Showing papers on "Testosterone published in 1974"

Testosterone Formation and Metabolism During Male Sexual Differentiation in the Human Embryo

Abstract: The formation by the gonads of [3H] testosterone from [7α-3H]pregnenolone and [1,2-3H] progesterone and the metabolism of [1,2-3H]testosterone by various tissues have been studied in 33 human fetuses that varied in age from phenotypically undifferentiated stages (1–3 cm crown-rump length) to sexually differentiated male and female embryos greater than 21 cm in length. In the first series of studies utilizing thinlayer and celite column chromatography for quantification of the metabolic products following incubation of the gonads with the C21 steroids, it was concluded that testosterone is the principal androgen formed by the fetal testis at the time of male sexual differentiation. The capacity for testosterone formation from these precursors was shown to rise from undetectable levels at 1–3 cm of development to maximal rates of about 150 pinoles/10 mg tissue/2 hr in the testes obtained from embryos of 7.1–9 cm crown-rump length, a sequence that correlates closely with the androgenmediated events ...

Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle.

Abstract: In order to assess the ovarian and adrenal contribution to peripheral levels of testosterone (T), 5α-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) in premenopausal women, six normally menstruating subjects were studied during two complete mentrual cycles. The first cycle served as control and dexamethasone was given during the second cycle. Plasma cortisol (F) was measured to assess the degree of adrenal suppression. Plasma progesterone (P), 17-hydroxyprogesterone (17-P) and estradiol-17β (E2) served as indirect indices of ovulation. The estimation of plasma LH located the midcycle peak and the data for all steroids were evaluated in relation to the LH peak. All cycles studied were apparently ovulatory, as judged by the plasma levels of P, 17-P and E2. Dexamethasone treatment had no detectable effect on the levels of these three steroids. Assuming that dexamethasone suppressed completely the adrenal cortex and had no detectable effect on ov...

The Male Reproductive System

Abstract: The male reproductive system consists of external reproductive organs, penis and scrotum, and internal reproductive organs: testes, a duct system, and accessory glands. The adult, paired testes produce both male sex hormones (androgens) and sperm cells (spermatogenesis). Androgens, primarily testosterone, are necessary for development and maintenance of male behavioral and physical manifestations and for spermatogenesis.

Further studies on Leydig cell function in old age.

Abstract: Pathophysiological mechanisms leading to a decreased Leydig cell function in old males were studied. Increased basal plasma LH and FSH levels, an increased pituitary reaction to LHRH 200 μg iv, and a decreased responsiveness of the Leydig cells to hCG stimulation, lead to the conclusion that the decreased Leydig cell function in old age has a primary testicular origin. The plasma estrone and estradiol levels are slightly but significantly increased in elderly males, the free estradiol concentration is however unchanged. There exists a highly significant correlation between the (log transformed) apparent free testosterone concentration and LH and FSH levels suggesting that the feedback of the gonadotropin secretion is regulated via the free rather than via total testosterone levels.

Androgen transport and receptor mechanisms in testis and epididymis

Abstract: Spermatogenesis is an androgen dependent process which can be maintained in hypophysectomized rats by the administration of either testosterone (1) or 5α-dihydrostestosterone (2). Gonadotrophins may exert their effects on spermatogenesis indirectly by way of androgens. The sole action of LH appears to result from the stimulation of testosterone synthesis by the interstitial cells of Leydig. FSH is necessary for the full maintenance of spermatogenesis, but its effects can be mimicked by androgen and blocked by the anti-androgen, cyproterone, indicating that its action is linked in series with androgen (1) or that androgen is the mediator of FSH action.

