Permanent changes in the testis were induced in mice given daily injections of estradiol-17β for 15 days starting on the day of birth, 20μg for the first 10 days and 40μg for the following 5 days. Sequential changes in the testis during or after the neonatal estrogen injections were examined under an electronmicroscope. One to seven daily injections of estrogen caused no change in the testis. In 10-to 20-day-old mice which had been given estrogen injections for 10-15 postnatal days, however, multinucleated gigantic spermatocytes were found in high frequency in the seminiferous tubules, and plasma membranes of both the germ cells and the myoid cells of the lamellated connective tissue surrounding the tubules frequently became discontinuous or underwent disintegration. Partial disorganization took place in some of the tubules. In 30-day-old mice which had been given estrogen injections for 15 postnatal days, the testis contained atrophic Leydig cells and the tubules with a thin seminiferous epithelium consisting of spermatogonia, spermatocytes and immature Sertoli cells.

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Plasma LH and FSH responses to the intravenous injection of synthetic LH-RH were studied in 18 normal males and in 24 patients with hypogonadism of various etiologies. Intravenous injection of 100, 200 and 400μg of LH-RH into normal adult males caused a dose-dependent rise in plasma LH and FSH. Plasma LH rose significantly in all subjects after 100μg of LH-RH, whereas 200 ti 400μg were necessary to achieve a consistent rise in plasma FSH.
In 7 patients with hypergonadotropic hypogonadism, plasma LH and FSH levels were elevated with a marked and sustained response to 100μg of LH-RH.
In 9 patients with isolated gonadotropin deficiency, plasma LH and FSH levels were either undetectable or low and their responses to 100μg of LH-RH were absent or limited.
In 5 of these patients, intravenous infusion of 400μg of LH-RH for 7 to 21 successive days improved plasma LH and FSH responsiveness to LH-RH, whereas the infusion for 2 days in 2 patients was not effective.
In 8 patients with failure of sexual maturation due to organic hypothalamohypophyseal lesions, plasma LH and FSH responses to 100μg of LH-RH were normal in one and low or absent in the remaining patients. In one patient with ectopic pinealoma, a diminished response of LH and FSH to LH-RH was normalized after 7 successive days treatment with the intravenous infusion of 400μg of LH-RH.
Synthetic LH-RH test is a useful tool for the differential diagnosis of hypogonadism. It is not always possible, however, to differentiate the hypothalamic from pituitary lesions by a single LH-RH test, because diminished response to LH-RH may indicate either pituitary lesions or pituitary hyporesponsiveness due to long-standing deficiency of endogenous LH-RH. In this regard, prolonged LH-RH stimulation test may help to differentiate between hypothalamic and pituitary lesions.

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At the operation carried out primarily for removal of thyroid nodules, a firm lesion less than 1 cm in diameter was incidentally found in the remnant thyroid tissue in two cases. With suspicion of an occult carcinoma of the thyroid, partial thyroidectomy was performed. Microscopically the lesion was proved to be subacute thyroiditis. Retrospective review of the clinical and laboratory findings revealed nothing to suggest the coexistence of the inflammatory process. Postoperatively no recurrence of thyroiditis was seen in the remaining thyroid tissue. These cases imply the presence of patients with subacute thyroiditis which may proceed subclinically throughout the course.

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Neonatal female mice were given subcutaneous implants of the anterior pituitary from young male donors of the same inbred colony. Similar mice given an isograft of a piece of the submaxillary gland served as controls. When examined at the age of 1, 3 or 5 months, the isografted tissues were not recovered from any of these animals. Correlation analyses of estrous cycles were carried out. Studies of the autocorrelation function revealed that, in a majority of mice receiving pituitary isografts, their estrous cycles were irregular, characterized by prolonged vaginal estrus and/or prolonged diestrus continuing for periods of different length. The mean weight of the pituitary in situ was significantly smaller in these animals than that in the control mice. A similar fall of pituitary weights also occurred in mice ovariectomized on the day of pituitary implantation. This fact suggests that the pituitary isograft directly inhibits the growth of the pituitary in situ but not indirectly, via the ovaries. At 5 months of age, the ovaries of mice given pituitary grafts were enlarged, having so many corpora lutea, as compared with those of the control animals. This finding suggests that the neonatal pituitary implantation resulted in an increased secretion of gonadotropins from the pituitary in situ. In mice which had been given pituitary implants and showed prolonged, though not persistent, vaginal diestrus, the mammary glands contained well-developed branching ducts with a number of isolated alveoli. The pituitaries in situ appeared to have been permanently affected by neonatal pituitary isografts.

