Functional changes of the pituitary thyroid system in healthy aged subjects ranging from 60 to 94 year olds were compared with those of healthy adults from 25 to 35 year olds.
As a result, significant decreases in triiodothyronine resin sponge uptake rate and free thyroxine index (FT₄I) were observed in the aged group, while no significant change in the thyroxine levels was indicated. TSH levels in serum tended to be elevated in the aged, although no negative correlation between TSH levels and FT₄I was seen. A significant difference in TSH responses between 100μg and 300μg doses of TRF was observed in the adult control, on the other hand, no difference was seen in the aged group. A comparison of TSH responses to relatively small doses of TRF (100μg) was made between the adult control and the aged, and a significantly higher responsiveness was observed in the aged group. It is postulated that a higher TSH response to relatively smaller doses of TRF is characteristic in the aged probably due to a reflection of a latent hypothyroid state.

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The inhibitory effect of estriol on the development of experimental osteoporosis produced by low calcium diet was studied through the analysis of calcium content and amino acid composition of insoluble collagen of the femurs and tibiae. A marked decrease in the calcium content of bones was significantly prevented by the simultaneous daily oral administration of 40μg estriol. Although lysine, hydroxylysine and sum of lysine and hydroxylysine in the insoluble collagen of bones in low calcium-fed rats were increased when compared with those in control, these values were decreased by the simultaneous administration of estriol, compared with those in low calcium-fed rats. The simultaneous daily oral administration of 300μg estriol to low calcium-fed rats showed no statistical difference against control, in the sum of lysine and hydroxylysine. The changes of these amino acids suggest some alteration of crosslinks in collagen.
The biochemical structure of collagen has been elucidated recently. However, the mechanism of calcification in relation to the minute changes in collagen structure is not yet clear. The effect of estriol on collagen and the protecting effect of estriol against the loss of bone mineral suggest the relation of molecular structure of collagen with calcification.

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Relationship between serum TSH response to TRH and serum thyroid hormone levels was studied in 8 patients with single hyperfunctioning nodule of thyroid. The results were variable. No or low response to 500μg TRH was observed in 6 subjects, 3 of whom were associated with evevated T₄ and T₃, one with normal T₄ and elevated T₃ and two with normal T₄ and T₃. Normal response was shown in other 2 subjects with normal T₄ and T₃. Following administration of 2, 000μg TRH to 3 subjects with absence of response to 500μg TRH, 2 subjects with elevated T₄ and T₃ showed no response, but one with normal T₄ and T₃ showed low but definite response. After removal of the nodule, TSH response to TRH was increased in 3 subjects. Two of them was associated with decreased T₄ and T₃ but another one showed negligible changes in T₄ and T₃. These findings may indicate that responsiveness of TSH to TRH in these patients is not solely dependent on circulating thyroid hormone levels.

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The activities of the synthetic cyclized tetradecapeptide (GIF, Somatostatin) were investigated in isolated rat pituitaries in vitro and in rats treated with nembutal under ether anesthesia or with chlorpromazine (CPZ) under urethane anesthesia. It was found in in vitro study that 250nM or larger doses of the cyclized GIF partially but significantly inhibited GH release and that the incorporation of ¹⁴C-leucine into the pituitary GH was also significantly reduced by 25nM of the cyclized, whose dose neither affected the release of synthesized GH into the medium nor suppressed the release of immunoreactive GH. On the other hand, a single intravenous (iv) injection of 100μg of the cyclized GIF did not affect the basal levels of both serum GH and prolactin. The raised levels of serum GH induced by nembutal (2.5mg/100g body weight, iv) were completely suppressed by a concomitant iv administration of 100μg of GIF but not 10μg. CPZ (500μg/100g body weight, iv)-induced serum GH rise was also completely inhibited by 100μg of GIF, whose dose did not suppress CPZ-induced serum prolactin rise. In another study, 5μg of GIF was given by a single iv injection with nembutal and 10μg of GIF was immediately infused for 30min. No increase in serum GH levels was observed in any rat during the infusion, but the levels were abruptly elevated in 7 out of 9 rats 15min after the cessation of the infusion. The similar ‘rebound’was noticed in 4 out of 9 rats when the dose of GIF was reduced to one fifth. The levels of serum GH were also abruptly raised at the same interval in 3 out of 7 rats given iv both CPZ (50μg/100g body weight) and GIF, but not in any rat treated with GIF alone.