Gonadotrophin-releasing Hormone Therapy in Hypogonadal Males with Hypothalamic or Pituitary Dysfunction

Abstract: Subcutaneous self-administration of synthetic gonadotrophin-releasing hormone 500 μg eight-hourly for up to one year by 12 male patients (five prepubertal) with clinical hypogonadism due to hypothalamic or pituitary disease resulted in the synthesis and continued release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). There was a rise in circulating androgen levels in all patients. Improvements in pubertal ratings were seen in some prepubertal patients. Potency returned in the adults and spermatogenesis was induced and maintained in the four patients who had received treatment for more than four months, total counts reaching between 7·8 and 432 × 106 spermatozoa. A fall in the FSH response to the releasing hormone occurred during spermatogenesis though LH was little affected. During the initial weeks of therapy FSH secretion usually occurred before that of LH though LH secretion was greater as treatment continued. FSH secretion also persisted for longer when treatment was stopped.

Induction of a lactogenic receptor in rat liver: influence of estrogen and the pituitary.

Abstract: A receptor exists in female rat liver with high specificity for lactogenic hormones. Previous work showed the receptor level increased at the time of puberty in female but not male animals. Pregnancy caused a further substantial increase. Here we show that estrone (50 μg/day) administration to male rats induced a 10- to 30-fold increase in specific binding of ovine prolactin and human growth hormone after 8-12 days with a significant increase first seen after 4 but not 2 days of injection. In females, this regimen increased binding to pregnancy levels. In prepuberal (20-days-old) male and female rats, estrone was also markedly stimulatory. The binding sites for ovine prolactin and human growth hormone were of high affinity in liver membranes from both female and estrone-treated male rats (Ka = 0.6 to 1.4 × 109 M-1). Estrone and estradiol were equally effective in inducing the lactogenic receptor. Estriol (50 μg/day), progesterone (500 μg/day), human placental lactogen (1 mg/day), and testosterone (100 μg/day) were without influence. Hypophysectomy drastically decreased the levels of lactogenic receptor in mature female rats, and estrogen treatment failed to restore receptor levels to normal. Hypophysectomized male rats were also unresponsive to estrogen. Throughout these studies the specific binding of 125I-labeled insulin remained relatively constant. This work demonstrates estrogen induction of a lactogenic receptor. The pituitary gland appears to have a critical, though presently undefined, role in the induction process.

Secretion of Unconjugated Androgens and Estrogens by the Normal and Abnormal Human Testis before and after Human Chorionic Gonadotropin

Abstract: The secretion of androgens and estrogens by normal and abnormal testes was compared by determining the concentrations of dehydroepiandrosterone (DHEA), androstenedione (Delta(4)A), testosterone (T), estrone (E(1)), and 17beta-estradiol (E(2)) in peripheral and spermatic venous plasma samples from 14 normal men and 5 men with unilateral testicular atrophy. Four normal men and one patient with unilateral atrophy of the testis were given human chorionic gonadotropin (HCG) before surgery. Plasma estrogens were determined by radioimmunoassay; plasma androgens were measured by the double-isotope dilution derivative technique. Peripheral concentrations of these steroids before and after HCG were similar in both the normal men and the patients with unilateral testicular atrophy. In normal men, the mean +/-SE spermatic venous concentrations were DHEA, 73.1+/-11.7 ng/ml; Delta(4)A, 30.7+/-7.9 ng/ml; T, 751+/-114 ng/ml; E(1), 306+/-55 pg/ml; and E(2), 1298+/-216 pg/ml. Three of four subjects with unilateral testicular atrophy had greatly diminished spermatic venous levels of androgens and estrogens. HCG treatment increased the testicular secretion of DHEA and T fivefold, Delta(4)A threefold, E(1) sixfold, and E(2) eightfold in normal men. In the single subject with an atrophic testis who received HCG, the spermatic venous concentrations of androgens and estrogens were much less than in normal men similarly treated. We conclude that: (a) E(1) is secreted by the human testis, but testicular secretion of E(1) accounts for less than 5% of E(1) production in normal men; (b) HCG stimulation produces increases in spermatic venous estrogens equal to or greater than the changes in androgens, including testosterone; and (c) strikingly decreased secretion of androgen and estrogen by unilateral atrophic human tests cannot be appreciated by analyses of peripheral steroid concentrations.

