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SummaryThe adrenalectomized rat maintained on sodium chloride for 20 days has a subnormal plasma albumin concentration. Pair fed rats exhibit the same low plasma protein concentrations and the same impaired growth rate. In the replacement in part of adrenal cortical function sodium salts appear to permit the adrenalectomized rat to manufacture plasma proteins in a normal manner although appetite is subnormal. Organ weights are not affected.

Ovaries of rats 1, 2, 4, and 18 months old revealed significant delta-5-3-beta-hydroxysteroid dehydrogenase (3beta-OHSD) activity when dehydroepiandrosterone (DHA), pregnenolone, and 16-dehydropregnenolone served as substrates. No enzyme activity was evident in ovaries 4 and 18 months of age when the substrates 17alpha-hydroxypregnenolone, pregnenolone sulfate, and dehydroepiandrosterone sulfate were used. A marked increase in enzyme activity occurred in the granulosae of mature vesicular follicles at 18 months of age. DHA, pregnenolone, and 16-dehydropregnenolone provided similar activities. On the other hand, interstitial enzyme activity exhibited an aging decline with DHA and 16-dehydropregnenolone but increased with pregnenolone. Corpora lutea were less evident in aging ovaries but did exhibit strong 3beta-OHSD activity when DHA was used. Pregnenolone use by corpora lutea was sharply increased in aging rats but no change occurred with 16-dehydropregnenolone. Thus aging was associated with changes in 3beta-OHSD distribution and use of steroid substrate; a change in function is suggested.

SummaryPeripheral serum progesterone levels in rats fed a protein-free diet show a dramatic decrease on day 11 of pregnancy and remain low thereafter. This drop and the resultant abortion can be prevented by concomitant injections of prolactin and estrone in the intact or hypophysectomized animal. The decline in serum progesterone levels at day 11 of pregnancy suggests a defect in placental development and secretion of luteotrophin and that early secretion of adequate amounts of prolactin and ovarian steroids are required for placental formation and function.

Studies were made on the effect of protein-free diet (PFD) feeding and on recovery from PFD feeding on sex organ weight, serum testosterone, pituitary prolactin and pituitary growth hormone content of young (4 months old) and old (18 months old) male rats. After 20 days of protein depletion, the testis weight remained almost the same, but the ratio of testis weight to body weight was higher in the lower age group, demonstrating a greater resistibility to protein deficiency in young rats. The weight of the seminal vesicle and prostate decreased on ingestion of PFD in both age groups, but a more marked increase was shown in refed young rats. Feeding of PFD for 20 days significantly reduced pituitary prolactin, pituitary growth hormone and serum testosterone in both age groups. Refeeding of protein increased these hormones, but a more marked increase was also observed in the younger group. These results seem to support the hypothesis that one of the important characteristics of an aging organism is its reduced capacity to adapt to environmental changes.

Male Long-Evans rats, 4 and 18 months old, were studied for age differences in competence of androgen production. Testes from these animals were incubated in vitro with labeled progesterone. In the older rats, testosterone production was significantly lower than in the young rats. Aging also resulted in a sharp decline in 5α-androstane- 3α,17β-diol production and a concomitant increase in a polar compound tentatively identified as 7α-hydroxytestosterone, but had no effects on the formation of 17α-hydroxyprogesterone, androstenedione and 5α-dihydrotestosterone. Basal levels of serum testosterone were measured in a circadian time course in both 4 and 18 month old rats. Serum testosterone was significantly greater at all times in the younger animals with the exception of 2000 h and of 2400 h, the latter being the nadir for both age groups. Peak levels of serum testosterone were found at 0800 h and 1600 h in the young and at 0800 h and 2000 h in the older animals. Thus, the older rats exhibited reduced testos...

Ovarian fragments from two amphibians, Rana pipiens and Necturus maculosus were incubated with labeled pregnenolone, progesterone, or testosterone. Progesterone could not be identified when pregnenolone was used as precursor; however, 17α-hydroxyprogesterone was identified in incubates of Rana ovaries. Metabolism of added progesterone was similar in the two species, but metabolism of C-19 steroids differed. Rana pipiens ovarian tissue favored reduction to 5β compounds, while Necturus maculosus ovarian tissue favored reduction at the 5α position.

