SEARCH · PubMed Health

Results for “testosterone”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources

PubMed1996

Pretreatment with phorbol ester and an LHRH agonist reduces testosterone production and protein kinase C activity in rat Leydig cells challenged with PDBu and LHRH.

We have investigated the role of protein kinase C (PK-C) in luteinizing hormone-releasing hormone (LHRH)-induced testosterone secretion from purified rat Leydig cells (70-80-day old Sprague-Dawley rats) by pretreating the cells in vitro with 200 mM phorbol 12,13-dibutyrate (PDBu) (a known procedure to down-modulate this enzyme in most cell types) and 1 muM [D-Ala6,Des-Gly10]-LHRH ethylamide, an LHRH agonist (LHRH-A). Following pretreatment we measured PK-C activity and secretion of testosterone in response to subsequent challenges with the PK-C activator PDBu (20-2000 nM) and with LHRH (0.001-1.0 muM) and the Ca(2+)-mobilizing secretagogue A23187 (0.1-100 microM) in the same cell preparation. PDBu and LHRH-A pretreatments caused a reduction in testosterone secretion in response to subsequent exposure to PDBu or LHRH. Both pretreatments decreased PK-C activity in crude and purified extracts of the same cells. The magnitude of reduction of the secretory response was greater than that of enzyme activity for both PDBu and LHRH-A pretreatment (68.9% reduction of testosterone secretion vs 54.7% reduction of PK-C activity in PDBu-pretreated cells and 78.6% reduction of testosterone production vs 36.6% reduction of PK-C activity in LHRH-A-pretreated cells). The effect of phorbol ester pretreatment on PDBu- or LHRH-stimulated testosterone secretion and PK-C activity was specific (no measurable effect with 4 alpha-PDBu, an inactive phorbol ester). While PDBu and LHRH-A pretreatment reduced Leydig cell responsiveness to PDBu or LHRH, the secretion of testosterone in response to the Ca2+ -mobilizing secretagogue A23187 was similar in PDBu- and LHRH-A-pretreated and in control (non-pretreated) cells. We conclude that down-modulation of protein kinase C by prolonged exposure of Leydig cells to phorbol esters or LHRH-A results in decreased PK-C activity and testosterone secretion. These results provide the first evidence that pretreatment with LHRH-A, which does not enter the cell, can affect the steroidogenesis and PK-C activity responses to PDBu (the intracellular ligand of PK-C).

Animals↗

PubMed1998

Salivary testosterone in postmenopausal women with rheumatoid arthritis.

OBJECTIVE: To study changes in testosterone concentrations in saliva and total testosterone, free testosterone, and sex hormone binding globulin (SHBG) concentrations in serum in 2 groups of postmenopausal women with rheumatoid arthritis (RA), one group with glucocorticoid treatment and the other without it. METHODS: The above mentioned hormonal levels were measured in 20 postmenopausal women with RA undergoing glucocorticoid treatment, in 24 postmenopausal women with RA without treatment, and in 36 postmenopausal women without RA. RESULTS: We observed significantly lower levels of total testosterone in serum, SHBG in serum, testosterone in saliva, and the free testosterone index in the group of patients with RA undergoing glucocorticoid treatment compared to the group without treatment. We did not observe changes in free testosterone concentrations in serum of the groups studied, which is believed due to its lower specificity. CONCLUSION: Testosterone in saliva is a useful indicator for monitoring androgenic status in women with RA.

Aged↗

PubMed1998

Influence of N-methyl-N-nitrosourea, testosterone, and N-(4-hydroxyphenyl)-all-trans-retinamide on prostate cancer induction in Wistar-Unilever rats.