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Acute effect of synthetic LH-RH upon LH and FSH-gonadotrophs in prepuberally ovariectomized female rats 3days after a short-term estrogen-progesterone treatment was investigated electron microscopically along with the radioimmunoassay of LH and FSH. Thirty days after ovariectomy, so-called central LH-gonadotrophs dispersed, but the castration cells which might originate from FSH-gonadotrophs accumulated in the central area of the gland; most of peripheral LH-gonadotrophs became slightly affected, although there was a possibility that some of them took an appearance of castration cells. Secretory granules were considerably driven out of castration cells filled with dilated cisternae. Following the estrrgen-progesterone pretreatment, some peripheral castration cells quickly dispersed and normal ovoid LH-gonadotrophs filled with secretory granules appeared again. Central castration cells were not, however, recovered from their cell hypertrophy, but from the reduction in size of cisternae. Steroid pretreatment thus could enough prevent the release of granules from the castration cells. Those rats were i. v. injected with LH-RH 100ng/ml/rat 33 days after the castration. Serum LH was highest after 5 and 10min, but mean pituitary LH content was unchanged through the testing periods except for diminution at 5 and 180min. Serum FSH concentration rose slightly, but mean pituitary FSH content showed no change except for diminution at 5 and 180min. Morphologically, LH-RH temporally and slightly deprived peripheral LH-cells of the secretory granules within 5min and made central LHcells visible again within 5 and 10 min through their granulation. On the other hand, LH-RH exerted the primary effect upon FSH-castration cells to drive out transiently but efficaciously the secretory granules within 5, 10min or later, along with the more profound contraction of cisternae. The interval of 5min may be assumed as the “discharging phase” of LH-gonadotrophs, and the interval between 5 and 10min as “primary short-term discharging phase” of FSH-gonadotrophs. Subsequently, both kinds of gonadotrophs began to reproduce their secretory granules. The interval between 10 and 30min may be called “synthesizing phase” of FSH-gonadotrophs; the interval up to 60 min may represent the “storage phase” taking the form of FSH-castration cells. LH-RH exerted the secondary, mild but prolonged effect of granular discharge upon FSH-castration cells within 180min causing a transformation into the typical castration cell with numerous open cisternae. Signet-ring cells were, however, scarcelly changed in response to this dose of releasing hormone. It was concluded that LH-RH would act not only slightly upon LH-gonadotrophs but also biphasically upon FSH-gonadotrophs to discharge the secretory granules which may be associated with LH secretion both in acute and subacute periods. Evidences for the intrinsic capacity of so-called FSH-gonadotrophs to secrete LH in contradiction to their name are now available. It is therefore quite hard to identify certainly LH-gonadotroph with FSH-gonadotroph on the basis of their morphological criteria.

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HCG subunits were isolated from hCG by chromatography on DEAE Sephadex A-50. Iodination of hCG by the enzymatic iodination method resulted in a preparation labeled almost exclusively on the α-subunits of hCG, and masking of tyrosine residues in the β-portion when bound to the α-portion of hCG molecule was interpreted.
Antisera of the hCG subunits enabled radioimmunoassay of those subunits. Sera obtained from pregnant women were radioimmunoassayed for hCG, hCG-α and hCG-β in respective homologous radioimmunoassay systems. Real amounts of those hormones were calculated by subtracting the interferes of non-homologous hormones in the homologous assays. Absolute amounts of hCG reached its peak (several microgrammes per ml) in the first trimester, then decreased and continued the values less than 1.5 microgrammes per ml thereafter. Surprisingly the amounts of hCG-α in sera increased in the former half, reaching several hundreds nanogrammes per ml in the latter half of pregnancy, while the amounts of hCG-β were ranged in less than 100 nanogrammes per ml. The significance of immunoreactive hCG-α during pregnancy was speculated.

