Showing papers on "Testosterone published in 1969"

Conversion of blood androgens to estrogens in normal adult men and women

Abstract: Continuous infusions of Delta(4)-androstenedione-7-(3)H and testosterone-7-(3)H have been used to demonstrate that these androgens are converted to estrone and 17beta-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [chi(-PRO)] and free precursor steroid [chi(-PRE)], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [rho](BB) (AE1), for androstenedione conversion to estrone ([rho](BB) (AE1) = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [rho](BB) (TE2), for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [rho](BB) value are greater in males than females. For the androgen interconversions, [rho](BB) (AT) is 4.5% in males and 2.2% in females; [rho](BB) (TA) is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03.

A comparative study of the conversion of testosterone to 17-beta-hydroxy-5-alpha-androstan-3-one (Dihydrotestosterone) by prostate and epididymis.

Abstract: The conversion of testosterone-1,2-3H to dihydrotestosterone-3H has been measured under standardized conditions in slices of various tissues from 11 species. In the rat, the highest rates of this conversion were observed in prostate, epididymis, seminal vesicle, penis, preputial gland and scrotum, the other tissues exhibiting much lower values. When the rate of dihydrotestosterone formation was compared in prostate from 9 species, the values observed varied from 569±69 μμmoles/100 mg tissue in the rat to immeasurably low levels in the bull (4±3 μμmoles/100 mg/hr), whereas this conversion was demonstrable in all epididymal tissues studied. Furthermore, dihydrotestosterone formation was measurable in all of the immature prostates studied, including that from calf, and in a variety of other tissues known to be under androgenic control—duck preen gland, the comb and wattle of the chicken, and the preputial gland of rat and mouse. Dihydrotestosterone formation was not demonstrated in any muscle tested...

Studies of the pituitary-Leydig cell axis in young men with hypogonadotropic hypogonadism and hyposmia: comparison with normal men, prepuberal boys, and hypopituitary patients.

Abstract: Pituitary and gonadal function was studied in seven chromatin-negative men, ages 15-27 yr, with retarded sexual and somatic development, skeletal anomalies, and hyposmia. These hyposmic patients were compared with normal men, prepuberal boys and hypogonadal patients with hypopituitarism. The urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels of hyposmic subjects were the same as those of normal boys and hypopituitary patients but significantly lower than those of normal men. Clomiphene citrate did not cause an increase in plasma FSH and LH levels in either hypogonadal group as it does in normal men. In contrast to hypopituitary patients, thyroid and adrenocortical function and release of growth hormone in the hyposmic subjects were normal. The plasma testosterone levels were equally low in prepuberal, hypopituitary, and hyposmic patients but were increased to a greater extent by human chorionic gonadotropin (HCG) treatment in prepuberal and hypopituitary subjects than in the hyposmic patients. Prolonged treatment with HCG has failed to return plasma testosterone levels to normal in two hyposmic patients. These observations suggest that there are defects of both pituitary and Leydig cell function in men with the syndrome of hypogonadism, skeletal anomalies, and hyposmia. They have impaired secretion of FSH and LH and a Leydig cell insensitivity to gonadotropin.

INHIBITION BY STEROIDS OF PARATHYROID HORMONE-INDUCED Ca45 RELEASE FROM EMBRYONIC RAT BONE IN VITRO

Abstract: In vitro effects of several steroid hormones and cholesterol on bone resorption were examined in tissue culture. Embryonic rat long bones were prelabeled with Ca 45 . Bone resorption was produced with parathyroid hormone and was quantified as release of Ca 45 from the paired bones. Steroids were added over a 10 -9 to 10 -3 M concentration range. All of the steroids at the highest concentrations tested (10 -5 -10 -3 M) inhibited the response to parathyroid hormone. At these concentrations several steroids also inhibited Ca 45 release in the absence of parathyroid hormone. At intermediate concentrations (1.5 x 1O -8 to 10 -6 M), hydrocortisone, corticosterone, testosterone and cholesterol all showed some inhibition. At concentrations less than 1.5 x 10 -8 M, only dexamethasone was inhibitory. The inhibition produced by dexamethasone could be antagonized by increasing the concentration of parathyroid hormone. The results indicate that, at concentrations achieved in vitro , glucocorticoids can inhibit bone resorption by a direct effect on bone. In addition, the results suggest that the in vitro inhibition of bone resorption produced by steroid hormones at high concentrations is a nonspecific effect.

Changing sensitivity of the pubertal gonadal hypothalamic feedback mechanism in man.