The influence of chemical carcinogen, hormonal stimulation, and chronic dietary administration of the synthetic retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), on the induction of prostate cancer in male Wistar-Unilever rats was determined. Three different tumor induction regimens were used: (a) a single i.v. dose of 50 mg of N-methyl-N-nitrosourea (MNU) per kg body weight, followed by chronic androgen stimulation via s.c. implantation of two silastic capsules containing 40 mg testosterone each; (b) a single i.v. dose of 50 mg of MNU per kg body weight (no testosterone treatment); and (c) chronic androgen stimulation with implanted testosterone capsules (no MNU treatment). In a fourth series of animals, the incidence of spontaneous prostate tumors was determined in groups of rats receiving neither carcinogen nor hormone stimulation. Within each series, parallel groups of animals were fed a control (vehicle-supplemented) diet or control diet supplemented with 4-HPR beginning 1 day after carcinogen administration; retinoid administration was continuous until termination of the study at 450 days. The incidence of accessory sex gland cancer in rats treated sequentially with MNU + testosterone was >60%, in comparison with cancer incidences of <20% in rats receiving MNU only and <5% in rats treated with testosterone only. No spontaneous accessory sex gland tumors were observed in rats receiving no carcinogen and no testosterone. Tumor induction in the accessory sex glands by MNU + testosterone was relatively specific for the prostate: the incidence of carcinoma of the dorsolateral/anterior prostate was more than 5-fold greater than the incidence of cancer present only in the seminal vesicle. 4-HPR conferred no protection against cancer induction in the prostate by any regimen of MNU and/or testosterone. These results demonstrate the importance of both carcinogen exposure and hormone stimulation on the induction of neoplasia in the prostate of Wistar-Unilever rats.

Animals↗

PubMed1998

Micropenis in hypogonadotropic hypogonadism: response of the penile androgen receptor to testosterone treatment.

PURPOSE: We determine whether testosterone therapy alters penile androgen receptor expression within the hypogonadotropic hypogonadal (HPG) micropenis. MATERIALS AND METHODS: In protocol 1 a strain of mice with micropenis due to congenital HPG and wild type litter mates were divided into testosterone treated and untreated groups. Treatment was initiated on day 15 of life. On day 90 of life (day 75 of treatment) the mice were sacrificed, and the penises were removed and weighed. In protocol 2 microphallic mice treated with testosterone were sacrificed on days 0, 6, 30, 60 and 75 after the initiation of treatment. Untreated HPG and wild type litter mates served as controls. At autopsy the penis was removed and weighed, and androgen receptor content was determined by Western immunoblotting. RESULTS: Testosterone treatment resulted in 6-fold up regulation in HPG penile androgen receptor, approximately 1.4-fold higher than in the normal wild type pubescent penis. Testosterone induced and wild type pubescent penile androgen receptor up regulation was maintained for approximately 75 and 60 days, respectively. Despite improved HPG penile androgen receptor expression penile growth did not become normal. Average total penile weight plus or minus standard deviation was 7.2+/-3.5 mg. in untreated HPG mice. Testosterone significantly improved average HPG penile weight to 23.5+/-1.8 mg. (p <0.001). However, the testosterone treated micropenis failed to reach average normal penile size (38.6+/-2.6 mg., p <0.001). CONCLUSIONS: Testosterone increases the concentration and duration of penile androgen receptor expression within the HPG micropenis. Despite this improvement microphallic HPG penile growth does not become normal.

Animals↗

PubMed1998

Restoration of sexual behavior and dopaminergic neurotransmission by long term exogenous testosterone replacement in aged male rats.

