Showing papers on "Testosterone published in 1970"

Dihydrotestosterone in prostatic hypertrophy: I. The formation and content of dihydrotestosterone in the hypertrophic prostate of man

Abstract: To explore the relation between androgens and prostatic hypertrophy in man, the concentrations of testosterone, dihydrotestosterone, and androstenedione and the rate of conversion of testosterone to dihydrotestosterone have been measured in normal and hypertrophic prostate tissue First, a double isotope derivative technique was adapted for the measurement of tissue androgen content in 15 normal and 10 hypertrophic prostates Although there was no significant difference in the content of androstenedione and testosterone between the two types of tissue, the content of dihydrotestosterone was significantly greater in the hypertrophic tissue (060 +/-010 mug/100 g) than in the normal glands (013 +/-005 mug/100 g) Second, a regional study was performed in three normal prostates and four glands with early hypertrophy, and it was demonstrated that the dihydrotestosterone content was two and three fold greater in the periurethral area where prostatic hypertrophy usually commences than in the outer regions of the gland Finally, the rate of conversion of testosterone to dihydrotestosterone has been measured under standardized conditions in tissue slices from 4 normal and 20 hypertrophic prostates There was no significant difference in the rate of dihydrotestosterone formation between the two types of gland (60 +/-08 and 78 +/-05 mumumoles/15 mg of tissue per hr) While the mechanism by which dihydrotestosterone accumulation occurs remains unexplained, it is possible that the local accumulation of dihydrotestosterone may be involved in the pathogenesis of prostatic hypertrophy in man

Inhibition of catecholamine Uptake2 by steroids in the isolated rat heart

Abstract: Various steroids (17-β-oestradiol, corticosterone, deoxycorticosterone, progesterone, testosterone and androsterone) produced a dose-dependent inhibition of the uptake of 3H-noradrenaline by the Uptake2 mechanism in the isolated perfused heart. It is suggested that these results may explain the potentiating effects of such steroids on the responses of vascular smooth muscle to catecholamines.

Concentrations of putrescine and polyamines and their enzymic synthesis during androgen-induced prostatic growth.

Abstract: 1 Castration of adult rats resulted in marked decreases in the amounts of putrescine, spermidine and spermine in the ventral prostate gland Spermidine concentrations decline rapidly over the first 11 days after androgen withdrawal, reaching a value of only 12% of normal controls Spermine concentrations diminish more slowly, reaching 24% of normal within 11 days The spermidine/spermine molar ratio falls from 09 to 046 under these conditions Putrescine concentrations decrease by 70% at 7 days after castration and then remain constant for some days 2 After daily injections of testosterone propionate to rats castrated 7 days previously, prostatic spermidine and putrescine concentrations increase significantly within 24h; normal or even greater values are observed within 8 and 4 days respectively In contrast, the spermine concentration does not increase until 5 days after commencement of androgen treatment 3 The activities of two enzymes involved in polyamine biosynthesis (ornithine decarboxylase and a putrescine-activated S-adenosyl-l-methionine decarboxylase system) were greatly decreased soon after castration: after 7 days the respective values were 15% of normal for ornithine decarboxylase and 7% of normal for putrescine-dependent decarboxylation of S-adenosyl-l-methionine Injection of testosterone propionate into animals castrated 7 days previously induced a rapid increase in both enzymic activities: ornithine decarboxylase was doubled in 6h, and increased three- to four-fold within 48h, whereas the putrescine-dependent decarboxylation of S-adenosyl-l-methionine doubled in 3h and increased tenfold within 48h of commencement of daily androgen treatments 4 The activity of these enzyme systems was very low in the ventral prostates of hypophysectomized rats and was increased by administration of testosterone in a manner similar to that found in castrated rats 5 Alterations in the activity of two ventral-prostate enzymes involved in ornithine production (arginase) and utilization (ornithine-2-oxoglutarate transaminase) that result from changes in the androgenic status of rats are described 6 The findings presented suggest that the activities of ornithine decarboxylase and the putrescine-dependent S-adenosyl-l-methionine decarboxylase system, rather than ornithine concentrations, are rate-limiting for the formation of putrescine and polyamines in rat ventral prostate 7 The relation of polyamines to androgen-induced prostatic growth is discussed with particular reference to the biosynthesis of proteins and nucleic acids

The intranuclear metabolism of testosterone in the accessory organs of reproduction.