1. 1. Alkaline phosphatase, β-glucuronidase and glycogen were measured in teh oviduct tissues of adult female Natrix sipedon pictiventris throughout the reproductive cycle. 2. 2, Significant changes in all three components occurred which could be correlated with ovarian and oviduct growth. 3. 3. The results are discussed in relation to possible ovarian influences on the oviduct.

Rats were made hypothyroid by feeding .25% thiouracil in a semipurified casein diet to mothers from the first day of pregnancy through lactation. At 15 days of age, concentrations of adrenal and serum corticosterone were comparable in euthyroid and hypothyroid young, suggesting a basal ACTH release. Ether stress, however, failed to elicit an increased synthesis and release of corticosterone in the hypothyroid rat, but was effective in the euthyroid animal. Exogenous ACTH, on the other hand, did induce corticosterone synthesis and release in hypothyroid and euthyroid rats, indicating a functional adrenal gland. Thus, neonatal hypothyroidism appears to influence the hypothalamus. The retarded maturation of this axis may play a role in behavioral deficiencies seen in hypothyroid animals.

VARIOUS clinical syndromes which are diagnosed as due to the hypofunctioning of an endocrine organ frequently necessitate the administration of substitution therapy for considerable periods of time. Certain therapeutic measures involve the injection of extracts containing proteins of heterologous source and in these instances antagonistic factors (antihormones?) may form in the blood stream to negate the action of the injected hormone and perchance to cause anaphylaxis. The majority of investigations on this subject involve the study of experimental animals and recent reviews (Collip, et al., 1; Thomson, et al.,2; Thompson, 5) discuss the matter thoroughly. The present report, however,deals primarily with the clinical aspects of this problem. Clinical use of insulin in diabetics during the past 20 years shows that refractoriness to insulin is rare. Cases of refractoriness to insulin therapy in man have been reported but it is generally thought that this refractoriness is not antihormonic in nature. Howeve...

Animals fed a protein free diet (PFD) without steroid therapy failed to maintain pregnancy. Injection of 0.5 μg oestrone and 6 mg progesterone daily between days 3 and 20 or days 3 and 12 of pregnancy allowed 100% pregnancy maintenance. Restriction of the steroid injection regime to between days 7 and 9 of gestation reduced pregnancy maintenance to 36%. Prolactin (50 IU subcutaneously twice daily) allowed 78% pregnancy maintenance. The evidence suggests that protein deprivation acts rapidly during early pregnancy to reduce hypophysial secretion of the hormones necessary for pregnancy maintenance, specifically prolactin.

THE adrenal hypertrophy which follows the injection of estrogen is well documented. However, recovery of adrenal size and function following estrogen induced stress and the factors which modify the recovery phase have received little attention. Lynch (1952) observed that the adrenal continued to hypertrophy, in rats, for 3 weeks after discontinuing estradiol benzoate and that adrenal weight did not return to normal until 9 weeks after the cessation of treatment. The influence of nutrition on the recovery phase was not studied. Nevertheless, nutritional studies warrant consideration for chronic inanition alone serves as a stress in rats (Quimby, 1948), guinea pigs (D’Angelo et al., 1948) and mice (Boutwell et al., 1948). Furthermore, a high protein diet may increase the response of the pituitary-adrenal system to stress (Ingle et al., 1947; Leathern, 1947; Hay et al. 1948; Moya et al., 1948; Henriques et al., 1949) and an adequate amount of protein is required for a maximal adrenal response to stress (Cons...

