Male Guinea Pigs to Mare Serum Hormone, to be published.
Smith, P. E.:  Presidental Address , read before the Twenty-Fourth Annual Scientific Session of the Association for the Study of Internal Secretions , New York, 1940;.
Evans, H. M.; Korpi, K.; Simpson, M. E., and Pencharz, R. I.:  Fractionation of the Gonadotropic Hormones in Pregnant Mare Serum by Means of Ammonium Sulphate , Univ. California Publ. Anat. 1:275, 1936;.
Pencharz, R. I.:  Factors Influencing Ovarian Response of Normal and Hypophysectomized Rat to Pregnant Mare Serum , Proc. Soc. Exper. Biol. & Med. 42:525 ( (Nov.) ) 1939;.
Leathem, J. H.: The Mode of Administration as an Influence on the Effectiveness of Mare Serum Hormone in Hypophysectomized Rats, to be published.

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Van Dyke, H. B.: The Physiology and Pharmacology of the Pituitary Body , Chicago, University of Chicago Press, 1936;, vol. 1
1939, vol. 2.
Greep, R. O.; Van Dyke, H. B., and Chow, B. F.:  Separation in Nearly Pure Form of Luteinizing (Interstitial-Cell-Stimulating) and Follicle-Stimulating (Gametogenic) Hormones of the Pituitary Gland , J. Biol. Chem. 133:289 ( (March) ) 1940;.
Shedlovsky, T.; Rothen, A.; Greep, R. O.; Van Dyke, H. B., and Chow, B. F.:  The Isolation in Pure Form of the Interstitial Cell-Stimulating (Luteinizing) Hormone of the Anterior Lobe of the Pituitary Gland , Science 92:178 ( (Aug.) ) 1940;.
Evans, H. M.; Simpson, M. E., and Pencharz, R. I.:  (Interstitial-Cell-Stimulating) An Anterior Pituitary Gonadotropic Fraction (Interstitial-Cell-Stimulating) Specifically Stimulating the Interstitial Tissue of Testis and Ovary , Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Fevold, H. L.:  Extraction and Standardization of Pituitary Follicle-Stimulating and Luteinizing Hormones , Endocrinology 24:435 ( (April) ) 1939;.
Evans, H. M.; Simpson, M. E.; Tolksdorf, Sybylle, and Jensen, H.:  Biological Studies of the Gonadotropic Principles in Sheep Pituitary Substance , Endocrinology 25:529 ( (Oct.) ) 1939;.
Bunde, C. A., and Greep, R. O.:  Suppression of Persisting Corpora Lutea in Hypophysectomized Rats , Proc. Soc. Exper. Biol. & Med. 35:235 ( (Nov.) ) 1936;.
Greep, R. O.:  Pituitary Regulation of the Male Gonad , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Maxwell, L. C.:  The Quantitative and Qualitative Ovarian Response to Distributed Dosage with Gonadotropic Extracts , Am. J. Physiol. 110:458 ( (Dec.) ) 1934;.
Saunders, F. J., and Cole, H. H.:  On the Reliability of Present Methods for Characterizing Two Gonadotropic Hormones, Follicle-Stimulator and Luteinizer , Endocrinology 23:302 ( (Sept.) ) 1938;.
The designation of the "synergist" as a separate and distinct gonadotropic fraction no longer seems justified since Evans has admitted that the pituitary fraction designated by this term is the same as the follicle-stimulating fraction.
Du Shane, G. P.; Levine, W. T.; Pfeiffer, C. A., and Witschi, E.:  Experimental "Constant Oestrus" and the Notion of Antigonadotropic Hormones , Proc. Soc. Exper. Biol. & Med. 33:339 ( (Dec.) ) 1935;.
Cutuly, Eugene; McCullagh, D. R., and Cutuly, Elizabeth:  The Type and Degree of Gonadal Stimulation Induced in Hypophysectomized Male Rats Parabiotically Joined with Castrated, Cryptorchid, and Normal Partners , Endocrinology 21:241 ( (March) ) 1937;.