Abstract: Publisher Summary This chapter discusses the intranuclear metabolism of testosterone in the accessory organs of reproduction. Testosterone is taken up by nuclei of the accessory organs of male reproduction. Within these nuclei, testosterone may undergo at least two fates; it may either be bound to a protein of the chromatin or it may be reduced to dihydrotestosterone prior to or as a step in the binding process. The implications of these events in regard to the mechanism of action of the hormone are unclear. On the one hand, it is possible that specific testosterone metabolites may have different effects within a single target tissue. It seems more likely, however, that the various metabolites have different binding affinities for the same binding site(s) and that any differences in the effects of different metabolites can, as a consequence, be explained in qualitative terms. The physiological meaning of dihydrotestosterone formation is also uncertain. On the basis of the remarkable growth-promoting effects of dihydrotestosterone on prostate both in vivo and in organ culture, the correlation between the rate of dihydrotestosterone formation in skin of man and the known growth response of the skin to testosterone, and the striking relation between prostatic growth in different species and the rate of this conversion, it is tempting to speculate that dihydrotestosterone formation may have some special relation to the growth-promoting effects of testosterone.

Structure and Function of Rat Testis Through Pubescence

Abstract: The histology, histochemistry, testosterone content and secretion of the rat testis were studied from 20 to 90 days of age. Histologic maturation of Leydig cells preceded the phase of rapidly increasing testosterone secretion. The disappearance of Leydig cell perinuclear basophilia was correlated with increasing Leydig cell function. The testosterone content per Leydig cell increased linearly from 20 to 90 days although total testis content of testosterone decreased due to decreasing Leydig cell number. (Endocrinology 86: 1298, 1970)

Male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency.

Abstract: This is the first report of a male with 17alpha-hydroxylase deficiency resulting in male pseudohermaphroditism, ambiguous external genitalia, absence of male secondary sexual characteristics, and gynecomastia at puberty. Diagnosis was based on extensive studies of steroid metabolism including the following: low urinary excretion of 17-ketosteroids and 17-hydroxycorticoids which did not increase after ACTH; no response of very low plasma testosterone and dehydroepiandrosterone to adrenocorticotropin (ACTH) or chorionic gonadotropin; and low urinary aldosterone and plasma renin which increased after dexamethasone. Secretion rates of 17-hydroxylated steroids, cortisol (F) and 11-desoxycortisol (S), were very low while desoxycorticosterone (DOC) and corticosterone (B) secretion rates were increased sevenfold. Results expressed as milligrams per meter squared per day were as follows: F, 1.3; S, 0.023; DOC, 0.35; and B, 16 (mean normal values were F, 7.5; S, 0.26; DOC, 0.055, and B, 2.2). Plasma gonadotropins were markedly increased (FSH, 106; LH, 364 mIU/ml). Testicular biopsies revealed interstitial-cell hyperplasia and early spermatogenesis. Karyotype was 46/XY. Pedigree showed no other affected member. At laparotomy ovaries, uterus, and fallopian tubes were absent, vas deferens was incomplete, and prostate was present. External genitalia consisted of small phallus, bifid scrotum, third-degree hypospadias, and small vagina. At puberty there was no growth of body hair or phallic enlargement. Biopsy of marked gynecomastia showed both ducts and acini. Testosterone administration produced virilization. Sexual ambiguity demonstrates strong dependence of external genitalia on androgens for male differentiation. Suppression of Mullerian structures occurred despite female levels of testosterone indicating this step in male differentiation is not testosterone dependent. Pubertal breast development in this male supports the concept of femaleness during ontogeny unless counteracted by male factors. Diagnosis of other adrenocortical enzymatic deficiencies is excluded by the steroidal studies. The clinical response to testosterone excludes testicular feminization. Deficiency of 17-hydroxylation must be added to the cause of male pseudohermaphroditism.

