Showing papers on "Testosterone published in 1968"

Selective retention of dihydrotestosterone by prostatic nuclei

Abstract: MUCH attention is being given to the effect of gonadal hormones on various biochemical events in the cell nuclei of the target tissues1–7. It is not known whether steroids act directly at nuclear sites; oestradiol-17β seems to associate with nuclear components without alteration of the oestrogen molecule8,9. Ventral prostate can retain androgens to a somewhat greater extent than the blood10,11, but studying the method of androgen retention is complicated by the rapid and multiple transformations of androgens injected into the experimental animals10–12. Consequently, we have asked two simple questions: (1) which metabolite(s) of testosterone can associate with isolated prostatic nuclei; and (2) is such association selective ? The results reported in this paper suggest to us that nuclear chromatin of prostate, but not other tissues which are insensitive to androgen, contains an androgen receptor which can selectively retain dihydrotestosterone (DHT, 5α-androstane-17β-ol-3-one)—the most potent endogenous androgen for the growth of ventral prostate of rat13,14.

Metabolism of testosterone and action of metabolites on prostate glands grown in organ culture.

Abstract: TESTOSTERONE metabolites are found in the prostate gland in vivo1,2 and preliminary experiments, briefly reported3, indicate that prostatic tissue grown in vitro metabolizes the hormone. The action of testosterone could be caused directly by the hormone, or indirectly through its transformation into metabolites, for example, through tran-hydrogenation4, or to metabolites themselves5.

Studies of Testosterone Binding Globulin

Abstract: Normal and pregnancy plasma contains testosterone binding substances. Binding activity is essentially abolished by heating plasma to 60 C or lowering pH to <5. Albumin has low affinity but high capacity for testosterone while testosterone binding of whole plasma or albumin-free plasma has high affinity and relatively low capacity. Studies of pregnancy plasma with 3H-testosterone using Sephadex G-200 chromatography, immunoelectrophoresis and plasma electrophoresis on paper, indicate that the high affinity binding substance has characteristics of a beta globulin. Testosterone binding globulin (TBG) activity tested by dextran coated charcoal particle adsorption of free labeled testosterone is increased in pregnancy or estrogen administration and appears slightly more active in normal female than male plasma Studies based upon displacement of 3H-testosterone from pregnancy plasma TBG indicate a high degree of stereospecificity for binding which differs completely from the characteristics of cortisol ...

Aggression in Adult Mice: Modification by Neonatal Injections of Gonadal Hormones

Abstract: Incidence of spontaneous aggression in adult male mice given a single injection of estradiol benzoate (0.4 milligram) when they were 3 days old was less than that of controls injected with oil. Aggressiveness was increased among adult females injected with either estradiol or testosterone propionate (1 milligram) at the same age. The increased aggressiveness noted among females given androgen was further documented during subsequent mating tests, when these females often attacked, wounded, and, in one case, killed naive males.

Regulation of Human Gonadotropins. III. Luteinizing Hormone and Follicle Stimulating Hormone in Sera from Adult Males1

Abstract: Radioimmunoassays for follicle stimulating hormone (FSH) and luteinizing hormone (LH) were used to determine the concentrations of these gonadotropins in sera from healthy men. No evidence of diurnal or other rhythmic variations in serum concentrations was found in samples obtained daily, 3 times a day, or hourly. Treatment of 3 subjects with 1.5 mg of ethinyl estradiol/day for 2–3 days resulted in a consistent fall in serum concentrations of both FSH and LH. Treatment of 3 subjects with 25 mg of testosterone propionate each day for 3 days resulted in a consistent fall in serum concentrations of LH. Treatment of 4 subjects with 200 mg of clomiphene citrate daily for 3 days resulted in a rise in serum concentrations of both FSH and LH.