CPIANGES in adrenal size (Selye, 1936; Tepperman, Engel and Long, 1942; Chan, 1950) sudanophilic lipid (Selye, 1936; Zwemer, 1936; Knouff, Brown and Schneider, 1941; Dosne and Dalton, 1941; Darrow and Sarason, 1944) cholesterol (Popjack, 1944; Levin, 1945; Ludewig and Chanutin, 1947; Fortier et al, 1950) and ascorbic acid (Sayers and Sayers, 1948) are induced by stress. In this regard, chronic infections may serve as a continuous stress and thus influence the functional activity of the adrenal cortex. In general, adrenal hypertrophy and a loss in lipid accompanies prolonged infections (Deanesly, 1931; Menten and Smith, 1936). More recently, Sayers and his co-workers (1944) have shown that infectious diseases will deplete the adrenal gland of cholesterol and may favor adrenal exhaustion (Long, 1947; Pinchot, Close and Long, 1949). Attention was drawn to the possible involvement of the adrenal gland in the death of Golden hamsters {Mesocricetus auratus) infected with Leishmania donovani as many hamsters exh...

FOR many years the acetate of desoxycorticosterone (DCA) has occupied a preeminent position as the 11-desoxycorticoid of widest use. The compound is generally administered in oil solution and the effect of a single injection is of moderate duration. A quick-acting, water-soluble desoxycorticosterone—desoxycorticosterone glucoside—has been prepared; it is very effective in reviving dogs from crises of adrenal insufficiency (Meier, Gysel and Muller, 1944; Swingle, Perlmutt, Seay and Collins, 1952). We report here obervations on esters of desoxycorticosterone which, on the other hand, are markedly longer acting than DCA. It has been known for some time that esters of desoxycorticosterone other than its acetate had more prolonged activity and this was notably true of the benzoate and palmitate (Miescher, Fischer and Tschopp, 1938). More recently the trimethylacetate of desoxycorticosterone has been prepared by Wieland, Heer, Schmidlin and Miescher (1951). The preliminary results of these authors indicated a l...

THE PRESENCE of antigonadotropic substances in human sera following treatment with equine gonadotropin (pregnant mare serum) has been demonstrated in men and women (1, 2). Tests for the presence of these antigonadotropic substances in human sera indicated that they were initially present about 10 weeks after treatment was instituted and increased in titer with continued therapy. Furthermore, these antigonadotropic substances remained in the serum for months after cessation of treatment. Therefore, if the equine gonadotropic activity is nullified by the body as is indicated by our tests in mice and rats, then continued treatment with the hormone would be essentially valueless. Whether the antigonadotropic evocating factor is the actual hormone or the nonhormonal material in the extract remains be determined with crystalline preparations. However, extracts of different degrees of purity have been investigated and Gordon (3) has recently shown in tests in rabbits and rats, using 4 pregnant mare serum prepara...

SummaryOvarian cysts were experimentally induced by injecting hypothyroid rats with human chorionic gonadotropin. Cystic ovarian tissue synthesized in vitro a large quantity of 20α-hydroxypregn-4-en-3-one but estrogen synthesis was low.

STUDIES on the rat testis have included weight changes, spermatogenic activity and histochemical investigations. However, little attention has been directed toward the biochemical estimation of testis glycogen, lipid and nitrogen. The rat testis consists of approximately 85% water and 15% solids. The testis solids of adult rats are 65–70% protein (Addis, Poo and Lew, 1936; Aschkenasy and Dray, 1953; Leathern and Glasser, 1953) and approximately 30% lipid (Leathern and Wolf, 1955). Fresh testis tissue has yielded detectable glycogen (Leonard, 1952; Wolf, 1954). Testis protein is decreased by hypophysectomy and estrogen administration (Leathern and Glasser, 1953; Leathern, 1954; Greenberg and Leathern, 1954). However, fasting or feeding a protein free diet for 30 days does not deplete the adult rat testis of protein (Addis, Poo and Lew, 1936; Leathern, 1954). Nevertheless, maturation of the reproductive system is influenced by nutrition. In view of the paucity of information on the major components of the i...

IT HAS BEEN SHOWN that an important relationship exists between the adrenal cortex and the serum protein concentrations. Administration of adrenal cortical extract to hypophysectomized rats will largely prevent the fall in serum albumin usually evident after removal of this gland but does not prevent the rise in globulin concentration. Administration of stilbestrol to stimulate the adrenal cortex of normal rats causes a significant rise in serum albumin concentration (Levin and Leathern, 1942). Moreover, adrenalectomy in cats and dogs where a high degree of adrenal cortical insufficiency is readily obtained is followed by a decrease in serum albumin and a rise in globulin which can be corrected by adequate amounts of adrenal cortical extracts (Levin, Leathern and Crafts, 1942; Hartman, Lewis, Thatcher and Street, 1942). Furthermore, White and Dougherty (1945) have shown that injection of adrenal cortical extract is quickly followed by a rise in serum globulin in rabbits.