Dihydrotestosterone in prostatic hypertrophy: II. The formation and content of dihydrotestosterone in the hypertrophic canine prostate and the effect of dihydrotestosterone on prostate growth in the dog

Abstract: Three types of studies have been performed in immature, mature, and hypertrophic prostate glands of the dog. First, the concentrations of testosterone and dihydrotestosterone have been measured in the three types of gland. Dihydrotestosterone was the predominant hormone recovered in all prostates studied and was present in approximately five times higher concentration in the hypertrophic as compared to the other types of dog prostate. Second, pharmacological doses of dihydrotestosterone were administered to castrated dogs for 9 months and resulted in a distinct acceleration of prostatic growth as compared to testosterone treatment. Third, the rates of formation and degradation of dihydrotestosterone were measured in normal and hypertrophic tissue and were found to be essentially the same. These observations suggest that dihydrotestosterone accumulation may be causally linked to the development of canine prostatic hypertrophy. However, the mechanism by which dihydrotestosterone accumulates in the prostate remains to be determined.

Brain serotonin and sexual differentiation of the nervous system.

Abstract: Serotonin concentration was determined in the brains of male and female rats on the 1st, 4th, 8th, and 12th day after birth. It was observed that while the amount of 5HT is comparable within the two sexes up to day 8, it rises significantly in females on day 12. This elevation in serotonin levels could be prevented if the females were injected with testosterone propionate on the day of birth. By comparison, males castrated at birth had brain serotonin levels comparable to those in intact females and significantely greater than those in intact littermates. These results suggest that the serotonin concentration may be related to the process of sexual differentiation of the brain, since this concentration is modified by the same procedures that induce androgenization. It is also suggested that the testosterone liberated by the neonatal gonad may modify the metabolism of brain serotonin only on day 12, which period corresponds to the time of the sexual differentiation of the structures that control gonadotrophin secretion.

Effect of Testosterone on Growth Hormone Secretion in Patients with Anorchia and Delayed Puberty

Abstract: The effect of testosterone on plasma growth hormone response to hypoglycemia was studied in 4 patients with anorchia, in a patient with delayed puberty, and in a patient with panhypopituitarism. Insulin tolerance tests were performed a) without testosterone therapy, b) 2 days after a single injection of testosterone, and c) in 3 patients after 2–3 months of full replacement therapy. Testosterone led to an increased release of growth hormone in all 4 patients with anorchia and in the boy with delayed puberty. This increase appeared 2 days after a single injection of testosterone; it became still higher after 2–3 months of full replacement therapy. In the patient with panhypopituitarism, no growth hormone response was observed. The normalization of growth hormone release after one injection of testosterone might be helpful to exclude isolated growth hormone deficiency in boys with delayed puberty and small stature who present a doubtful growth hormone response to hypoglycemia.

Anabolic and Androgenic Effect of Testosterone in Sexually Immature Boys and Its Dependency on Growth Hormone

Abstract: The effect of a long-acting testosterone preparation1 on growth, on skeletal maturation and on secondary sex characteristics was studied in 24 boys with sexual immaturity of different causes. In patients without growth hormone deficiency dosages above 100 mg/m2/month lead to a maximum growth velocity during the first 6 months of treatment (catch-up growth). Smaller initial dosages followed by a gradual increase to 100–150 mg/m2/month, lead to an imitation of the normal pubertal growth spurt. The time from the start of treatment to the development of axillary hair is inversely proportional to the mean dosage. In patients with growth hormone (GH) deficiency the response is less marked with respect to growth and to the development of secondary sex characteristics. To exert its full growth-promoting anabolic effect, testosterone apparently needs the presence of GH. To exert its full androgenic effect on the secondary sex characteristics, pituitary hormones are also necessary, but it is not clear whet...

Stimulation of Mammalian Erythropoiesis by 5β-H Steroid Metabolites

Abstract: The effects of a number of steroid compounds on erythropoiesis in normal and polycythemic mice were examined. Of the steroids that stimulated erythropoiesis, the hormone testosterone and certain 5β-H C19 and C21 nonhormonal metabolites were the most effective. Anti-erythropoietin abolished the erythropoiesis-stimulating effects of testosterone but not those exerted by the 5β-H steroid, 11-ketopregnanolone. Similarly, testosterone but not 11-ketopregnanolone evoked the production of erythropoiesis-stimulating factor in rats. It is concluded that two mechanisms underlie the stimulating actions of steroids on erythropoiesis; one through the production of erythropoietin and the second involving a more direct influence on the blood-forming tissues. The 5β-H steroid metabolites are postulated to act on erythropoiesis via the latter mechanism.