Cutuly, Eugene and Cutuly, Elizabeth C.:  Inhibition of Gonadotropic Activity by Sex Hormones in Parabiotic Rats , Endocrinology 22:568 ( (May) ) 1938;.
Greep, R. O.:  Pituitary Function in Parabiotic Triplet Rats , Proc. Soc. Exper. Biol. & Med. 44:214 ( (May) ) 1940;.
Rowlands, I. W.:  Selective Neutralization of the Luteinizing Activity of Gonadotropic Extracts of Pituitary by Anti-Sera , Proc. Roy. Soc., London, s. B 126:76 ( (Sept. 23) ) 1938;.
Fevold, H. L.:  The Gonadotropic Hormones , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Fevold, H. L.; Lee, M.; Hisaw, F. L., and Cohn, E. J.:  Studies in the Physical Chemistry of the Anterior Pituitary Hormones , Endocrinology 26:999 ( (June) ) 1940;.
Jensen, H.; Simpson, Miriam E.; Tolksdorf, Sybylle, and Evans, H. M.:  Chemical Fractionation of the Gonadotropic Factors Present in Sheep Pituitary , Endocrinology 25:57 ( (July) ) 1939;.
Evans, H. M.; Korpi, K.; Simpson, M. E.; Pencharz, R. I., and Wonder, D. H.:  On the Separation of the Interstitial Cell-Stimulating, Luteinizing and Follicle-Stimulating Fractions of the Anterior Pituitary Gonadotropic Complex , Univ. California Publ. Anat. 1:255, 1936;.
Wallen-Lawrence, Zonja:  Proof of the Existence of a Follicle-Stimulating and a Luteinizing Hormone in the Anterior Lobe of the Pituitary Body , J. Pharmacol. & Exper. Therap. 51:263 ( (July) ) 1934;.
Chow, B. F.; Greep, R. O., and Van Dyke, H. B.:  The Effects of Digestion by Proteolytic Enzymes on the Gonadotrophic and Thyrotrophic Potency of Anterior Pituitary Extract , J. Endocrinol. 1:440 ( (Dec.) ) 1939;.
Hamburger, Christian:  Studies on Gonadotropic Hormones from the Hypophysis and Chorionic Tissue, with Special Reference to Their Differences , Acta path. et microbiol. Scandinav. , 1933;, (supp. 17) .
Tyndale, H. H.; Levin, Louis, and Smith, P. E.:  Responses of Normal and Hypophysectomized Immature Rats to Menopause Urine Injections , Am. J. Physiol. 124:174 ( (Oct.) ) 1938;.
Kurzrok, Raphael; Kirkman, Irene J., and Creelman, Margaret:  Studies Relating to the Time of Human Ovulation , Am. J. Obst. & Gynec. 28:319 ( (Sept.) ) 1934;.
Frank, R. T., and Salmon, U. J.:  Gonadotropic Blood and Urine Cycles in Normal Menstruating Women , Proc. Soc. Exper. Biol. & Med. 32:1237 ( (May) ) 1935;.
Smith, G. V., and Smith, O. W.:  The Urinary Excretion of Estrogenic and Gonadotropic Hormones During Menstrual Cycles, the Period of Conception and Early Pregnancy , New England J. Med. 215:908 ( (Nov. 12) ) 1936;.
D'Amour, F. E.; Funk, Dorothy, and Liverman, Helen:  Daily Gonadotropic Hormone Tests During Fifty Complete Menstrual Cycles , Am. J. Obst. & Gynec. 37:940 ( (June) ) 1939;.
Werner, S. C.:  A Quantitative Study of the Urinary Excretion of Hypophysial Gonadotropin, Estrogen and Androgen of Normal Women , J. Clin. Investigation , to be published.
Levin, Louis, and Tyndale, H. H.:  The Quantitative Assay of "Follicle-Stimulating" Substances , Endocrinology 21:619 ( (Sept.) ) 1937;.
D'Amour, F. E.:  A Qualitative Study of Normal Gonadotropin , Am. J. Physiol. 127:649 ( (Nov.) ) 1939;.