Abstract: Clomiphene citrate in doses which stimulate gonadotropin production in the adult suppresses urinary follicle stimulating hormone (FSH) excretion and plasma testosterone concentration in prepubertal children. Such results indicate that feedback between gonad and hypothalamus is operative and highly sensitive in prepubertal humans. Puberty in man, as in the rat, is accompanied by a decrease in the sensitivity of the feedback mechanism.

Levels of testosterone, androstenedione, estrone and estradiol-17 beta in the testes of fetal sheep.

Abstract: Testosterone, androstenedione, estrone and estradiol-17β were determined in the testes of fetal sheep ranging in age from 30 to 132 days of intrauterine life These steroids were measured by micromethods using gas-liquid chromatography with electron capture detection The presence of testosterone and androstenedione was demonstrated in the fetal testis on the 30th day of gestation, 5 days before onset of sexual differentiation and the earliest period studied The amounts of testosterone and androstenedione were similar in 46- to 65-day-old testes, while the levels of testosterone were much higher than those of androstenedione at the 30th and 35th days and after the 65th day of intrauterine life Detectable amounts of estrone were present in 70-day-old testes (Endocrinology 85: 280, 1969)

In Vivo Effect of Sex Hormones on the in Vitro Synthesis of Prolactin and Growth Hormone in Normal and Pituitary Tumor-Bearing Rats

Abstract: The in vivo effects of hormone-secreting pituitary tumors MtTW5, StW5 and 7315a on the in vitro synthesis of prolactin and growth hormone by rat pituitary gland have been studied. The in vitro incorporation of leucine-4,5-3H into these hormones of male and female rats was followed by subjecting homogenates of the pituitary glands and the incubation medium to polyacrylamide gel electrophoresis. Transplantation of 7315a, a prolactin- and ACTH-secreting tumor; MtTW5, a prolactin- and growth hormone-secreting tumor; or StW5, a growth hormone-secreting tumor, into intact female or male rats, caused a decrease in the incorporation of leucine-4,5-3H into prolactin. This decrease in prolactin synthesis was promptly reversed by administration of polyestradiol phosphate to tumor-bearing rats. The labeling of prolactin was also greatly stimulated in intact and castrated nontumor rats by the administration of estrogen and testosterone, while 17α-hydroxyprogesterone caproate injection was without effect. The incorpora...

Antagonistic Action of Anti-androgens on the Formation of a Specific Dihydrotestosterone-Receptor Protein Complex in Rat Ventral Prostate

Abstract: Cyproterone (1,2α-methylene-6-chloro-Δ4,6-pregnadien-17α-ol-3,20-dione) 17α-acetate, a potent anti-androgen, suppressed the uptake of radioactive androgens in vivo by the ventral prostate of rats. This was accompanied by a decrease in the retention of 5α-dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) by prostate cell nuclei . Cyproterone and its 17α-acetate (less than 0.5 µg/ml) also inhibited the formation of a specific dihydrotestosterone-protein complex in prostate cell nuclei when minced prostate was incubated with radioactive testosterone or dihydrotestosterone. Estradiol-17β, diethylstilbestrol, and progesterone, but not hydrocortisone succinate, also suppressed the retention of dihydrotestosterone by prostatic cell nuclei in vitro, but to a much lesser extent than cyproterone.

Induction and Facilitation of Female Mating Behavior in Rats Treated Neonatally with Low Doses of Testosterone Propionate

Abstract: Neonatal injections of 10 μg testosterone propionate (TP) lowered the sexual responsiveness of the adult female rats to progesterone. Females were injected on day 1, 2, 4, 6 or 10 of life with 10 μg TP. As adults these females were spayed and tested for female sex behavior under 3 conditions: 1) following pretreatment with estradiol benzoate (EB); 2) following pretreatment with EB and progesterone; 3) following pretreatment with EB and progesterone and a 2 hr period of adaptation to the test arena prior to the behavior test. Sexual behavior was measured by placing the female with a vigorous male until he mounted her 50 times; the ratio of lordoses to mounts was used as the measure of sexual responsiveness. Neonatal injections of 10 μg TP did not lower responsiveness to estrogen alone. In fact, for those females which received an injection of TP on day 1, 2 or 4 of life, sensitivity to estrogen appeared to be increased. The lordosis response level following estrogen and progesterone pretreatment was suppre...