PURPOSE: We investigated the effects of long-term testosterone replacement on copulatory behavior and dopaminergic neurotransmission in the medial preoptic area of aged male rats. MATERIALS AND METHODS: The rats were divided into 3 groups depending on testosterone replacement. Those in the long-term replacement group were castrated at the age of 12 months and received testosterone replacement thereafter for 12 months. In the short-term replacement group, rats were castrated at the age of 22 months and high or low dose testosterone replacement was done for 2 months. The control group consisted of aged rats 24 months old and young rats 12 weeks old, neither of which had been castrated or received testosterone replacement. We observed sexual behavior in rats of these groups. After a behavioral test, we measured the tissue concentration of dopamine in the MPOA and the change rate of the extracellular dopamine level induced by infusion of N-methyl-D-aspartic acid (NMDA) in the MPOA and compared the long-term replacement and no-replacement groups. RESULTS: The rats in the long-term replacement group showed a mount rate at the same level as that of young rats at 6 weeks after starting replacement and it was maintained to 24 months of age. Their mount rate was significantly higher than that of the rats with the short-term replacement. A significantly higher change rate of dopamine release was recognized in the long-term group; however, no significant difference in the concentration of dopamine was recognized between aged rats with long-term replacement and those without replacement. CONCLUSIONS: Aged rats (24 months old) with long-term testosterone replacement maintained almost the same level of mount behavior as young rats (12 weeks old). The results imply that long-term testosterone replacement may favorably alter the decline in the process of sexual activity with aging. The restoration by testosterone replacement of dopaminergic activity in the MPOA may be involved in the maintenance of sexual function in aged rats.

Aging↗

PubMed1976

[Studies on endocrine and spermatogenic testicular function. 5. Relationship between dietary protein quality and blood plasma levels of free and bound testosterone in adult rats].

The blood plasma content of testosterone-linking globulins, free testosterone, and total testosterone in 80 adult Wistar rats which received different qualities of feed proteins was determined by means of balancing dialysis and ultracentrifugation, using 3H-testosterone. The first group received casein with four per cent methionine added, the second maize gluten complement with amino acid, and the third casein with methionine and gelatin in a 2:3 ratio, while the fourth group was fed pure maize gluten diet. (Biological valence declined in the given order.) Assays of 100 ml blood plasma of each animal in the first and second groups gave 0.9 mug of testosterone-linking globulins (0.18 mug in third and fourth groups), about 9.0 mug total testosterone (2.5 mug in third and fourth groups), and some 1.4 mug free testosterone (0.55 mug in third and fourth groups). Discussed in this paper is the possible mechanism of regulation by which feed protein quality leads to variation of free testosterone levels in the blood plasma.

Animals↗

PubMed1996

Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot.

Hormonally induced azoospermia induced by weekly im injections of testosterone enanthate provides effective and reversible male contraception, but more practical regimens are needed. Given our previous findings that six 200-mg pellets implanted subdermally produced more stable, physiological T levels and reduced the delivered T dose by more than 50% while maintaining equally effective suppression of sperm output with fewer metabolic side-effects than weekly 200-mg testosterone enanthate injections, we sought in this study to determine 1) whether further dose-sparing could be achieved by lower testosterone doses while maintaining efficacy and 2) the efficacy of adding a depot progestin to a suboptimally suppressive depot testosterone dose as a model depot progestin/androgen combination male contraceptive. Healthy volunteers were randomized into groups (n = 10) who received either of two lower T doses (two or four 200-mg T pellets) or four 200-mg T pellets plus a single im injection of 300 mg depot medroxyprogesterone acetate (DMPA). Two T pellets (400 mg, 3 mg/day) had a negligible effect on sperm output. Four T pellets (800 mg, 6 mg/day) suppressed sperm output between the second to fourth postimplant months; output returned to normal by the seventh postimplant month, although only 4 of 10 men became azoospermic or severely oligozoospermic (< 3 mol/L/mL). The addition of a depot progestin markedly increased the extent, but not the rate, of sperm output suppression, with 9 of 10 becoming azoospermic and 10 of 10 becoming severely oligozoospermic. There were no serious adverse effects during the study. Plasma total and free testosterone levels remained within the eugonadal range at all times with each treatment. Plasma epitestosterone was suppressed by all 3 regimens, consistent with a dose-dependent inhibition of endogenous Leydig cell steroidogenesis. Plasma LH and FSH measured by a two-site immunoassay were suppressed in a dose-dependent fashion by T and further suppressed by the addition of DMPA. Sex hormone-binding globulin levels were decreased by DMPA, but not by either T dose. Prostate-specific antigen and lipids (total, low or high density lipoprotein cholesterol, and triglycerides) were not significantly changed in any group. Thus, a depot testosterone preparation with zero order release must be delivered at between 6-9 mg/day to provide optimal (but not uniform) efficacy at inducing azoospermia. The addition of a single depot dose of a progestin to a suboptimal testosterone dose (6 mg/day) markedly enhances the extent, but not the rate, of spermatogenic suppression, with negligible biochemical androgenic side-effects. These findings provide a basis for the use of a progestin/androgen combination depot for hormonal male contraception.

