CURRENT CONCEPTS ON THE CHEMICAL BIOLOGY OF PITUITARY HORMONES CHOH HAO LI* The hormones of the pituitary gland (Table i) are either proteins or polypeptides. Their molecular weight varies from 1,000 to 50,000. The complete structure ofsome ofthese hormones has become known (Table 2), and a few ofthem have been synthesized. Investigations on the chemistry and biology ofthese hormoneshave given us some important general concepts in the field ofmolecular endocrinology. It is the purpose ofthis article to outline these concepts and to present the experimental data from which these concepts were derived. Hormones Having the Same Biological Function Are Not Necessarily Chemically Identical There are three gonad-stimulating hormones (gonadotropins) in the anterior pituitary, namely, follicle-stimulating (FSH), interstitial-cell-stimulating (ICSH), and lactogenic (LtH) hormones. In the female, FSH causes the development ofimmature ovarian follicles, bringing them to maturity. ICSH in turn stimulates the mature follicles to form estrogens and gives the follicle impetus for further development as a corpus luteum. The growing corpus luteum is then brought to maturity by LtH. The secretion of progesterone from the functional corpora lutea is under the control ofLtH. Among these gonadotropins, ICSH is the most important for the growth and development of the male sexual characters. It stimulates the seminiferous tubules and interstitial cells in the male, eliciting the production of androgen, which in turn causes enlargement of the accessory organs . Spermatogenesis is also under the control ofICSH. This hormone * Hormone Research Laboratory, University of California, San Francisco. A portion of this essay was presented in March, 1963, when the author was elected Faculty Research Lecturer for 1962-63. Research has been supported in part by the U.S. Public Health Service and the American Cancer Society. 498 Choh Hao Li · Pituitary Hormones Perspectives in Biology and Medicine · Spring 1968 TABLE 1 Hormones of the Pituitary Gland Lobe of Pituitary Hormones Principal Function Posterior ...... Intermediate. . . Anterior. Oxytocin Vasopressin Melanotropins [Somatotropin (growth hormone) Mammotropin (prolactin, lactogenic hormone) Interstitial-cell-stimulating hormone (luteinizing hormone ) Follicle-stimulating hormone Thyrotropin Adrenocorticotropin Lipotropin Contraction of the smooth muscle of the uterus; milk ejection from the lactating gland Constriction of the smooth musculature of the arteries; retention of water Darkening of skin General body growth; anabolic effect on various tissues of the body; effects on fat, carbohydrate, and protein metabolisms Development and lactation of the mammary gland Development of interstitial cells in the ovary and testis Development of follicles in the ovary and seminiferous tubules in the testis Production and secretion of thyroid hormones Production and secretion of adrenal cortical hormones Release of lipid from adipose tissues TABLE 2 Pituitary Hormones of Known Structures Hormones No. of Amino Acids Source Oxytocin ............... Vasopressin............. ACTH................. /3-MSH ................ a-MSH ................ LPH................... Human growth hormone. . 1,2 3,4 5,6 7,8 9 10 11 1.V. DU VlGNEAUD, C Reseler, J. M. Swan, C. W. Roberts, P. G. Katsoyannis, and S. Gordan. J. Amer. Chem. Soc, 75:4878, 1953. 2.H. Tuppy. Biochim. biophys. acta, 11:449, 1953. 3.V. du Vigneaud, H. C. Lawler, and E. A. PopenOe. J. Amer. Chem. Soc, 75:4880, 1953. 4.R. Aches and J. Chauvet. Biochim. biophys. acta, 12:487, 1953. 5.K. S. Howard, R. G. Shepherd, E. A. Eigner, D. S. Davis, and P. H. Bell. J. Amer. Chem. Soc, 77:3419, 1955. 6.C. H. Li, 1. 1. Geschwind, R. D. Cole, I. D. Raacke, J. I. Harris, and J. S. Ddcon. Nature, 176:687, 1955. 7.J. I. Harris and P. Roos. Nature, 178:90, 1956. 8.I. I. Geschwind, C H. Li, and L. Barnafi. J. Amer. Chem. Soc, 78:4494, 1956. 9.J. I. Harris and A. B. Lerner. Nature, 179:1346, 1957. 10.C. H. Li, L. Barnafi, M. Chretien, and D. Chung. Nature, 208: 1093, 1965. 11.C. H. Li, W.-K. Liu, and J. S. Ddcon. J. Amer. Chem. Soc, 88: 2010, 1966. has been obtained in apparently pure form from sheep [1-3] and human [4] pituitary extracts. The biological activity of the human and ovine ICSH has been assayed by the ventral prostate test [5]. As shown in Table 3, the dose-response relationship [6] of the human hormone...