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In order to elucidate the existence of circadian rhythm in serum LH, FSH and prolactin in male rats, serum LH, FSH and prolactin levels in adult male rats of Holtzman strain were determined at 2-hrs intervals under the light control from 5:00 A.M. to 7:00 P.M. using NIAMD rat LH, FSH and prolactin radioimmunoassay kits.
A manifest circadian rhythm was demonstrated in serum LH and FSH levels. Serum LH levels showed the peak at 11:00 P.M. and the minimal level at 5:00 A.M. Serum FSH showed high levels from 7:00 P.M. to 3:00 A.M. in the dark period, then a sharp decline at 5:00 A.M. and remained in low levels during light period (7:00 A.M. to 5:00 P.M.). No circadian rhythm in serum prolactin was observed in adult male rats.
These data demonstrate that LH and FSH secretion from the male rat pituitary shows the high values at night or dark time and the low values at day or light time. It is noteworthy that these circadian rhythm in LH and FSH secretion coincides well with the circadian rhythm in sexual behavior of male rats.

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Thyrotrophs, LH-and FSH-gonadotrophs have long been universally believed to be the three independent types of basophils responsible for production of corresponding hormones. In our preparations of normal rat pituitaries stained with aldehyde thionin-PAS-orange G, however, cell type distinction among these three kinds of basophils based on the staining property was found to be almost impossible, because of the intermediate forms frequently encountered, suggesting possible transformation of basophils among these types. The LH-gonadotroph may be, in our opinion, one of the intermediate forms between thyrotrophs and FSH-gonadotrophs. The same enlarged polygonal thyrotrophlike cell was studied by optical and electron microscopy on the adjacent two slices. Their intracellular thioniophilic site corresponds with accumulation of granules on the electron microscopic level. Electron density of these granules varied from low to high in each cell, sometimes giving the picture of haloed granules. Polygonal lean basophils with a row of granules with the diameter of 100-150mμ along the plasmamembrane were identified as the immature basophils, but not as the thyrotrophs. The same ovoid LH-gonadotrophlike cell was examined by optical and electron microscopy on the adjacent two slices. According to characteristics of their fine structure, they may be nothing but the young FSH-gonadotroph-like cells with scanty round vesicles and imperfect Golgi-ring. When chromophobes dissociated and collected with negligible contamination with granulated cells were cultured in the media added with a small amount of TRH or LH-RH, some of them were converted into FSH-gonadotroph-like cells. “Cell conversion” is thought to take place similarly from chromophobes to the terminal FSH-gonadotroph-like cells via either thyrotroph-like or LH-gonadotroph-like cells, regardless of the kind and dose of used RH. Based on these findings, the entire life stage of basophils originating from chromophobes was demonstrated in a system in vitro along with hormone bioassays of explants and media. Such “cell-metamorphosis” may follow the order of immature basophil (Type I) →thyrotroph-like cells (Type II) →LH-gonadotroph-like cells (Type III) →FSH-gonadotroph-like cells (TypeIV) →degenerating cells. The course of life stage of cultured chromophobes was as long as 30 or 50 days with the remarkable variation due to the dose of the added hormones. Continuous, stepwise intravenous injections of TRH for 7 hr occasionally gave rise to some castration-like effect on the basophils in rats. In systems not only in vitro but also in vivo, the life stage of the cells originating from chromophobes might progress chronically along the basophil-axis. When chromophobes in vivo transform into the thyrotroph-like cells, they could start to operate repeatedly their own short term secretory cycles. The fine structures of various types of basophils involved in a secretory cycle were demonstrated in the normal rats and those injected with TRH and LH-RH. FSH-gonadotroph-like cells filled with the expanded round vesicles tend to rapidly multiply within 5min after an injection of TRH or LH-RH; LH-gonadotrophlike and thyrotroph-like cells, containing the numerous granules associated with haloed granules and closed ER, become the predominant component of basophils of the glands within 10 (TRH) or 30min (LH-RH); optical and electron microscopic changes of three kinds of basophils return to the prestimulated status within 60 (TRH) and 180min (LH-RH). Two possibilities are discussed concerning the secretory cycle: One deals with only one secretory cycle common to the all types of basophils, and the other with three separated secretory cycles with regard to the thyrotroph, LH-and FSH-gonadotroph respectively.

