Vesicle Growth Research Articles

Co-ordination between membrane phospholipid synthesis and accelerated biosynthesis of cytoplasmic ribonucleic acid and protein.

1. The rate of synthesis of membrane phospholipid was studied in rat liver and seminal vesicles by following the incorporation of [(32)P]orthophosphate, [(14)C]choline and [(14)C]glycerol. Particular emphasis was laid on the endoplasmic reticulum, which was fractionated into smooth microsomal membranes, heavy rough membranes, light rough membranes and free polyribosomes. 2. Phospholipid labelling patterns suggested a heterogeneity in the synthesis and turnover of the different lipid moieties of smooth and rough endoplasmic membranes. The major phospholipids, phosphatidylcholine and phosphatidylethanolamine, were labelled relatively rapidly with (32)P over a short period of time whereas incorporation of radioisotope into the minor phospholipids, sphingomyelin, lysolecithin and phosphatidylinositol proceeded slowly but over a longer period of time. 3. The incorporation of orotic acid into RNA and labelled amino acids into protein of the four submicrosomal fractions was also studied. 4. Rapid growth of the liver was induced by the administration of growth hormone and tri-iodothyronine to hypophysectomized and thyroidectomized rats and by partial hepatectomy. Growth of seminal vesicles of castrated rats was stimulated with testosterone propionate. 5. The rate of labelling of membrane phospholipids was enhanced in all major subcellular particulate fractions (nuclear, mitochondrial and microsomal) during induced growth. However, it was in the rough endoplasmic reticulum that the accumulation of phospholipids, RNA and protein was most marked. The effect of hormone administration was also to accelerate preferentially the labelling with (32)P of sphingomyelin relative to that of phosphatidylcholine or phosphatidylethanolamine. 6. Time-course analyses showed that, in all four growth systems studied, the enhancement of the rate of membrane phospholipid synthesis coincided with the rather abrupt increase in the synthesis of RNA and protein of the rough endoplasmic reticulum. Growth hormone and tri-iodothyronine administered to hypophysectomized rats had additive effects in all the biosynthetic processes. The latent period of action of each hormone was maintained so that two waves of proliferation of endoplasmic reticulum occurred if the hormones were administered simultaneously. 7. It is concluded that there is some mechanism in the cell that tightly co-ordinates the formation of membranes, especially those of the endoplasmic reticulum, when an increased demand is made for protein synthesis.

Biological properties of 17-ethinyl-7α-methyl-19-nortestosterone (U-13,851)

U-13,851 (17-ethinyl-7α-methyl-19-nortestosterone) exhibited both estrogenic and progestogenic properties in several biological test systems and was found to be 10 to 40 times as potent as norethindrone in comparative assays. U-13,851 prevented conception in rats at 100 μg/day orally and at one-half that dose systemically. This compound was tested in several biological assays to measure various hormonal effects. U-13,851 exhibited estrogenic activity in that it induced vaginal estrus at 20 μg/day rat. Its estrogenic activities were suggested also in the deciduomata assay and in the pregnancy maintenance test. U-13,851 did not exhibit any antiestrogenic potency against estradiol-induced uterine growth. It was active in the endometrial proliferation assay which is an indication of progestational activity. Tested for androgenic activity, it stimulated growth of seminal vesicles and the levator ani but was relatively inactive in stimulating prostate gland growth. Continuous medication suppressed the cyclic changes in vaginal smears of rats; recovery from long term medication was rapid and complete. Adrenal gland weight was unaltered by U-13,851; thymic weights were significantly depressed.

Effect of an adrenal 17alpha-hydroxylase inhibitor on gonad function.

7-Chloro-3,4-dihydro-2-(3-pyridyl)-1 (2H)-napthalenone (Su-10603), a compound known to inhibit particularly 17α-hydroxylation in the adrenal of the dog, was studied for its effects on gonad and adrenal function in rats. Administration to immature animals for 30 days (100-400 mg/kg/day) inhibited growth of seminal vesicles, ventral prostates, levatores ani and uteri without other obvious effects. It was similarly active in adrenalectomized rats. These results are consistent with previous demonstrations that the drug interferes with testosterone synthesis in vitro. The Su-10603 also inhibited the response of immature males but not females to chorionic gonadotropin as judged by weights of sex accessories. It interfered with the normal processes of pregnancy by means as yet undetermined. Unlike the situation in the dog, it was without effect on adrenal morphology or the corticosterone secretion rate in rats.