Adrenocortical function in the hamster. Sex differences and effects of gonadal hormones.

Abstract: Adrenal weight is greater in the male hamster than in the female, a sex difference opposite that in other rodent species. Prepuberal gonadectomy results in decreased adrenal weight in both sexes; testosterone or estradiol replacement restores the weight to the control level. Sex differences in adrenocortical function accompany those in weight, with the male having higher plasma corticosteroids, greater steroid output in vitro by adrenal slices or homogenates, and greater steroid secretion in vivo than the female.Hepatic metabolism of cortisol in vitro is greater and biological half-life (t½) of cortisol is shorter in the male. Prepuberal orchiectomy results in decreased plasma corticosteroids at rest and after ether stress, decreased steroid output in vitro by adrenal slices and homogenates, and decreased steroid secretion in vivo compared with the intact male. Hepatic metabolism of cortisol in vitro is decreased and the t½ of cortisol is prolonged after orchiectomy. Testosterone replacement reverses or p...

Androgen secretion by the fetal and neonatal rhesus monkey.

Abstract: The capacity of the gonad to produce androgens was studied in the fetal rhesus monkey. At approximately days 45 and 60 of fetal life the testes converted 14C-pregnenolone to testosterone (T) and androstenedione (Δ) in vitro. By days 45, 60 and 80 of fetal life, the ovary is relatively quiescent with regard to its ability to synthesize T and Δ from pregnenolone. Measurement of T and Δ in pools of umbilical artery plasma (UAP) and gonads of the monkey at 100, 125 and 150 days of gestation showed more T in plasma from male compared to female fetuses. Δ Concentrations did not differ with fetal sex. Similarly, greater quantities of T were found in the systemic plasma of mothers with male fetuses. During the neonatal period, androgens in the plasma were high on days 1 or 2 but diminished to low levels with time. Fetal testicular tissue contained large quantities of T that fell to low or undetectable amounts in the neonatal period. Ovarian or adrenal tissue contained Δ but no T. These data demonstrate that the f...

Sites of hormone production in the mammalian testis, and their significance in the control of male fertility.

Abstract: The purpose of this paper is to summarize the evidence that there are 2 main lines of hormone production in the testis to discuss the relationship between the 2 systems and to show how the available information could be of practical value in achieving a suitable method of fertility control. In a wide variety of mammals including man a mass of cytoplasm or "residual body" is shed by each germ cell just before it passes down the seminiferous tubule. This material is phagocytosed by the Sertoli cells by an increase in lipid content. This lipid wanes as spermatogenesis proceeds to a low level after meiosis has been completed and the cycle is repeated as each generation of spermatids attains maturity. The administration of FSH causes a reduction in the lipid/sterol content of the Sertoli cells of estrogen-treated rats. It is ineffective when the germinal epithelium has been destroyed. The absence of some releasing factor from the germ cells is assumed. Morphological evidence endorses the view that the stereogenetic activity of the tubules is due to the Sertoli cells. In view of the evidence it is the androgens elaborated by the Sertoli cells that are responsible for the normal maintenance of spermatogenesis. This effect is related to the androgenicity of the compounds of which testosterone is probably the most important. Maintenance of the secondary sex characteristics under normal conditions is by the Leydig cells. When FSH is administered to estrogen-treated rats the large amount of lipid/cholesterol present in the Sertoli cells is metabolized and spermatogenesis is restored. Androgen production by the Sertoli cells seems to be governed by the availability of FSH. A way to control spermatogenesis without affecting secondary sex characteristics may be to use an agent that inhibits the production or activity of either FSH or the tubular androgens. Creating an autoimmune reaction would not be readily reversible. Also the secondary sex characteristics would be affected. Use of an oral androgen at a dose level sufficient to depress the level of FSH and maintain the secondary sex characteristics but too low to stimulate the germinal epithelium would achieve fertility control in man. Most oral androgens available appear to be C-17-alklated derivatives of testosterone and androstenediol which are liable to produce impairment of hepatic function. Mesterolone lacks this C-17-alkyl group. In animal experiements the size of the testicles is reduced by estrogen-androgen administration (depending on dosage employed) but there is an increase in libido. Thus there may be developed the male equivalent of the female "pill" as an oral contraceptive.