Suppression of Testosterone and Androstenedione Production Rates with Dexamethasone in Women with Idiopathic Hirsutism and Polycystic Ovaries

Abstract: Testosterone and androstenedione plasma levels were measured in 7 normal women and 22 hirsute women with either idiopathic hirsutism (IH) or polycystic ovaries (PCO). During dexamethasone administration, plasma testosterone decreased 25% in normal subjects and 40–50% in the patients with IH and PCO. Plasma androstenedione levels were suppressed 40–55% in the normal and hirsute women. The mean testosterone metabolic clearance rate for 8 hirsute women increased 10 % during dexamethasone administration but there was no significant change in the androstpnedione metabolic clearance. Thus, the decrease in blood androgen levels produced by glucocorticoid was a consequence of decreased androgen production. These studies indicate further that a gland which is suppressed by dexamethasone is responsible for a significant fraction of the excess androgen production in women with either IH or PCO.

Site of Action of Trophic Hormones Upon the Biosynthetic Pathways to Steroid Hormones

Abstract: Slices of bovine adrenal cortex, bovine corpora lutea and rabbit testes were incubated with 20α-hydroxycholesterol-7α-3H or with cholesterol-7α-3H with and without the trophic hormones ACTH (adrenal cortex) or ICSH (corpora lutea or testes) added in vitro. In confirmation of previous findings, the trophic hormones increased the conversion of cholesterol-3H to cortisol-3H (adrenal cortex), progesterone-3H (corpora lutea) and testosterone-3H (testes). On the other hand, the trophic hormones produced a slight decrease in the conversion of 20α-hydroxycholesterol-3H to the same steroid hormones. In the case of the corpus luteum this decrease was less when incubation was continued for longer times, but under none of the conditions tested in any of the 3 tissues was the conversion of 20α-hydroxycholesterol-7α-3H to the steroid hormones increased in the presence of the trophic hormones. In the case of the testis similar results were observed 1 hr after a single intravenous injection of ICSH. These findings were m...

Carcinoma of prostate: response of plasma luteinizing hormone and testosterone to oestrogen therapy.

Abstract: Oestrogen therapy has become well established as a method of treatment of local and metastatic prostatic carcinoma, following the pioneering investigations ot Huggins and his co-workers (1939, 1940, 1941). In a large majority of affected patients prostatic tumours and their metastases are hormone-sensitive and endocrine therapy has been undertaken with the purpose of altering the hormonal milieu and, specifically, of lowering androgen levels. Orchidectomy and/or the administration of oestrogens have become cornerstones of treatment, but relatively little is known of their effects on the secretion of pituitary gonadotrophins and of testosterone, the major physiologically active androgen in man. Furthermore, the results of hypophysectomy for prostate cancer, especially in patients who have relapsed after oestrogen and orchidectomy, have been encouraging enough to warrant further exploration of this procedure, particularly at an earlier stage of the disease. The following studies were undertaken, firstly to gain information about the effects of oestrogen treatment specifically on testosterone and luteinizing hormone levels in patients with prostatic cancer, and, secondly, to provide a basis for comparison of the effects of this treatment with those of hypophysectomy done as the initial procedure for metastatic disease.

Inactivation of the Biological Effects of Exogenous and Endogenous Estrogens by Antibodies to 17β-Estradiol

Abstract: Ewes, immunized with conjugates of 17β-estradiol hemisuccinate coupled to bovine serum albumin, produce antisera capable of neutralizing the hormone in vitro and in vivo. The antibodies inhibited the biological effects produced by estradiol administered to immature or mature ovariectomized rats and mice. Furthermore, they prevented uterine weight increases, endometrial stimulation and vaginal cornification due to endogenous estrogens following treatment with human chorionic gonadotropin. Pretreatment of intact animals with antisera inhibited the uptake by uteri, pituitaries and ovaries of tritiated estradiol administered subcutaneously.The antibodies did not inhibit the uterine stimulation caused by administration of diethylstilbestrol. Antibodies to estradiol did not counteract androgenic effects upon accessory sex organs produced by testosterone administered to immature male rats. Nor did antibodies elicited by testosterone-protein conjugates alter the effects of 17β-estradiol in immature rats. Contrary...