Adult↗

PubMed1989

Effects of testosterone and 5alpha-dihydrotestosterone on luteal lifespan in dairy heifers.

Endogenous concentrations of testosterone increase approximately 7 d prior to estrus in cattle and goats. Inhibition of testosterone synthesis results in a delay of luteal regression in both species. The purpose of this experiment was to determine if treatment with testosterone or 5alpha-dihydrotestosterone (DHT), 2 to 6 d prior to the endogenous rise in testosterone, would result in premature luteal regression. Sixteen heifers were randomly assigned to one of three treatment groups: 1) Control (n = 6); 2) testosterone (100 mug, n = 5); or 3) DHT (100 mug, n = 5). Each heifer received a single injection of the appropriate steriod on Day 8, 9, 10, 11 or 12 post estrus. Jugular venous blood samples were collected at frequent intervals for 24 h to quantify testosterone, and then daily for 14 d to quantify progesterone. Concentrations of testosterone increased within 15 min of injection of testosterone, and reached a maximum at 30 min. Concentrations were maintained at > 2 ng/ml throughout the first 24 h after injection. Based on concentrations of progesterone, neither androgen had any effect on the lifespan of the corpus luteum or the level of luteal function.

Journal Article↗

PubMed1994

Ratios of serum concentrations of testosterone and progesterone from yearling bulls with small testes.

Thirty crossbred bulls, 12 to 13 mo of age, were used to examine the relationship of testosterone and progesterone concentrations and testosterone: progesterone ratio to measurements of testicular function. Bulls were allotted to 1 of 2 groups based on scrotal circumferences (SC) as follows: the Small SC (n=20) group had scrotal circumference less than 28 cm while the Large SC (n=10) group had scrotal circumference greater than 28 cm. All bulls were administered GnRH (100 mug, im), and blood was obtained immediately prior to injection (t=0), 30 min after injection (t=30) and 2 to 3 h after injection (t=150). Serum was assayed for concentrations of testosterone and progesterone. Semen was evaluated for the percentage of morphologically normal spermatozoa. Testicular parenchyma was sectioned and stained, and 300 cross sections per testis of seminiferous tubules were examined under a light microscope and classified as either active (spermatocytes and spermatids present) or inactive (no spermatocytes or spermatids present). Although progesterone concentrations varied widely (range: 21 pg/ml to 1070 pg/ml), repeated measurements from individual bulls were highly correlated (r(2)=0.74) and did not change significantly (P > 0.1) in response to GnRH treatment. Small SC bulls had a higher percentage of inactive seminiferous tubules (P < 0.001) and a lower percentage morphologically normal spermatozoa (P < 0.001) than Large SC bulls, but no differences in testosterone or progesterone concentrations or in the ratio of testosterone: progesterone were detected. Mean serum testosterone concentration increased (P < 0.0001) by 30 min after GnRH treatment and continued to increase (P < 0.0001) through t=150 but did not differ (p > 0.1) between groups. Normal testosterone secretion in response to GnRH injection suggested that no biochemical lesions in the testosterone production pathway were present in bulls with very small scrotal circumference.

Journal Article↗

PubMedDate not supplied

Serum testosterone levels and reference ranges in reproductive-age women.