Pituitary-Leydig Cell Function in Uremic Males

Abstract: Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and testosterone binding affinity (TBA) were measured in 15 uremic males. The mean control serum testosterone level was 262 ng/100 ml. The testosterone value doubled during acute stimulation with human chorionic gonadotropin (HCG) 4000 U daily, a normal percentage increase. Although LH was significantly elevated, the elevation was inadequate to promote normal Leydig cell function in most instances. This impaired pituitary-Leydig cell mechanism was found in association with a normal TBA. Acute increases in serum testosterone produced by HCG did not alter TBA from control values.

Hormone Secretion by the Human Ovaries

Abstract: The secretory function of both human ovaries was studied simultaneously by comparing the concentrations of several steroids in the effluent blood from the two ovaries with their concentrations in the

Estradiol "receptors" in hypothalamus and anterior pituitary gland: inhibition of estradiol binding by SH-group blocking agents and clomiphene citrate.

Abstract: Estrogen-sensitive tissues selectively take up and retain estradiol and other biologically active estrogens by binding them to “receptors” present in cytoplasm and nuclear fractions. Such “receptors,” already isolated from myometrium and endometrium of several species, should be present in pituitary gland and hypothalamus if binding of the hormone is analogous and also necessary for its specific biological activity in these tissues. To test this hypothesis, we incubated various bovine hypothalamic tissues and pituitary glands with 3Hestradiol (10−10 to 10−9m) and isolated the radioactive steroid “receptor” complex by density gradient ultracentrifugation. The amount of “receptor”-bound radioactivity present in fractions 1-10 of the gradient was greatest with cytoplasm of pituitary gland and decreasing amounts were observed in median eminence, paraventricular portions of the anterior and posterior hypothalamus and little if any specific binding occurred with that of the parietal cortex. Binding of neither r...

Essential Role of Testosterone in the Sexual Stimulation induced by p -Chlorophenylalanine in Male Animals

Abstract: P-CHLOROPHENYLALANINE (POP A), a compound that inhibits the synthesis of 5-hydroxytryptamine (5-HT) without affecting that of noradrenaline1, produces compulsive sexual activity in male animals. This effect was observed by Ferguson et al. in cats2, by Tagliamorite et al. in rats and rabbits3 and by Shillito in rats4. The compulsive sexual activity is not caused by a depletion of indole hormones in the pineal gland, for we found that PCPA elicited sexual stimulation in pinealectomized animals. Further, sexual stimulation induced by PCPA is inhibited by restoring brain 5-HT levels with 5-hydroxy-tryptophan3, a precursor of 5-HT. This effect thus seems to be associated with the depletion of brain 5-HT. Moreover, because sexual stimulation induced by PCPA is potentiated when catecholamine levels in brain are increased with pargyline, an inhibitor of monoamine oxidase, we postulated that both brain 5-HT and catecholamines control sexual behaviour in male animals, 5-HT inhibiting sexual behaviour and catecholamines stimulating it. Our results show that the effect of PCPA on sexual behaviour in male rats is not only prevented by castration but is strikingly potentiated by testosterone.

Androgenic and male-inducing effects of 11-ketotestosterone on a teleost, the medaka (Oryzias latipes)

Abstract: The androgenic and the male-inducing (androtermonic) activities of 11-ketotestosterone were evaluated respectively by its abilities to stimulate a secondary sex character and to reverse gonadal sex differentiation in a teleost, the medaka (Oryzias latipes). The median effective dose (ED 50) of this steriod necessary to induce the formation of papillar process on the anal fin was 37 μg/g of food. The androgen is therefore about 8 times potent than testosterone propionate and 17 times more potent than pure testosterone in the same test. The ED 50 for androtermonic activity (reversal of genetic females to phenotypic males) was found to be about 110 μg/g of food. Compared with testosterone propionate the 11-keto compound is about five times more potent. Thus, in teleosts, 11-ketotestosterone appears to be the most potent androgen of vertebrate origin for both androgenic and androtermonic potencies. The ratio of androtermonic to androgenic potencies (ED 50s) for 11-ketotestosterone is 3.0.

In Vitro Synthesis of Cholesterol and Testosterone from Acetate by Rat Epididymis and Vas Deferens

Abstract: SummaryThe epididymis and vas deferens from the rat are capable of synthesizing cholesterol and testosterone from acetate. The significance of androgen synthesis by the epididymis is discussed.