Protection against the neural organizing effect of exogenous androgen in the neonatal female rat.

Abstract: The injection of 30 Mg testosterone propionate to the 5-day-old female induces a high incidence of sterility (IS) which is evident at puberty. Simultaneous injection of 10 μg reserpine, 500 μg chlorpromazine, 2500 μg progesterone, 1000 μg desoxycorticosterone acetate, or 1500 μg pregnanedione markedly reduces the IS during the immediate postpubertal period. This protection is not complete, however, as the IS approaches control levels by 90 days of age. In contrast, pentobarbital or phenobarbital affords the 5-day-old female marked protection against the effect of androgen and only ¼ of the androgenbarbiturate injected females are anovulatory at 90 days of age. The protective effect of pentobarbital is eliminated by simultaneous injection of Metrazol. Depression of neural activity is a common feature following injection of these effective agents, and it may be that this capacity underlies their protective action. (Endocrinology 82: 1005, 1968)

Concentration of androgens in systemic plasma of rats, guinea pigs, salamanders and pigeons.

Abstract: The concentrations of androstenedione, testosterone and dehydroepiandrosterone have been measured in systemic plasma of adult male specimens of domesticated rats, guinea pigs and pigeons and the salamander Necturus. Values for normal human subjects are given for comparison. Striking differences were observed in testosterone concentration among the variousspecies. Several interpretations of this finding are discussed. The androgen content of plasma of sexually mature rats was compared with that of a few pools of plasma from immature animals. The data indicate that the testosterone/androstenedione ratio increases at puberty in the rat. {Endocrinology 82: 115, 1968)

Plasma Androgens in Patients with the Polycystic Ovary Syndrome1

Abstract: Eight patients with the polycystic ovary syndrome (PCO) and hirsutism were studied. Diagnosis was made on the basis of the clinical picture and culdoscopic observation of the ovaries and/or ovarian biopsy. The mean plasma testosterone concentration was 210 mμg and plasma androstenedione 380 mμg/100 ml by double isotope derivative methods using 35S thiosemicarbazide. These values are elevated many times over normal values obtained with these methods. One case, despite histological evidence of polycystic ovaries, had normal plasma androgen values. The metabolic clearance rate (mean 2060 liters/day) and conversion ratio (mean 18.5%) of androstenedione to testosterone in 6 patients studied were normal. This suggests that the over-all metabolism of the major androgen precursor and its peripheral conversion to plasma testosterone is normal. The c 1 ulated mean blood production rate of androstenedione in these patients was 7.8 mg/day. Only ⅓ of plasma testosterone in the PCO syndrome is derived from per...

Effect of Experimental Bilateral Cryptorchidism on Testicular Enzymes Related to Androgen Formation

Abstract: When rat testes were surgically forced to remain in the abdomen for a month, weight of testicular glands was strongly reduced. By histological examination of these testes, interstitial cells were not apparently influenced, but seminiferous tubules containing Sertoli cells showed remarkable atrophy. On the other hand, as weights of seminal vesicles and prostates were found significantly reduced by the experimental bilateral cryptorchidism, the suppression of in vivo androgen production and its secretion in the abdominal testis was suggested. Androgen production from pregnenolone in vitro by the testicular homogenates of cryptorchid rats was found lower than from testes in the scrotum. The activity of Δ5-3β-hydroxysteroid dehydrogenase in the microsomal fraction on the basis of mg protein was reduced to 40% of the activity of the intact testes on the 31st day after the operation and its activity per organ was accordingly further reduced to 16% of the intact testes, indicating that this enzyme activity or it...