Metabolic and enzymatic effects of monoamine oxidase inhibitors with and without hydrocortisone on the accessory sex glands of the rat

Monoamine oxidase inhibitors (MAOI), particularly when administered in combination with hydrocortisone acetate, cause considerable inhibition of the growth of the seminal vesicles, dorsolateral prostates and ventral prostates of immature, adolescent and adult male rats. The above combination increases only the concentration of DNA per g tissue in the accessory sex glands, without affecting other metabolites and enzyme systems (RNA, fructose, acid phosphatase and beta-glucuronidase).

Hepatic Metabolism and the Anti-Androgenic Activity of Cyproterone Acetate.

Summary and conclusionsThe effects of splenic vs. subcutaneous depots of pellets of an anti-androgen, cyproterone acetate (Cyp A), were studied in castrate rats receiving daily injections of .1 mg of testosterone pro-pionate per 100 g body weight, Mean loss of weight of pellets was similar in both sites, indicating comparable absorption. Inhibition of growth of seminal vesicles was significantly less with splenic than with subcutaneous depots of Cyp A (P<.05, Exp 1; P<.001, Exp 2). These data provide evidence that (a) this compound does not exert its anti-androgenic effects by increasing the inacti-vation of testosterone propionate in the liver, and that (b) Cyp A can be destroyed in the liver before producing systemic effects as an anti-androgen. The effectiveness of Cyp A as an anti-androgen was shown by a 40% reduction in androgenic response in studies employing a ratio of 2 parts of Cyp A (supplied by pellets) to 1 part of testosterone propionate (supplied in oil).

The influence of neural retina and lens on the development of embryonic lens vesicles in Amblystoma punctatum and Triturus viridescens

AbstractEmbryonic lens vesicles from both species of salamander self‐differentiated into a small lens with fibers when implanted into either the dorsal fin or anterior chamber of the larval eye. Growth of these lenses was very slow in Amblystoma and somewhat faster in Triturus. When implanted into the pupil in place of the extirpated host lens, the embryonic lens vesicles differentiated normally and had a normal rate of growth. Lens regeneration from the host iris in Triturus was frequently inhibited by the implanted lens. A statistical analysis by the method of covariance showed that, in both species, lenses from the implants were largest in the lentectomized eyes, smaller in the vitreous chamber of eyes with intact host lens and smallest in the anterior chamber, host lens present. In Amblystoma, the growth rates, as indicated by the coefficients for linear regression, were significantly different between lenses developing in the absence of the host lens and those growing from implants into either the anterior or vitreous chambers of eyes containing the host lens. In Triturus, a significant difference was observed only between growth rates of lenses in the lentectomized eyes and in the anterior chambers, host lens present or in the dorsal fin. These results show that the neural retina stimulates growth and differentiation of embryonic lens vesicles and that the host lens retards their growth.

Effect of testosterone propionate and growth hormone on growth and chemical composition of muscle and other tissues in hypophysectomized male rats.

The effect of testosterone propionate and growth hormone on the growth of muscle, bone, pelt, viscera and seminal vesicles was studied in hypophysectomized male rats. Testosterone (0.1 mg/day) stimulated growth in the levator ani muscle and seminal vesicles but had no effect on the other tissues studied. Growth hormone (0.1 mg/day) accelerated growth in all tissues except the seminal vesicles. Testosterone did not enhance the growth-promoting effect of growth hormone in any tissue except the levator ani muscle. Growth hormone stimulated deposition of myosin, sarcoplasmic proteins, collagen and alkali-soluble proteins in the thigh muscle of hypophysectomized rats. The composition of the muscle in treated and control hypophysectomized rats was the same as that in normal rats. Growth hormone also increased the collagen, keratin-elastin and globular protein content of the pelt. The effect of growth hormone on the proteins of muscle and pelt was not enhanced by testosterone. Testosterone given alone had no eff...