OBJECTIVE: To determine the levels of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) in women with no clinical signs of hyperandrogenism and no history of glucocorticoid or oral contraceptive use and to compare these levels with the reference ranges provided by commercial laboratories. METHODS: We undertook a cross-sectional retrospective study of 271 reproductive-age women encountered at an endocrinology clinic for complaints of potential thyroid problems. Serum testosterone and DHEAS levels were determined, and statistical analyses were performed. RESULTS: The serum testosterone level in women with no acne, hirsutism, or menstrual dysfunction was 14.1 +/- 0.9 ng/dL (mean +/- standard error of the mean) (95% confidence interval [CI] = 12.4 to 15.8). This group was considered our study reference population. In women with menstrual dysfunction but no acne or hirsutism, the mean testosterone level was significantly higher (17.9 +/- 1.1 ng/dL; 95% CI = 15.7 to 20.0; P<0.002); with mild hirsutism, it further increased (38.4 +/- 5.1 ng/dL; 95% CI = 27.4 to 49.4; P<0.005); and with moderate to severe hirsutism, it was still higher (49.0 +/- 2.3 ng/dL; 95% CI = 44.4 to 53.6; P<0.003). Serum DHEAS levels showed similar patterns. The upper limit (mean + 2 standard deviations) of testosterone in our study reference population was 28 ng/dL, a level that provided a sensitivity of 84% for detecting hyperandrogenemia. The detection of hyperandrogenemia is essentially impossible when the upper limit of the reference range for testosterone from commercial laboratories (95 ng/dL) is used. CONCLUSION: The testosterone levels reported herein and in the literature for hyperandrogenic women both are within the reference (normal) ranges provided by commercial laboratories. These observations demonstrate why diagnosis of hyperandrogenemia in hyperandrogenic women is difficult when commercial laboratories are used and why this condition is not detected in most affected women. Commercial laboratories should reevaluate the methods used for establishing their reference ranges for serum testosterone.

Journal Article↗

PubMed2000

Melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary-gonadal axis in the rat.

OBJECTIVES: We have investigated the changes in serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone levels together with testicular histology in both pinealectomized (PNX) and intact rats. MATERIAL and METHODS: Twenty-one animals were PNX and allowed to recover for two months. Group I was assigned as PNX, group II PNX+melatonin and group III PNX+Human Chorionic Gonadotropin (HCG). Rats in group IV were sham PNX (S-PNX). An intact group of animals was s.c. injected with melatonin (0.5 mg/kg/day), another group with a combination of melatonin+HCG (5000 IU/kg/day) for seven days. Controls received saline alone (1 ml/kg). At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were determined by Radioimmunoassay, testosterone values by Chemiluminescent Enzyme Immunassay. Testicular tissue was collected and processed for light microscopy. RESULTS: Serum LH levels were increased following PNX, but no such increases were seen in testosterone. In the PNX+melatonin group, serum LH and testosterone values were found to be similar to those of S-PNX group. HCG supplementation to PNX rats resulted in significant decreases in LH (p<0.005), but increased testosterone levels (p<0.001). Melatonin administration to intact animals significantly decreased both LH and testosterone levels (p<0.01). Co-administration of HCG+melatonin resulted in significant decreases in LH (p<0.001) and increases in testosterone levels (p<0.01). Serum FSH values did not show significant changes among groups. Only HCG administration significantly reduced FSH levels (p<0.01). CONCLUSIONS: Our results suggest that melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary axis. There is a functional relationship and feedback regulation between the pineal gland and the testes.

Journal Article↗

PubMed1996

Inhibition of testosterone 5 alpha-reductase: evidence for tissue-specific regulation of thromboxane A2 receptors.