The “Puberty” of the Rat Liver. II. Permanent Changes in Steroid Metabolizing Enzymes After Treatment with a Single Injection of Testosterone Propionate at Birth

Abstract: Rats of both sexes were spayed and injected with either 50 or 500 μg of testosterone propionate (TP) on their first day of life or later. Four to 5 months afterward the animals were sacrificed. Liver homogenates or microsomes were incubated with tritium labeled cortisol, tetrahydrocortisol, progesterone and testosterone. Spayed female rats treated with 500 μg or even with 50 μg TP on their first day of life as well as with 500 μg TP on the 6th day developed and maintained during adult life a pattern of steroid metabolism characteristic of male adult animals: the Δ4-3-keto reduction in crude liver homogenate to allo-tetrahydrocortisol and the Δ4-5α-reduction in liver microsomes to allodihydrotestosterone and -progesterone had significantly decreased as compared with spayed control animals. On the other hand, the reduction of cortisol to 3β and 20β-hydroxy metabolites as well as the 20-keto reduction of tetrahydrocortisol to β-cortol had been increased. When female rats castrated in neonatal life were treat...

Androgen-dependent salivary gland protease in the rat.

Abstract: Total alkaline protease activity, 2 different trypsin-like proteases and cathepsin B activity were separately analyzed in the submandibular glands of the rat. One of the trypsinlike enzymes was found to be testosterone induced and responsible for the increased alkaline proteolytic activity in the salivary gland extracts of the adult male rats. The enzyme has recently been described in detail: its pH optimum is pH 8.2, lima bean inhibits its activity completely and Trasylol and CuCl2 very effectively. The trivial name glandulain is used for the enzyme. Androgen dependency was demonstrated in a series of prepuberal rats, where the sexual development was followed by estimating the relative volume of the steroid-producing cells in the testis or the appearance of corpora lutea in the ovary. In the male submandibular glands the glandulain activity was significantly higher than in the female glands from the 40th day of life onward, which was about 10 days later than the first signs of increased activity of testi...

A Testicular-Interstitial-Cell-Stimulating Gonadotrophin in a Child with Hepatoblastoma and Sexual Precocity

Abstract: A gonadotrophin with testicular interstitial-cell-stimulating activity was detected in extracts of hepatoblastoma and a pulmonary metastasis and in the urine of a 3-yr-old male with isosexual precocity manifested by advanced skeletal maturation (bone age 4 yr), adult urinary testosterone excretion (62 μg/day) and Ley dig cell hyperplasia. The gonadotrophin content of the hepatoblastoma, measured by the ventral prostate weight method in immature, hypophysectomized male rats, was 2.6 IU/g. This gonadotrophin was immunologically similar to the luteinizing principle in the Second International Reference Preparation of Human Menopausal Gonadotrophin (2nd IRP-HMG) in a double-antibody radioimmunoassay employing guinea pig antiserum to human chorionic gonadotrophin (HCG), purified human pituitary luteinizing hormone (LH)-131I as tracer and the 2nd IRP-HMG as standard. The standard curves obtained utilizing the 2nd IRP-HMG, pituitary LH and HCG were parallel in this assay. Extracts of normal liver, of li...

The effects of oestrogens and other steroid hormones on the ultrastructure of the liver of Xenopus laevis Daudin

Abstract: Administration of oestradiol-17β to Xenopus laevis Daudin results in profound modifications of hepatic ultrastructure. In all liver cells there is a considerable proliferation of the granular endoplasmic reticulum and an increase in the electron density of the nucleolus. The amount of stored glycogen is depressed. Injection of pregnant mare serum gonadotrophin causes a similar response in intact females but not in males or ovariectomized females, suggesting an indirect effect of this hormone by stimulation of ovarian oestrogen secretion. Oestradiol benzoate, oestrone and oestriol are also able to effect the described response, though in the last case the changes are less complete. Testosterone propionate, progesterone, and cortisone acetate are inert in this respect.

Effects of estrogen, progesterone, and testosterone on the pituitary and ovary of catfish, Heteropneustes fossilis (Bloch).