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Rat adrenal contains dialyzable and non-dialyzable corticosterone. Total dialyzable corticosterone increased remarkably 20 and 30 min after a single subcutaneous injection of ACTH (1U./rat), while non-dialyzable corticosterone decreased 20min after ACTH followed by an increase 30min later. The increase of dialyzable and the decrease of non-dialyzable corticosterone were most pronounced in the cytosol fraction. Similar change in the contents of both types of corticosterone was also seen in the nuclear fraction after ACTH. In mitochondrial and microsomal fraction, definite increase of both types of corticosterone followed ACTH administration.
No [³H] corticosterone binding in vitro to adrenal cytosol was detected, while it became detectable after the cytosol was dialyzed. Degree in the binding increased as the dialysis continued. Similar finding was obtained with the solubilized component of subcellular particle fractions by sonication. On the other hand, nuclear fraction, after exclusion of soluble component by sonication, associated with [³H]-corticosterone definitely although the fraction was not dialyzed. When adrenal homogenate was incubated with [3H] corticosterone in Visking dialysis tubing at 37°C, corticosterone in dialyzates maintained constant specific radioactivity from 5 to 40min after the begining of incubation. The specific radioactivity in successive 21 hr-incubation at 3°C tended to decrease gradually with incubation time. The adrenal homogenate, after the termination of incubation, had significantly lower specific radioactivity than those of the dialyzates. The incubation of adrenals with [3H] cholesterol solubilized in rat serum indicated gradual decrease of specific radioactivity of medium corticosterone along with the incubation time, suggesting a preferential release of newly synthesized corticosterone from the exogenous precursor.
In addition to free corticosterone, rat adrenal contains corticosterone bound to organelles. A significant part of dialyzable or free corticosterone might have originated from a loosely bound form of corticosterone, while nondialyzable corticosterone appears to be tightly bound form. Transformation between bound and free form might play a role for secretion mechanism of adrenal corticosterone. The binding of corticosterone to macromolecules in the adrenal subcellular fractions would be related not only to storage but also to secretion mechanism of adrenal corticosterone.

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Intravenous preadministration of somatostatin (Growth Hormone Inhibiting Factor: GIF) inhibited TRH-induced TSH release in rats anesthesized by pentobarbitulate. There was dose dependent negative interaction between the inhibitory effect of GIF and releasing effect of TRH. TSH releasing effect of small dose of TRH was inhibited completely by preadministration of GIF, while large dose of TRH overcame the inhibitory effect of GIF. The mechanism responsible for inhibitory effect of GIF on TRH-induced release was discussed.

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Two-day-old female rats were given bilateral implants of small pellets each containing 5μg MER-25 in bone wax in the medial preoptic to ventromedial areas of the hypothalamus. At the same time, the rats received a single subcutaneous injection of 50μg testosterone propionate. Ovaries of the rats were examined by laparotomy for the presence of corpora lutea at 50 days of age. At 100 days, ovaries were removed and studied histologically. Sterilizing action of testosterone propionate was not inhibited by intrahypothalamic implants of MER-25, at least the present experimental conditions.

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Pituitary G-6-PDH activity was increased when pituitary weight is augmented by the use of a low iodine diet or treatment with methiocil for a few weeks. In contrast, pituitary enzyme activity was decreased by T₄ treatment.
The increased enzyme activity may be due to the increased weight of pituitary as a result of prolonged elevation of TSH secretion. However, the augmentation of pituitary weight was less pronounced following treatment with methiocil or low iodine in comparison with the increase in thyroid weight. Therefore, the augmentation of total enzyme activity in the pituitary was less than that in the thyroid. This experiment showed that pituitary G-6-PDH activity is increased in the pituitary gland when a continuous increase in TSH secretion occurs.

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Effects of ACTH and dexamethasone administration on the half-lives of protein and RNA of the subcellular fractions from rat adrenal glands were examined. A significant increase in the half-lives of protein and RNA in ACTH-treated animals and the rate of half-life elongation was apparently correlated with the degree of hypertrophy of the tissue. While, administration of dexamethasone or cortisol induced an acceleration of protein and RNA degradation and also in this case, the rate of degradation seemed to be correlated with the degree of tissue atrophy. From these results, it was concluded that degradation process of protein and RNA may participate the role in hypertrophy and atrophy of the tissue.

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