On the Mechanism of the Anti-androgenic Action ofFlutamide (α-α-α-Trifluoro-2-methyl-4'-nitro-m-propionotoluidide)in the Rat

Abstract: The effect of [α-α-α-trifluoro-2- methyl-4'-nitro-m-propionotoluidide], flutamide, on 3H-testosterone and 3H-dihydrotestosterone uptake and metabolism in rat ventral prostate and semial vesicle has been studied and compared to cyproterone acetate. Testosterone-treated castrated rats were given an oral dose of 15 mg/kg of either drug for 3–7 days; neither agent suppressed 3H-testosterone uptake by the tissue at 60 min following an intraperitoneal injection of the labeled steroid given 24 hr after the last dose of drug. Both, however, fully antagonized the effect of testosterone on maintaining prostate and seminal vesicle weights in these rats. In contrast to these results both flutamide and cyproterone acetate, administered p. o. at IS mg/kg/4 days, markedly inhibited 3H-testosterone uptake and retention by prostate and prostate nuclei when labeled androgen was given 3 hr following the last dose of the drug. Similarly, a single dose of these drugs co-administered via ip injection with either 3H-testosteron...

Two pools of luteinizing hormone in the human pituitary: evidence from constant administration of luteinizing hormone-releasing hormone.

Abstract: The pituitary gonadotrophin response to constant intravenous infusions of hypothalamic luteinizing hormone-releasing hormone (LH-RH), 0.2 μg/min for 4 hr, was studied in 5 normal human men. Serum LH-RH levels were measured by radioimmunoassay to confirm the constancy of the infusions. Serum luteinizing hormone levels in response to the constant LH-RH administration revealed a biphasic pattern of elevation characterized by early and late peaks. This pattern of release is similar to that of other hormones stored in granules and suggests the existence of two pools of luteinizing hormone in the human pituitary, one requiring longer LH-RH stimulation for release than the other. In contrast, serum follicle-stimulating hormone values revealed a gradual rise during the entire infusion.

Androgen receptors in mouse kidney: a study of male, female and androgen-insensitive (tfm-y) mice

Abstract: In vivo and in vitro androgen binding was studied in kidneys from male, female, and androgen-intensive (tfm/y) mice using sucrose gradient and dextran-coated charcoal assays The mouse kidney differs from prostate in that it has very low 5a-reductase activity and, as a consequence, very little testosterone is converted to dihydrotestosterone Following iv administration of 3H-testosterone, the unmetabolized steriod was bound by a 79S cytoplasmic and a 36S nuclear macromolecule In vitrostudies indicated that this testosterone “receptor” complex in cytosol from castrated males hada Kd of 17 × 1O-9M binding 56 × 10-14 moles/mg cytosol protein Similar values were obtained using cytosol from intact males and females The protein nature and heat lability of the receptor and the need for cysteine groups for binding activity was demonstrated The cytosol receptoralso bound 3H-dihydrotestosterone but with an apparent lesser affinity than for testosterone Testosterone, dihydrotestosterone, androstenedione an

New evidence for the role of the Sertoli cell and spermatogonia in feedback control of FSH secretion in male rats.

Abstract: A study is presented evaluating the effect of selective germ cell depletion on regulation of plasma FSH concentrations in chronic vitamin A-deficient (VAD) male rats. Plasma FSH, LH and testosterone levels were measured to assess pituitary-testicular interaction and the specific activities of certain testicular enzymes were determined to evaluate seminiferous tubular function during genii cell reduction. By 130 days, the testicular effects of vitamin A deficiency were maximal and resulted in loss of all germinal elements beyond spermatogonia. However, Sertoli cells andLeydig cells appeared normal. Notably in the presence of an intact pituitary-testicular axis, as judged by a normal response to castration, plasma FSH levels in VAD rats were indistinguishable from age matched controls. Although plasma testosterone levels in VAD rats were significantly lower than normals, this was associated with a reduction in plasma LH as well. The physiologic significance of decreased androgen levels is not clear. At appr...