SummaryTestis δ5-3β-hydroxy steroid dehydrogenase activity and protein content were determined in rats 4–24 mo of age. Activity of the enzyme per milligram of protein declined between 12 and 18 mo of age and remained depressed through 24 mo of age. Total testis enzyme activity was maximal at 12 mo of age. Chorionic gonadotropin increased testis 3β-OHSD activity significantly in 2-yr-old rats.

Immature rat ovarian dehydrogenase activity was studied during corpus luteum regression following withdrawal of prior pregnant mare serum gonadotrophin. Glucose-6-phosphate dehydrogenase activity declined to nontreatment levels whereas 6-phosphogluconate, malate, and isocitrate dehydrogenase dehydrogenases exhibited a partial return to normal. Adrenalectomy prior to PMS withdrawal enhanced the decline in MAD while sharply elevating G6PD and 20alpha-hydroxysteroid dehydrogenase. Corticosterone and progesterone prevented the G6PD changes induced by adrenalectomy and moderated the rise in 20alpha-OHSD. Adrenalectomy appears to enhance the process of luteolysis.

SummaryPregnenolone is capable of maintaining spermatogenesis for at least 20 days following hypophysectomy. However, this steroid does not influence the seminal vesicles, since the loss in seminal vesicle weight simulates that observed in the hypophysectomized control. Pregnenolone therefore appears to be gametogenic in action.A single injection (10 mg) of pregnenolone did not influence uterine weight or the adrenal X-zone of the spayed mouse.Pregneninolone, which has been shown to exhibit androgenic activity, failed to maintain spermatogenesis in the hypophysectomized rat.

SummaryIn castrated-hypophysectomized rats estrogen did not stimulate mammary duct growth. The injection of lactogenic hormone caused a thickening of the duct system and in combination with estrogen it induced mammary duct growth similar to that seen in intact rats following estrogen injections.

SummaryOvaries and adrenals of both Natrix sipedon pictiventris and Coluber c. constrictor synthesized progesterone in vitro from ∗H-16-pregnenolone. Progesterone synthesis by the ovaries and adrenals of Natrix was 3 times that of Coluber.

SummaryWhen traumatization of one horn of the uterus of progesterone-treated ovariectomized mice was delayed until 4 days after the traumatization of the contralateral horn, deciduomata developed only in the horn first stimulated. On the other hand, deciduomata developed in both horns when the uterus was traumatized bilaterally during a single operation. Since the deciduomal reaction is the experimental equivalent of the maternal placenta, these observations suggest that the maternal placenta plays an important role in the desensitization of the pregnant uterus to decidua formation. This is an important factor in the prevention of superfetation.

SummaryA comparison of 20α-hydroxypregn-4-en-3-one and corticosterone reveals that their fluorescence properties are similar in concentrated sulphuric acid. Since rodent ovaries secrete 20α-hydroxypregn-4-en-3-one, this steroid may interfere with the assay of corticosterone by fluorimetric techniques; however, interference may be reduced by the use of a petroleum ether wash. It is suggested that a fluorescence method may be used as a sensitive assay for 20α-hydroxypregn-4-en-3-one.

SummaryThe effect of a high protein diet (78% casein or lactalbumin) was studied in male rats. The rate of body weight increase was retarded over a 3-week period by a 78% lactalbumin diet in young and adult rats. A modest increase in adrenal weight was observed but no indication of increased! functional activity was suggested by alterations in plasma albumin or globulin concentrations since the plasma protein levels remained unchanged. Non-protein nitrogen was elevated by the excess dietary protein. Thyroid, pituitary, testis and seminal vesicle weights remained normal but kidney and liver weights were increased. Liver protein was increased: in young rats fed the high lactalbumin diet.