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Development of acidophils was investigated electron microscopically in pituitaries from the rat embryos on the 15th, 17th, 18th and 20th day of gestation and from the neonatal and postnatal rats on the 1st, 3rd, 4th, 6th, 12th and 18th day of birth. Pituitary agranular primordial cells are the stem cells from which acidophils develop. During embryonic life, the male is more advanced in differentiation of primordial cells than the female. Initial granulation begins to take place in “ambiguous cells” (Yoshimura et al., 1970) on the 17th day of gestation as a row of minute granules about 50 mμ along the plasmamembrane. Incidence of ambiguous cells with various shapes is higher in the male than in the female. During embryonic period, only a small number of immature acidophils have developed from ambiguous cells despite spherical enlargement of cell-bodies where dense granules maintain their size within the proximity of 250 mμ. Most of ambiguous cells tend to transform into immature basophils, and even gonadotroph-like basophils have accumulated during the latest pregnancy. On the other hand many immature acidophils emerge directly from primordial cells without the mediation of ambiguous cells. In a certain primordial cells, a row of dense granules as large as 130-200 mμ in diameter suddenly appear along the plasmamembrane on the 18th day of gestation. In equilibrium with the prompt increase in the cell number, their granules rapidly increase in dimension and their maximal size reaches 250 mμ towards the end of fetal period. Postnatal development of acidophils is quite quick as to the population and granulation in both sexes. Numerous immature acidophils, not always spherical but somewhat elongated, develop appositionally from primordial cells. Appearance of a row of large granules of 200-250 mμ along the plasmamebrane of primordial cells seems to be related to morphological representation for the main developmental process of acidophils. Granules in immature acidophils increase in number, their size being persistently less than 200 mμ up to the 6th postnatal day. Enlarged spherical premature acidophils containing numerous granules of 200-300mμ in diameter begin to appear on the 12th day. So-called somatotrophs identical with the fully developed acidophils filled with large granules of about 350 mμ start to appear on the 18th day of age.

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To elucidate details of hormonal regulation mechanism in rat ventral prostate, synthesis of RNAs that contain polyadenylate sequences, polyribosomal sedimentation profile, ribosomal capacity of ³H-Met-tRNA binding, ribosomal initiation factor activity and the rate of polypeptide chain elongation were examined in the ventral prostate from control and castrated animals. The following results were obtained; 1) The concentration of RNAs that contain polyadenylate sequences in cytoplasm of castrated rats was markedly decreased, while the content in nuclear fraction was not influenced significantly by castration. 2) Polyribosomes disappeared quite rapidly after castration and were completely restored 48 hr after testosterone administration. 3) Ribosomal binding capacity with ³H-Met-tRNA and ribosomal initiation factor activity were also reduced significantly. Testosterone treatment of castrated animals completely abolished the effect of castration on ribosomal binding capacity with ³H-Met-tRNA and initiation factor activity. 4) A relatively small effect of castration on the relative rate of polypeptide chain elongation in rat ventral prostates was observed. These results may indicate that the regulation of protein synthesis exerted by testosterone in rat ventral prostates is not restricted at the step of the transcription of mRNA.

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A method for the quantitative estimation of the gonadotropin inhibiting material (GIM) in human urine is standardised using the ovarian ascorbic acid depletion test, the results being expressed in terms of and HCG units. A dose-response relationship with GIM is established. The reliability of the assay is demonstrated. Unlike other methods of assay this method is able to express precisely the quantity of GIM present in the urine. Preliminary data on GIM values in normal subjects as well as patients with endocrine disorders are presented.

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Glipizide, a new anti-diabetic agent, in a dose of 5μg/ml stimulated insulin release promptly in the perfused rat pancreas in vitro. The pattern of insulin release was close to that of tolbutamide reported by others and in this experiment. This result suggests that the pharmacological action of glipizide might be similar to that of D 860.

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Long-term total sleep deprivation was applied to male rats using a special cage, in which the rats were continuously forced to move in order to avoid an electric shock through the floor. In comparison with untreated control, three groups of 24-, 48-and 72-hr sleep-deprived rats showed marked weight increases in the adrenals (30.8-47.7%), testes (6.2-15.0%), ventral prostates (59.7-90.7%) and seminal vesicles (34.2-40.1%). It is supposed that either the sleep deprivation per se or stressful conditions accompanied with the treatment caused a hypersecretion of hypophyseal and testicular hormones.

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