Synandrogenic and Antiandrogenic Effect of Progestins: Comparison with Nonprogestational Antiandrogens

Abstract: Preliminary studies indicated that low doses of cyproterone acetate (Cyp Ac) potentiated the action of testosterone on mouse kidney. This unexpected observation prompted a more extensive evaluation of several progestins (progesterone, progesterone caproate, Cyp Ac, medroxyprogesterone acetate and megestrol acetate) as well as nonprogestational antiandrogens (flutamide, BOMT, cyproterone). The effects of these agents, both alone and in combination with testosterone, on the kidney arid male reproductive tract of the mouse were determined. Testosterone (0.1 mg/day) resulted in a 2- to 5-fold increase in kidney β3-glucuronidase activity after 6 days of treatment. Of the progestins tested, only medroxyprogesterone acetate (MPA) and megestrol acetate stimulated β-glucuronidase in the kidney. Androgen-insensitive (tfm/y) mice with defective androgen receptors did not respond to high doses of MPA, suggesting that androgens and progestins share a common mechanism of action on kidney. With the exception of progeste...

The Conversion of Androgens to Estrogens in Hyperthyroidism

Abstract: To investigate the mechanism of the increased plasma estradiol levels in spontaneous hyperthyroidism, the contribution, by peripheral conversion, of androstenedione and testosterone to the circulating estrogens was determined. The conversion ratio of androstenedione to estrone was significantly increased in both males and females (0.0396 and 0.0256, respectively). The conversion ratio of androstenedione to estradiol was increased in the male (0.0094) but not in the female (0.0051) patients. The conversion ratio of testosterone to estrone was increased in both males (0.0072) and females (0.0070). The conversion of testosterone to estradiol, however, was not increased in either sex. The plasma concentration of androstenedione was significantly increased (0.34 μg/100 ml) in the male patients with hyperthyroidism. However, the production rate of androstenedione was increased in both sexes (8.59 and 6.72 mg/day). The contribution of testosterone and androstenedione to plasma estrone and estradiol (pro...

Hypogonadism induced by a transplantable, prolactin-producing tumor in male rats: hormonal and morphological studies.

Abstract: Pituitary tumors originating from clonal strains of GH1B1 and GH12C1 cells differ mainly in the quantities of prolactin production. After these tumors were transplanted to Wistar- Furth inbred rats, only the male rats bearing GH1B1tumors which secreted high amount of prolactinand growth hormone exhibited growth retardation and genital atrophy. Female rats bearing the same strain of GH1B1 tumor and male rats bearing the predominantly growth hormone-producing GH12C1 tumor were not similarly affected. As compared to the control and GH12C1 tumorbearing animals, the male rats with GH,B! tumors had strikingly higher levels of circulating prolactin, moderately elevated levels of estrogen and luteinizing hormone but extremely low levels of testosterone. Histological studies of the atrophic testes and accessory sexual glands of the GH1B1 tumorbearing rats confirmed the hypoandrogenism foundin these animals. The hormonal data strongly suggest that hyperprolactinemia derived from tumor source was responsible for the...

Effect of active immunization to luteinizing hormone releasing hormone on serum and pituitary gonadotrophins, testes and accessory sex organs in the male rat.

Abstract: The effects of active immunization to luteinizing hormone releasing hormone (LH-RH) on serum and pituitary gonadotrophins testes and accessory sex organs in the male rat were studied. 6 rats were immunized with synthetic LH-RH and 6 rats served as controls. 12 weeks postimmunization animals were bled and the presence of antibody was determined by radioimmunoassay. Immunoreactive LH and follicle-stimulating hormone (FSH) in pituitary extracts and in serum were measured by double-antibody radioimmunoassay. The immunized rats showed atrophy of the testes and secondary sex organs and they had antibodies in the circulation 12 weeks postimmunization. Serum LH was not detectable in any of the antibody producers and pituitary LH was 1/3 that of the controls. Pituitary FSH in the LH-RH antibody producers was 1/4 that of controls and serum FSH was barely detectable (100-120 ng/ml compared with 313-545 ng/ml in controls). Serum testosterone in immunized rats was .28 ng/ml compared with 3.29 ng/ml in controls. Histological studies revealed a total arrest of spermatogenesis in the immunized rats. It was concluded that antibodies to LH-RH can inhibit the action of indogenous hormone and that LH-RH is the releasing hormone required for release of LH and FSH in the rat.