Abstract: Estradiol benzoate (EB), testosterone propionate (TP) and progesterone have been administered orally over 45 days during the late preparatory period to intact female catfish showing ovarian recrudescence. EB or TP treatment brings about a reduction in the size and number of basophils in the pituitary, and inhibition of vitellogenesis in the ovaries. Progesterone administration causes partial ovarian regression without significantly altering pituitary cytology. The sexually dimorphic urogenital papilla which is inconspicuous and nonmuscular in the female is unaffected by hypophysectomy and/or EB treatment. TP induces complete masculinization of the female papilla, whereas progesterone is only marginally effective. EB injections over 15 days to intact catfish having ovaries containing yolk laden oocytes induce significant reduction in the number of pituitary basophils and extensive follicular atresia in the ovaries. Administration of EB to hypophysectomized catfish inhibits hypertrophy of the granulosa cells surrounding the yolky oocytes and thus delays the impending follicular atresia. The significance of these findings is discussed.

The effects of catabolic and anabolic steroids on amino acid incorporation by skeletal-muscle ribosomes

Abstract: 1. A method is described for the routine isolation of ribosomes from small quantities of skeletal muscle that have been homogenized with the Ultra-Turrax tissue disintegrator. 2. Ribosomes prepared by this method from rats receiving triamcinolone acetonide or rabbits receiving cortisone acetate show a marked fall in their ability to incorporate amino acids when compared with ribosomes from control animals. 3. This fall in activity can be partially prevented in rats by pretreating the animals with an anabolic steroid, steroid 36644-Ba. 4. Testosterone (5mg./kg.) administered to rabbits in conjunction with cortisone acetate is not effective in maintaining ribosomal activity. However, steroid 36644-Ba at one-tenth of an equiandrogenic dose (0·05mg./kg.) is extremely effective. 5. The results with ribosomes isolated from rabbits support the concept that steroid 36644-Ba and possibly all anabolic steroids have an ability to counteract the catabolic action of corticosteroids that is greater than their androgenic activity would suggest.

Pineal gland: Influence on gonads of male rats treated with androgen three days after birth

Abstract: Either blinding or the injection of 1 milligram of testosterone propionate into male Sprague-Dawley rats, 3 days old, results in testes and accessory organs (seminal vesicles and coagulating glands) that are smaller than normal when the rats are 72 days old. The response to blinding is prevented by removal of the pineal gland, whereas the response to treatment with testosterone is unaffected by pinealectomy. Combination of the two treatments in 3-day- old rats causes testes to be less than one-third their normal size at 72 days of age; pinealectomy in these rats permits the reproductive organs to grow to the same size as those in the androgen-treated animals.

Urinary testosterone response to 72-hr. avoidance sessions in the monkey.

Abstract: Urinary testosterone levels show a biphasic response in association with 72hr. avoidance sessions in the monkey, characterized by an initial decline during avoidance followed by a rebound elevation during the recovery period. The duration of the two response phases, the primary lowering and the secondary elevation, may vary from one experiment to the next, but the general configuration of the response curve remains the same. Similar testosterone response curves were obtained both with a double-isotope derivative and a gas chromatographic method, although the latter method gave considerably lower absolute values. Preliminary data indicate that urinary epitestosterone levels also change in relation to avoidance in a pattern similar to the testosterone response. While the mean testosterone curve closely resembles that previously described for urinary androsterone, etiocholanolone, and dehydroepiandrosterone levels, some instances were noted in the present experiments in which there was at least transitory dissociation between the urinary excretion of testosterone and its metabolites. Future study will be required to determine whether this dissociation may possibly be related to eovariation in urinary volume responses, to relatively greater adrenal contribution to androgen metabolite excretion in some experiments, or to other factors. Preliminary experience with gas chromatographic analysis of other individual 17-ketosteroid compounds indicates that the 11-oxy-17-ketosteroids (C19O3-17-ketosteroids) may show a different response pattern than do androsterone and other C19O2-17-ketosteroid compounds. The pertinence of this observation to the continued use of total urinary 17-ketosteroid determination is discussed, and the need for further psychoendocrine studies of androgen levels with the use of increasingly refined endocrinological methods is emphasized.