Serum gonadotropin and testosterone levels in uremic males undergoing intermittent dialysis

Abstract: Twenty-six adult males with uremia due to chronic renal disease were studied to determine the circulating levels of gonadotropins. In some of these patients serum testosterone levels were also measured. Patients receiving intermittent hemodialysis had higher levels of luteinizing hormone (LH) than normals, uremic patients not receiving dialysis and patients on peritoneal dialysis. Serum testosterone levels tended to be low in uremic patients. No significant alterations in follicle-stimulating hormone (FSH) were observed in the groups studied. Uremia seems to effect Leydig cell function without producing an associated rise in gonadotropins with the exception of an increase in LH in patients on intermittent hemodialysis.

Effect of hyperthyroidism and hypothyroidism on the metabolism of testosterone and androstenedione in man.

Abstract: The plasma concentration, metabolic clearance (MCRT) and plasma production rates of testosterone, the metabolic clearance rates of androstenedione (MCRA), the conversion ratios and rate transfer constants of these steroids were studied in hyperthyroidism and hypothyroidism. In hyperthyroidism there occurred a significant decrease in both the MCRT and conversion ratio of testosterone to androstenedione. These changes were associated with an increased plasma level of testosterone in both sexes resulting in a normal plasma production rate of the androgen. The MCRA and MCRA/m2 in hyperthyroidism was not significantly different from normal. However, the conversion ratio of androstenedione to testosterone was significantly increased in this disorder. The rate transfer constants of testosterone and androstenedione were unchanged from normal. Following return to the euthyroid state the values returned to normal. Hypothyroidism was associated with an increased MCRT, MCRT/m2 and conversion ratio of testost...

Androgen Accumulation and Binding to Macromolecules in Seminal Vesicles: Inhibition by Cyproterone

Abstract: Cyproterone reduces the accumulation of testosterone and dihydrotestosterone in seminal vesicles 30 minutes after intravenous administration of tritiated testosterone to castrated rats. Testosterone, added in vitro, binds to macromolecules from the supernatant fraction of the seminal vesicle homogenates; this interaction is antagonized competitively by cyproterone. Cyproterone may diminish androgenic effects by competition for binding molecules.

Effects and metabolism of hormones in normal and neoplastic prostate tissue.

Abstract: Publisher Summary This chapter discusses the effects and metabolism of hormones in normal and neoplastic prostate tissue. The chapter focuses on recent work on fine structure of prostate tissue, hormonal influences on the metabolism of specific glandular constituents, the effect of hormones on viable prostate tissue in culture and on prostatic steroid catabolism, and a discussion of human prostatic neoplasia and its rodent and canine counterparts. It is now becoming apparent that the maintenance of normal prostatic structure and function and of residual epithelial activity in the castrate depends on the complex competitive or synergistic action of sex steroids, corticoids, and prolactin on the end organ. “Biological titration” with estrogen–androgen combinations has shown that the administration of both hormones is required to maintain the morphological integrity of the prostatic epithelium and the weight of the gland. Dihydrotestosterone and 5α-androstane-3α,l7 β-diol, the major products of the reductive catabolism of testosterone in the prostate, and their 17-ketosteroid analogs may be the active androgens in the gland.

Regulation by FSH and ICSH(LH) of Reproductive Function in the Immature Male Rat

Abstract: Requirements for FSH and ICSH (LH) in male reproduction have been evaluated in immature rats of the Sprague-Dawley strain; animals were hypophysectomized at 28 days of age and hormone injections initiated 2 months later. Combinations of extensively purified ovine FSH and ICSH of high specific activity established spermatogenesis in the seminiferous tubules of the retrogressed testis, and promoted copious androgen secretion as evidenced by growth of the sex accessory organs. FSH, given together with ICSH, markedly enhanced androgen production. Alone, individual hormones effected only limited development of the seminiferous tubules in these immature animals. FSH stimulated Sertoli cell development but no advance in germ cell maturation. Testosterone stimulated primary spermatocytes to complete meiosis, as did ICSH; with neither hormone did spermiogenesis proceed beyond the early spermatid stage. In individual rats, production of spermatozoa was correlated with high androgen secretion. However, exogenous and...

High-affinity binding of progesterone, testosterone and cortisol in normal and androgen-treated guinea pigs during various reproductive stages: relationship to masculinization.