Lack of inhibitory or excitatory effects of sex hormones on the development of normal methylthiouracil-induced goiter in the rat

To study a possible etiologic role of sex hormones on the development of simple goiter, estradiol benzoate (EB), testosterone propionate (TP), or methyltestosterone (MT) were administered subcutaneously daily for 14 days to normal rats or rats receiving small doses of methylthiouracil (MTU). In agreement with our previous report, it was found that goiter with normal radioiodine uptake followed the intraperitoneal administration of small doses of MTU. It was also shown that goiter with high radioiodine uptake was produced by large doses of EB (50 or 100 μg.) but not by small doses (1 μg.). Small or large doses of EB have failed to augment the goiter produced by small doses of MTU. Furthermore, unlike the findings in man, large doses of EB failed to increase thyroxine-binding capacity of the plasma proteins in the rat. TP, over a wide range of dose, produced a marked growth of the seminal vesicles, but failed to reduce the size of the normal thyroid or the thyroid stimulated by small doses of MTU. TP also failed to reduce the thyroxine-binding capacity of plasma proteins. Although the data on the rat do not support the hypothesis that sex hormones affect the development of goiter by altering the thyroxine-binding capacity of plasma proteins, the data are not necessarily applicable to the physiology of the human thyroid because of differences in thyroxine-binding proteins between man and rat.

ADRENOCORTICAL INFLUENCES ON GROWTH OF REPRODUCTIVE STRUCTURES OF THYMECTOMIZED AND SHAM-THYMECTOMIZED RATS.

It was previously demonstrated that sham thymectomy, but not thymectomy, retarded the growth of ventral prostate glands and seminal vesicles of Long-Evans rats subjected to surgery at 44–46 days of age and autopsied 3 weeks later. Unilateral adrenalectomy abolished the observed differences between thymectomized and sham-thymectomized rats by preventing the retardation. Administration of cortisone acetate (Cortogen) led to reduction in weight of secondary reproductive structures of unoperated, shamthymectomized and thymectomized rats. Prostate glands and seminal vesicles of cortisone- treated thymectomized rats were significantly heavier than those of cortisone-treated sham-thymectomized rats. It is suggested that the thymus gland may influence both the adrenocortical response to stress and the secondary changes which follow enhanced secretion of corticosteroids. (Endocrinology 75: 167, 1964)

Vitamin A and reproduction in rats

Retinoic acid (vitamin A acid), the carboxylic acid corresponding to the primary alcohol retinol (vitamin A), has previously been thought to fulfil all the functions of vitamin A except in vision, since rats fed a diet deficient in retinol but supplemented with retinoic acid grow well, outwardly appearing healthy, yet become blind. This paper reports that female rats on such a diet had normal oestrous cycles and became pregnant when mated, but always resorbed the foetuses and no litters were born. The first abnormalities detected were necrosis and slight polymorph infiltration around the periphery of the placental disk about the sixteenth day of pregnancy. Supplementation with retinol as late as the tenth day resulted in the birth of a healthy litter. Retinoic acid therefore maintained the early but not the later stages of gestation. When very small amounts of retinol were given during pregnancy, dead or weak young were born; on higher supplements of the vitamin, litters were weaned successfully. By this means young rats were produced with negligible stores of retinol. Male rats fed retinoic acid but not retinol had small and often oedematous testes. The germinal epithelium sloughed off and in some tubules the lumen was obliterated, but in others the lumen remained, and in these some spermatocytes and spermatogonia were held tenaciously. The seminal vesicles were smaller than in controls given retinol. In rats born with negligible stores of retinol—see above—and maintained on retinoic acid, the testes remained infantile; spermatids were never formed. Feeding retinol restored spermatogenesis in degenerate testes and promoted the normal development of testes that had remained infantile; it also ensured the growth of the seminal vesicles. Retinoic acid did not therefore serve in reproduction, although it replaced the true vitamin in maintaining life, growth and general health. Besides the latter so-called systemic function, vitamin A must have a discrete and specific role in reproduction, viz. that performed by retinol but not by retinoic acid. From among the many previously reported features of disordered reproduction in vitamin A-deficient animals, it was possible to distinguish which had arisen from a failure of this specifically ‘reproductive’ role and which from a ‘systemic’ deficiency. The inactivity of retinoic acid in reproduction demonstrates that in rats vitamin A has not two, as previously thought, but three dissociable modes of action: (1) systemic; (2) in vision; and (3) in reproduction.

On the metabolic action of testosterone and related compounds. V. The effect of testosterone on the nucleic acid composition of seminal vesicles and kidneys of mice.