Leathem, J. H., and Levin, Louis: The Gonadotropic Action of Normal Male Urine Extract on the Ovaries of Normal and Hypophysectomized Immature Rats and of Immature Mice, to be published.
Engle, E. T.:  Gonadotropic Substances of Blood, Urine and Other Body Fluids , in Allen, Edgar; Danforth, C. H., and Doisy, E. A.: Sex and Internal Secretions , Baltimore, Williams & Wilkins Company, 1939;.
Leonard, S. L., and Smith, P. E.:  Responses of the Reproductive System of Hypophysectomized Rats to Injections of Pregnancy-Urine Extracts: II. The Female , Anat. Rec. 58:175 ( (Jan. 25) ) 1934;.
Hamblen, E. C.: Endocrine Gynecology , Springfield, Ill., Charles C. Thomas, Publisher, 1939;.
Smith, P. E., and Leonard, S. L.:  Responses of the Reproductive System of Hypophysectomized and Normal Rats to Injections of Pregnancy-Urine Extracts; I. The Male , Anat. Rec. 58:145 ( (Jan. 25) ) 1934;.
Walsh, E. L.; Cuyler, W. K., and McCullagh, D. R.:  The Physiologic Maintenance of the Male Sex Glands; The Effect of Androtin on Hypophysectomized Rats , Am. J. Physiol. 107:508 ( (Feb.) ) 1934;.
Nelson, W. O.:  Some Factors Involved in the Control of the Gametogenic and Endocrine Functions of the Testis , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5.
Nelson, W. O.:  Re-Initiation of Spermatogenesis in Hypophysectomized Rats , Am. J. Physiol. 129:P430 ( (May) ) 1940;.
Smith, P. E.:  Comparative Effects of Hypophysectomy and Therapy on the Testes of Monkeys and Rats , in Brouha, L.: Les hormones sexuelles , Paris, Hermann & Cie, 1938;, pt. (3) , L'hypophyse.
Scowen, E. F.:  The Effects of Androsterone and Testosterone on the Testes of Hypophysectomized Guinea Pigs , Anat. Rec. 70 ( (supp. 3) ):71 (March) 1938;.
Leathem, J. H.:  Responses of Hypophysectomized Immature Female Rats to Mare Serum Hormone , Proc. Soc. Exper. Biol. & Med. 42:590 ( (Nov.) ) 1939;.
Smith, P. E.: Unpublished data.
Evans, H. M.; Pencharz, R. I.; Simpson, M. E., and Meyer, K.:  Repair of the Reproductive Mechanism in Hypophysectomized Male Rats , in Lueschner, A. O., and Teggart, F. J.: Memoirs of the University of California , Berkeley, Calif., University of California Press, 1933;, vol. 11, p. 301.
Liu, S. H., and Noble, R. L.:  The Effects of Extracts of Pregnant Mare Serum and Human Pregnancy Urine on the Reproductive System of Hypophysectomized Male Rats , J. Endocrinol. 1:7 ( (June) ) 1939;.
Webster, E. C., and Leathern, J. H.: Responses of Hypophysectomized and Normal Male Guinea Pigs to Mare Serum Hormone, to be published.
Smith, P. E.:  Presidental Address , read before the Twenty-Fourth Annual Scientific Session of the Association for the Study of Internal Secretions , New York, 1940;.
Evans, H. M.; Korpi, K.; Simpson, M. E., and Pencharz, R. I.:  Fractionation of the Gonadotropic Hormones in Pregnant Mare Serum by Means of Ammonium Sulphate , Univ. California Publ. Anat. 1:275, 1936;.
Pencharz, R. I.:  Factors Influencing Ovarian Response of Normal and Hypophysectomized Rat to Pregnant Mare Serum , Proc. Soc. Exper. Biol. & Med. 42:525 ( (Nov.) ) 1939;.
Leathem, J. H.: The Mode of Administration as an Influence on the Effectiveness of Mare Serum Hormone in Hypophysectomized Rats, to be published.
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