Abstract: Sera from normal and androgen-treated female guinea pigs were obtained during the estrous cycle, pregnancy and puerperium. They were analyzed for binding affinity toward progesterone, testosterone and cortisol by multiple equilibrium dialysis using radiolabeled steroids. Cortisol levels were also determined. A marked increase in binding activity for all 3 steroids, especially progesterone and testosterone, was found during pregnancy; the cortisol concentration rose concomitantly. By the end of the puerperium all parameters measured had returned toward estrous cycle levels. Testosterone treatment of the cycling females greatly lowered the cortisol-binding activity of the serum as well as the peripheral cortisol values, and resulted in a slight decrease of the binding activity for testosterone. Sera from pregnant guinea pigs receiving testosterone had lower peripheral cortisol levels than the pregnant controls; the binding activity toward progesterone and testosterone was generally greater than in the untre...

Plasma levels of testosterone in male rabbits following copulation.

Abstract: It is well established that the rabbit ovulâtes in response to mating and a marked ovarian release of 20a-hydroxypregnen-4-en-3-one will occur shortly after coitus in this species (Hilliard, Archibald & Sawyer, 1963). This change in progestin secretion following mating corresponds with the increase of gonado¬ trophin in peripheral blood (Hilliard, Hayward & Sawyer, 1964), and the release of interstitial cell stimulating hormone (icsh) and prolactin from the pituitary gland (Desjardins, Kirton & Hafs, 1967). Moreover, Taleisnik, Caligaris & Astrada (1966) noted a decrease in pituitary content of icsh and an increase in plasma icsh in female rats following copulation. The level of ascor¬ bic acid in the ovary of these animals was lower than in control rats. The hormonal response of the male gonad to copulation is less overt and has received little attention. Copulation will increase the blood levels of icsh and decrease the pituitary concentration of the hormone in the male rat (Taleisnik et al., 1966). The secretion of androgenic steroids into the spermatic venous blood of anaesthetized rabbits appears to increase shortly after coitus (Endroczi, 1962) and this increase is not found in male rabbits with hypothalamic lesions. Since testosterone is the major androgen secreted by the male gonad, it was deemed important to study fluctuations of this hormone in the peripheral blood of the rabbit following coitus.

Effects of the Anti-androgen Cyproterone Acetate on Mating Behavior and Seminal Vesicle Tissue in Male Rats

Abstract: The synthetic steroid cyproterone acetate (6-chloro-17-hydroxy-lα,2α-methylenepregna- 4,6-diene-3,20-dione acetate) exerts strong antiandrogenic properties with respect to the seminal vesicles, but not with respect to androgen dependent mating behavior in male rats. Gonadectomized, sexually experienced male rats were treated with 1) testosterone propionate (TP); 2) TP plus cyproterone acetate, or 3) oil for 3 weeks, and given 3 mating tests at weeklyintervals. The seminal vesicles of all males were removed after 2 weeks of treatment. The intensity of mating behavior declined progressively in the oil treated castrates but not the androgen or androgen plus anti-androgen treated males. The seminal vesicles of the oil treated and androgen plus anti-androgen treated rats regressed in comparison with the seminal vesicles of males treated only with testosterone. (Endocrinology 84:155, 1969)

Uptake and metabolism in vivo of testosterone-1,2-3H by accessory sex organs of male rats; influence of some hormonal compounds.

Abstract: A study was made of the influence of certain hormones and synthetic hormonal compounds on the uptake of radioactivity by rat seminal vesicles and prostate gland following the administration of testosterone-l,2-3H in vivo. Androstenedione, 17β-methyltestosterone, 17βmethyl-β-nortestosterone (SK & F 7690), progesterone and corticosterone reduced the uptake of radioactivity. 17β-Estradiol and diethylstilbestrol did not reduce the uptake; indeed, in the lateral prostate an increased accumulation of radioactivity was observed. One hr after administration of testosterone-3H, unchanged testosterone represented 3.0–17.1& of the total radioactivity in the accessory sex organs. 5a- Androstan-17β-ol-3-one was the main metabolite, constituting about 70% of the total radioactivity. (Endocrinology 85: 683, 1969)

Steroid Biosynthesis by the Equine Testis

Abstract: Enzyme reactions in the stallion testis involved in steroid synthesis were studied to determine the factors which account for the high production of estrogens as well as androgens. In comparison with other species, the stallion testis was found to have lower 17β- (testosterone) dehydrogenase activity and very high 19-(androstenedione) hydroxylase and aromatizing systems. As a consequence, while androstenedione served as a precursor of both testosterone and estrone, a greater proportion was converted to the estrogen. The 19-hydroxylation and aromatizing activities for testosterone seemed lower than those for androstenedione. The 3β-hydroxysteroid dehydrogenase systems for 17-hydroxypregnenolone and dehydroepiandrosterone were very active, but the A6-17,20- lyase system was apparently much less active than the A4-17,20-lyase. The predominant route of biosynthesis seems, therefore, to be: pregnenolone →17-hydroxypregnenolone →17-hydroxyprogesterone →Δ4-androstenedione →19-hydroxy- ↓androstenedione→estrone te...