ABSTRACT 1. Changes in nucleic acid composition of the seminal vesicles and kidneys of mice which occur after castration and after substitution therapy with testosterone in castrated animals were studied. 2. It was found that after castration both the DNA and RNA content of the seminal vesicles decreases. The concentration of DNA, however, increases while the RNA concentration in this tissue decreases. 3. These changes are reversed by treatment with testosterone. The rise in RNA content precedes the increase in DNA content of this organ. 4. No changes in DNA content of the kidneys were found either after castration or after treatment with testosterone of castrated mice. The RNA content of this organ changed parallel with the changes in weight. 5. These results strongly suggest that with testosterone treatment, the growth of the seminal vesicles is due to hyperplasia as well as hypertrophy, while the increase in kidney weight is due only to hypertrophy.

Effects of gonadotrophins and androgens on the sex organs of the estrogen-treated male rat.

SummaryThe effects of various pituitary extracts and androgenic steroids on the sex-organs of the estrogen-treated immature male rat were studied. Testosterone induced growth of the seminal vesicles and ventral prostate with similar threshold-doses and dose-response slopes for both organs, but did not cause testicular enlargement except at high dose levels. Purified ovine LH and pregnenolone induced growth of the ventral prostate but the dose-response slope was considerably less than that obtained with testosterone, androstenedione, 17 α hydroxyprogester-one, progesterone, dehydroepiandrosterone or crude pituitary extracts. Unlike testosterone, neither purified LH nor pregnenolone induced growth of the seminal vesicles except at very high dose levels, but both caused enlargement of the testes at doses that barely effected prostate size.

Morphology of bull testes and seminal vesicles in relation to testicular androgens

Correlations were studied between various morphological and functional characteristics of the testis and seminal vesicle in bull calves and bulls, ranging in age from 28 days to 17½ years. Data obtained by the analysis of testosterone and androstenedione in the testes, and of fructose and citric acid in the seminal vesicles, were related to results of gross anatomical and histological measurements of these organs. The mean diameter of the seminiferous tubules was adopted as a means of assessing testicular function, since it was shown that this diameter is related to the weight of the testis as a whole (r= 0.92,P&lt; 0.001), to the arrangement of the interstitial tissue, and to definite stages in the differentiation of the seminiferous epithelium . At 28 days, when the bull testis is relatively inactive, both as regards spermiogenesis and the endocrine function, the mean diameter of the seminiferous tubules was 48 μ. At the age of 90 days, coinciding with the appearance of spermatogonia in the testes, and just prior to the marked increase in fructose and citric acid formation in the seminal vesicles, it was 66 μ. At about 4½ months, when the androstenedione/testosterone ratio falls abruptly, the tubular diameter increased to more than 90 μ. By 7½ months, when the first spermatozoa appear in the tubules, it had risen to 177 μ. A significant correlation was established between the growth and secretory activity of the seminal vesicles and the diameter of the seminiferous tubules in bull testes. Correlation coefficients were established between the tubular diameter and the following: the weight of the seminal vesicles,r= 0.95,P&lt; 0.001; the contents o f fructose and citric acid in the seminal vesicles,r= 0.81,P= 0.01 to 0.001; and the concentrations of fructose and citric acid in the seminal vesicles,r= 0.82 andr= 0.76, respectively,P= 0.01 to 0.001.

A complementary action of corticosterone and dehydroepiandrosterone on the mouse adrenal, with observations on the reactivity of reproductive tract structures to dehydroepiandrosterone and 11-hydroxy-androstenedione.

Dehydroepiandrosteronc (DHA) and corticosterone (B) had complementary and roughly additive effects in reducing adrenal weights in mice when the adrenal X zone was present. DHA suppressed the X zone whereas B reduced the size of the zona fasciculata. DHA had no effect on adrenal weights in mature mice in which the X zone was not present. The suppression of the X zone by DHA was compatible with apparently normal ovarian and uterine maturation. X zone suppression was produced by doses of DHA which gave only minimal stimulation to seminal vesicle growth, but had pronounced effects on the growth of the preputial glands and the phallus in either sex. 11-hydroxy-Δ4-androstcnedione was somewhat less active than DHA in suppressing the X zone, but its effects on reproductive tract structures were of the same order of magnitude If the reactivity of the human embryonic phallus is similar to that of the immature rodent, excessive production of either of these two adrenal androgens could be expected to account for the ...

A myotrophic agent and gonadotrophin inhibitor, 19-nortestosterone-17-benzoate.

