The concept that proteins, in addition to steroid hormones, of gonadal origin could play a role in the inhibition of gonadatropin secretion from the anterior lobe of the pituitary was proposed more than 65 yr ago. Only recently, however, has the elucidation of the chemistry and physiology of these proposed gonadal hormones actually been achieved. Mottram and Cramer (1) reported pituitary hypertrophy as determined by the appearance of so-called castration cells in the anterior lobe of pituitary after treatment of the testes with radium. The removal of the testes leads to the development of highly vacuolated, signet-shaped basophil cells in the pituitary (2), termed castration cells, demonstrating a reciprocal relationship between the pituitary and the gonads and suggesting that a secretion of the testes has an inhibitory effect on the pituitary (3). The pituitary hypertrophy after castration or irradiation of the testes was postulated to be due to a lack of some substance from the seminal epithelium because vasectomy totally prevented the morphological changes, suggesting that the status of the seminiferous tubules might be responsible for the observed changes in the pituitary gland.