Metabolic control mechanisms in mammalian systems. Hormonal regulation of phosphofructokinase in the rat prostate and seminal vesicles.

Abstract: 1. The hormonal regulation of phosphofructokinase was investigated in the accessory reproductive organs of the orchidectomized rat. 2. Phosphofructokinase activities declined to 51% and 47% in the prostate and 9% and 6% of the normal values in seminal vesicles 4 and 8 weeks after castration respectively. Administration of testosterone (100μg./100g. body wt.) for 3 days reversed substantially the effects of orchidectomy, and phosphofructokinase activity increased to 173% in the prostate and 536% in seminal vesicles as compared with the values of castrated controls. 3. Time-course studies demonstrated that after a single injection of testosterone (5mg./100g. body wt.) phosphofructokinase activity was maximally elevated to 236% in the prostate and 342% in seminal vesicles at 24hr. 4. Dose–response studies revealed that 2·5mg. of testosterone propionate/100g. body wt. was the minimal amount necessary to induce significant increases in enzyme activity in both accessory sex organs; maximal increases were obtained with a dose of 5mg./100g. body wt. 5. The observed enzyme increases induced by testosterone were inhibited by the simultaneous administration of oestradiol-17β, and phosphofructokinase activity in this group of rats remained at 97% in the prostate and 137% of the control values in seminal vesicles. Oestradiol-17β by itself failed to produce any significant effect on enzyme activity in either of these secondary sexual tissues. 6. The nature of the testosterone-induced increases in phosphofructokinase activity was studied by using a variety of inhibitors of RNA and protein synthesis. Cycloheximide, 5-fluorouracil and ethionine largely blocked the androgen-stimulated rise in enzyme activity observed 24hr. after steroid injection. The inhibitory effect of ethionine was completely reversed by the simultaneous administration of methionine. 7. Actinomycin, which is known to inhibit the synthesis of messenger RNA as well as the synthesis of other cellular RNA fractions, when given simultaneously with the hormone, also inhibited the testosterone-induced increases in prostatic and seminal-vesicular phosphofructokinase. However, when the antibiotic was given 6 or 12hr. after injection of the steroid, practically no inhibition of phosphofructokinase induction was obtained. This indicates that, once the enzyme-forming machinery is turned on and allowed to operate for a few hours, actinomycin is incapable of reversing the hormone-induced enzyme responses. 8. The results presented suggest that new RNA and protein synthesis may be involved in the observed androgen-induced increases in phosphofructokinase activity in the prostate and seminal vesicles of the orchidectomized rat.

Effect of testosterone on ribonucleic acid metabolism in the prostate, seminal vesicle, liver and thymus of immature rats.

Abstract: A single injection of 1 mg testosterone stimulated the synthesis of RNA in the ventral prostate, seminal vesicle and liver of immature rats. In contrast, the metabolism of RNA in the thymus was unaltered by treatment with testosterone. The synthesis of RNA at varying times after the injection of androgen was estimated by the injection of 3H-cytidine 30 min before the rats were killed. The specific activity of the RNA from the purified nuclei and the cytoplasm of these organs was increased markedly 2 and 12 hr after the administration of testosterone but decreased toward control levels at 38 hr. The amount of tritium sedimenting with cytoplasmic ribosomal RNA of ventral prostate and liver was increased 2 and 12 hr after the administration of testosterone. In control rats, isotope was incorporated into the soluble RNA fraction within the 30 min following the injection of 3H-cytidine. The amount of RNA per g tissue in seminal vesicle increased slightly at 12 hr and markedly at 38 hr following administration ...