Testosterone has been implicated as a risk factor for cardiovascular diseases and thromboxane A2 (TXA2) may be an important pathophysiologic mediator for them. Testosterone has been shown to increase TXA2 receptor density in several cell types. Testosterone is reduced at the 5 alpha position to its active metabolite, dihydrotestosterone, by 5 alpha-reductase. We determined the effects of epristeride, a 5 alpha-reductase inhibitor, on the density of TXA2 receptors in rat aortic smooth muscle cells and human erythroleukemia cells, a megakaryocyte-like cell, in vitro, and in rat platelets and aortic membranes in vivo. In rat aortic smooth muscle cells, epristeride significantly (P < .01, n = 5) blocked the effect of testosterone to increase TXA2 receptor density (Bmax: 44 +/- 3, 76 +/- 7, 48 +/- 4 and 46 +/- 4 fmol/mg protein, for control cells, cells treated with testosterone (200 nM), cells treated with testosterone and epristeride (10 nM) and cells treated with epristeride, respectively. Epristeride did not block the effect of testosterone in human erythroleukemia cells. Treatment of male rats with epristeride for 2 weeks significantly (P < .01) decreased TXA2 receptor density in aortic membranes (41 +/- 3 for vehicle, n = 10; 27 +/- 3 fmol/mg protein for epristeride, n = 11) but did not significantly change TXA2 receptor density in platelets. Maximum contractile responses of rat aortas to U46619, a TXA2 mimetic, were significantly (P < .001) lower in epristeride-treated rats than in vehicle-treated rats (4.2 +/- 0.1 for vehicle, n = 16, 3.0 +/- 0.2 g tension for epristeride, n = 15). In conclusion, regulation of expression of TXA2 receptors by testosterone in cells of vascular origin, but not in platelets, appears to be via DHT.

5-alpha Reductase Inhibitors↗

PubMed1997

Human cytochrome P450 3A4-catalyzed testosterone 6 beta-hydroxylation and erythromycin N-demethylation. Competition during catalysis.

Cytochrome P450 3A4 is known to catalyze the metabolism of both endogenous substrates (such as the 6 beta-hydroxylation of testosterone) and many important therapeutic agents, including the N-demethylation of erythromycin. However, erythromycin and testosterone have been reported to have little or no effect on the metabolism of each other by recombinant CYP3A4. In an effort to understand the basis of these observations, we studied the N-demethylation of erythromycin and the 6 beta-hydroxylation of testosterone in human liver microsomes and in microsomes from cells containing recombinant human CYP3A4 and P450 reductase under a variety of experimental conditions. In both human liver microsomal and recombinant CYP3A4 systems, erythromycin inhibited testosterone 6 beta-hydroxylation in a concentration dependent manner, and vice versa. However, the inhibition mechanism was complex. At low substrate concentrations, testosterone and erythromycin acted as competitive inhibitors to each other. Under these experimental conditions, an apparent competitive inhibition of testosterone 6 beta-hydroxylation by erythromycin was observed, with Ki values similar to that of the K(m) values for erythromycin. When the rates of testosterone 6 beta-hydroxylation and erythromycin N-demethylation were determined in microsomal incubations containing both substrates at lower concentrations, the observed rates for each reaction were in good agreement with the calculated rates based on the rate equation describing simultaneous metabolism of two substrates by a single enzyme. However, at high substrate concentrations, the kinetic results could be best explained by a mechanism involving partial competitive inhibition. We conclude from these studies that testosterone and erythromycin mutually inhibit the metabolism of each other, consistent with the fact that CYP 3A4 catalyzes the metabolism of both substrates.

Aryl Hydrocarbon Hydroxylases↗

PubMed1979

Testosterone and its precursors and metabolites enhance guanylate cyclase activity.

Both testosterone and cyclic GMP stimulate DNA synthesis. Because cyclic GMP and testosterone seem to have similar actions, the objective of this investigation was to determine if testosterone and its precursors might have part of their mechanism of action through stimulation of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2], the enzyme that catalyzes the formation of cyclic GMP from GTP. The precursors--namely, progesterone, pregnenolone, 17 alpha-progesterone, 17 alpha-hydroxypregnenolone, androstenedione, and dehydroepiandrosterone--caused a 2- to 3 1/2-fold enhancement of guanylate cyclase activity in rat liver, kidney, skeletal muscle, and ventral prostate at a concentration of 1 microM. These precursors are generated from cholesterol, which had no effect itself on guanylate cyclase activity. Testosterone, 19-nortestosterone, 17-methyltestosterone, and 5 alpha-dihydrotestosterone enhanced guanylate cyclase activity 2- to 5-fold in the same tissues at 1 microM. Etiocholanolone, androsterone, and epiandrosterone, metabolites of testosterone metabolism, enhanced guanylate cyclase activity 1 1/2- to 2-fold at this same concentration. Dose-response relationships revealed that testosterone and its precursors and metabolites had their maximal effect at 1 microM but still had some effect at 0.001 microM. The data in this investigation suggest that the guanylate cyclase-cyclic GMP system plays a role in the mechanism of action of testosterone and its precursors.