19-Nortestosterone-17-benzoate, a new ester of 19-nortestostcrone, has been ompared with testosterone propionate for several biological activities. Testosterone propionate and 19-nortestosterone-17-bcnzoate are myotrophic and suppress production or release of pituitary gonadotrophins. Unlike testosterone propionate, the 19-nortestosterone derivative elicits these responses in doses which do not stimulate growth of seminal vesicles and ventral prostate in rats. The uterotrophic, anti-estrogenic and progestational potenciesof the 2 androgens are similar. 19-Nortestosterone-17-benzoate is devoid of estrogenic ativity. A 6- week study in intact and castrate male and female rats demonstrate that the biologic properties of 19-nortestosterone-17-benzoate are typical of those of an androgen. This steroid was orally inactive at the dose tested.

Seminal vesicle growth as a function of androgen stimulation in mice.

One hundred fourteen mice castrated at weaning were given different dosages of testosterone propionate by daily subcutaneous injection for 20 days. The seminal vesicle weight was chosen as the quantitative indicator of growth response in secondary sex organ. Thirty-four noncastrates were used for comparison. The growth of the seminal vesicles in response to the different dosages of hormone stimulation was shown, as are population growths, to be well fitted with the logistic curve. It was found also that the point of inflection of the dose-response curve was at a seminal vesicle weight which was close to the seminal vesicle weight of the untreated controls.

Testosterone beta-cyclopentylpropionate: a new long-acting androgen.

THE general acceptance of testosterone propionate by the parenteral route for therapy of androgen deficiencies is based primarily on early studies with several esters of testosterone. After the early initiation of this work by Ruzicka (1, 2), the intensity and prolongation of androgenic response to many esters was investigated (3,4, 5). None of these was found to be of significantly greater activity than the propionate, which became generally accepted as the most effective form of testosterone. Miescher, Wettstein and Tsc hopp (6) reported that aliphatic short-chain fatty acid esters of testosterone effected greater seminal vesicle growth response in young castrate rats than did either free testosterone, or aliphatic long-chain fatty acid esters. The palmitate and stearate produced only minimal, if any, androgenic response. Recently Mooradian, et al. (7) have reported that certain alkoxy and alkylmercapto acyl esters of testosterone have somewhat higher activity than testosterone propionate when immediate...

Effect upon the compensatory renal hypertrophy by cortisone and other adrenal cortex steroids

In contrast to the inhibitory effect exercised by Cortisone upon connective and lymphatic tissue, of the rat it produces an increase in the compensatory hypertrophy of the remaining kidney after removal of the other one when given in doses of 1 and 5 (2.5) mg every second day. 11-Desoxycorticosterone or 11-descoxy-17-hydroxy-corticosterone (Compound S) have no influence on the development of compensatory renal hypertrophy. Cortisone does not diminish the hyperplasia of the thyroid gland after treatment with methyl-thiouracil or the growth of the seminal vesicles which occurs after treatment with testosterone.

Interference with Testosterone-induced Growth of the Seminal Vesicles and Coagulating Glands in Male Mice by a Folic Acid Antagonist

IT has been established that adequate amount, of folic acid are necessary for the elicitation by œstrogens of the growth response of the female genital tract in the chick1,2 and monkey3. Recently, it has been reported that folic acid antagonists markedly decreased the growth response to œ"strogens of the genital tracts of the female chick4,5, rodent6 and frog7.

THE ACTION OF EXTRACTS OF ANTERIOR PITUITARY AND OF PREGNANCY URINE ON THE TESTES OF IMMATURE RATS AND MONKEYS*

Several score of papers dealing with the action of extracts of pregnancy urine and of the anterior pituitary on the male genital system bear witness to the attention which has been focused on this point since 1927. In our earlier work on the effect of implants (Smith and Engle), we noted that the distinct growth of the seminal vesicles of implanted animals demonstrated an activity of the interstitial cells, though morphological changes, were not directly observable on these cell bodies. These observations have been greatly extended by many investigators,1 who note varying degrees of hypertrophy and hyperplasia in the interstitial cells after treatment with extracts of anterior pituitary or pregnancy urine. With the exception of the report of Balawenetz (1930), no one has reported success in hastening the formation of spermatids or spermatozoa, in an immature male mammal, and it is generally agreed that, in the male at least, none of these gonad-stimulating factors are directly concerned with gametogenesis. These accumulated observations on the prepubertal male emphasize the position taken a year ago in regard to the action of anterior pituitary principles on the female (Engle, 2). We are dealing with a genital acceleration mainly of the hormone producing structures but have not produced true precocious puberty. That phenomenon is more complex than may be explained by the action of a single hormonal factor.