Plasma and pituitary LH and FSH in the castrated rat following short-term steroid treatment.

Abstract: The effects of short-term steroid treatment on the blood and pituitary LH and FSH levels of previously castrated adult male and female rats were examined, using ovarian ascorbic acid depletion (OAAD) and HCG-augmentation bioassays for LH and FSH activities. Pituitary and plasma FSH activities, 3 days after an injection of 1) testosterone propionate (TP) or 2) estradiol benzoate plus progesterone (E + P), were compared in 5 experiments. Concomitant changes in plasma and pituitary LH levels were studied in 3 of these experiments and 2 others. In 2 further studies in spayed rats, both stored and circulating LH and FSH were examined after 7 days of TP treatment. In addition, pituitary FSH and plasma LH were studied 24 hr after single injections of TP. Both steroid treatments (TP and E + P) decreased plasma LH levels without altering pituitary LH concentrations detectably. The TP effect on plasma LH was evident after only 24 hr. Thus, both treatments apparently reduced the rate of LH release. Because of the re...

Effects of the Anti-androgen Cyproterone Acetate on the Uptake of l,2-8H-testosterone in Neural and Peripheral Tissues of the Castrate Male Rat

Abstract: The anti-androgen cyproterone acetate (CA) causes regression of the seminal vesicle when administered to the mature male rat, and CA treatment of the pregnant rat permits vaginal development in male offspring. CA, however, does not inhibit androgen controlled sexual behavior in male rats. It was therefore hypothesized that CA might inhibit the uptake and retention of l,2-3H-testosterone in peripheral genital tissues, but not in central neural tissues which mediate mating behavior. To test this hypothesis, castrate males were administered tritiated testosterone following pretreatment with CA or oil and sacrificed 5 or 60 min after testosterone treatment. All tissue samples showed androgen uptake. CA had no influence on uptake measured at 5 min. In pituitary, brain and muscle, radioactivity levels were lower in the 60 min samples than in the 5 min samples. CA had no effect upon retention of testosterone measured at 60 min in these tissues. Radioactivity levels were the same or higher at 60 min in the semina...

Metabolism of testosterone and androstenedione in normal and ovariectomized women

Abstract: Metabolic clearance rates of testosterone (MCRT) and androstenedione (MCRA) were determined twice during the same cycle in six normal women, using a constant infusion of testosterone-3H and androstenedione-14C Nonlabeled steroids served as internal standards Plasma concentrations of testosterone (iT) and androstenedione (iA) were measured, and the blood production of testosterone (PBT) and of androstenedione (PBA) were calculated The interconversions of these two steroids were also estimated Six ovariectomized women were studied in the same manner For testosterone, the mean iT in the normal women was not significantly different from that in the ovariectomized subjects, whereas the MCRT and PBT were significantly lower in the ovariectomized subjects For androstenedione, the mean MCRA values of the two groups of subjects were not different, whereas the iA and PBA in the normal women were about double those in the ovariectomized subjects In comparing the follicular and luteal phases of the menstrual cycle in four of six subjects there was no difference in iT, MCRT, or PBT, whereas iA, MCRA, and PBA were increased in the luteal phase In one ovariectomized woman infused with testosterone and androstenedione at physiologic levels, MCRT doubled but MCRA remained the same After six wk on estrogen, the same subject did not show any change in MCRT after infusion of testosterone It is suggested that MCRT depends on PBT and on plasma binding of testosterone which is partly estrogen dependent

Secretion of neutral steroid sulfates by the human testis.

Abstract: The monosulfates of testosterone, androsterone, epiandrosterone, dehydroepiandrosterone, androst-5-ene-3β,17β-diol, pregnenolone, pregn-5-ene-3β,20α-diol, and pregn-5-ene-3β,17α,20α-triol and the disulfates of androst-5-ene-3β,17β-diol and pregn-5-ene-3β,20α-diol in the spermatic vein and peripheral blood plasma were quantified. The results show that, in normal subjects, testosterone sulfate, pregnenolone sulfate and possibly androst-5-ene-3β,17β-diol monosulfate are secreted by testis tissue.