Virilization of the Wolffian Duct in the Rat Fetus by Various Androgens

Abstract: To assess the capacity of different androgens to virilize the urogenital tracts of female rat embryos, pregant rats were given varying amounts of ten steroids from day 14 of gestation until day 21. The newborn from these mothers were given 1/25 of the maternal dosage on days 1 and 3 after birth and killed on day 4. The urogenital tracts of the female embryos were assessed for the presence of the epididymis, vas deferens, seminal vesicle, and prostate. Dihydrotestosterone administration invariably produced bilateral virilization of the female urogenital tract when the maternal dosage was 8 mg/day, whereas methyltestosterone, methyldihydrotestosterone, and 3α, 17β-androstanediol produced equally marked masculinization at a 4 mg/day dosage. No virilization was noted following treatment with 5β-dihydrotestosterone, androstenedione, 3β,17β-androstanedione, or androsterone. Testosterone in these dosages caused fetal resorption. These findings, considered together with recent studies of androgen metabolism and b...

Masculinization of rat liver enzyme activities following hypophysectomy.

Abstract: The metabolism of 5α-[4-I4C]androstane-3α,17β-diol and 4-[4-l4C]androstene-3,17-dione was studied in the microsomal fraction and that of 4-[4-l4C]androstene-3,17-dione also in the 105,000 × g supernatant fraction of livers from male and female rats that had been castrated or castrated and hypophysectomized. The microsomal metabolism of 5α-[4-14C]androstane-3α,17β-diol was also studied in livers from hypophysectomized rats treated with testosterone propionate or estradiol benzoate. Hypophysectomy led to an overall masculinization of hepatic steroid metabolism in female rats (increased activities of the 2α-,2β-,7β- and 18-hydroxylase systems active on 5α-androstane-3α,17β-diol and of the 6β- and 16α-hydroxylase systems, 3β- and 17α-hydroxysteroid reductase and 5β-reductase enzymes active on 4-androstene-3,17-dione). These findings indicate the existence of (a) hypophyseal feminizing factors) that feminize(s) the basic masculine character of the hepatic sex-dependent enzyme activities. On the other hand, the...

Androgen receptors in a Syrian hamster ductus deferens tumour cell line

Abstract: WE have established in culture a cloned line of hamster ductus deferens cells that contains a saturable, high affinity testosterone receptor protein. These cells exhibit an increased rate of DNA synthesis in response to testosterone and 5α-dihydrotestosterone (DHT) treatment, although they probably do not require either androgen for survival. We believe this is the first description of a cloned cell line that exhibits a growth response to a physiological dose of androgen. The mechanism of action of the steroid may be similar to that in the normal tissue of origin.

Submaxillary gland epidermal growth factor: a sensitive index of biologic androgen activity.

Abstract: The increase in immunoreactive epidermal growth factor (EGF) concentrations in the submaxillary glands of female Balb/C mice was evaluated as a bioassay for androgenic steroids. A simple, sensitive, and specific radioimmunoassay was used to measure EGF. Testosterone and dihydrotestos-terone, injected subcutaneously in a dose of 2 mg per day, increased EGF after only 1 day. An exponential rise in EGF was observed between days 1 to 5. EGF concentrations increased more slowly from days 7 to 14. The dose-response relationship for testosterone was linear over a 300-fold dose range, and was parallel to that of dihydrotestosterone, which was 13.4 times more potent than testosterone. 3±-An-drostane- diol and 3²-androstane-diol generated steeper dose-response curves. Their potencies rela-tive to testosterone, based on a median response, were 5.0 and 0.07, respectively. The submaxillary gland EGF levels of androgen-insensitive (tfm/y) mice failed to increase in response to high doses of a long-acting testosterone p...