Animals↗

PubMed2003

Effect of testosterone and season on proenkephalin messenger RNA expression in the preoptic area of the hypothalamus in the ram.

Enkephalin appears to exert an inhibitory action on LH secretion, but whether testosterone regulates enkephalin gene expression is unknown. This study tested the hypothesis that testosterone and/or season modulate preproenkephalin mRNA expression in specific areas of the hypothalamus. Romney Marsh rams were castrated (wethers) either during the breeding season or nonbreeding season and received intramuscular injections of either oil or testosterone propionate (five/group). Blood samples were taken for the assay of plasma LH and testosterone. Preproenkephalin mRNA expression was quantified in hypothalamic sections by in situ hybridization. Mean plasma LH concentrations were reduced and the interpulse interval for LH pulses was greater in testosterone propionate-treated wethers compared with oil-treated wethers, with no change in LH pulse amplitude. Testosterone propionate treatment reduced proenkephalin expression in the diagonal band of Broca, the caudal preoptic area, and the bed nucleus of the stria terminalis. Seasonal differences in proenkephalin expression were observed in the bed nucleus of the stria terminalis, lateral septum, periventricular nucleus, and paraventricular nucleus. No differences were observed between treatments in seven other regions examined. We conclude that testosterone and season regulate proenkephalin mRNA levels in the preoptic area/hypothalamus in the ram in a region-specific manner.

Animals↗

PubMed1988

The effect of testosterone therapy on spontaneous growth hormone secretion in boys with constitutional delay.

Testosterone treatment is known to improve growth hormone (GH) secretion in boys with constitutional delay (CD). To determine whether spontaneous GH secretion is normal after treatment, we assessed GH secretion before and after a four- to five-month course of testosterone enanthate in eight adolescents with CD. Before testosterone therapy, the mean (+/- 1 SD) 24-hour integrated concentration of GH (IC-GH) by constant blood withdrawal technique was 1.7 +/- 1.0 micrograms/L (normal range for age, 3.2 to 11.5 micrograms/L), and the IC-testosterone was 1.8 +/- 2.7 nmol/L. Two patients restudied during treatment had normal IC-GH values. After testosterone treatment, the mean IC-GH of the entire group was 3.3 +/- 2.6 micrograms/L, and the IC-testosterone was 6.5 +/- 5.3 nmol/L. Five of eight patients had IC-GH values that were again subnormal. A subnormal IC-GH associated with CD may persist after testosterone therapy is discontinued. Deficiency of spontaneous GH secretion may contribute to short stature and slower growth rates in this patient group. Whether GH therapy in these patients would have a beneficial effect on final height is unknown.

Child↗

PubMed2000

A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms.

BACKGROUND: The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms (diminished libido, depressed mood, low energy, and depleted muscle mass) in men with symptomatic human immunodeficiency virus illness. METHODS: Seventy-four patients were enrolled in a double-blind, placebo-controlled 6-week trial with bi-weekly testosterone injections, followed by 12 weeks of open-label maintenance treatment. Major outcome measures were Clinical Global Impressions Scale ratings for libido, mood, energy, and erectile function; Hamilton Depression Rating Scale scores, and Chalder Fatigue Scale scores. Body composition changes were assessed with bioelectric impedance analysis. RESULTS: Seventy men completed the 6-week trial. Response rates, defined as much or very much improved libido, were 74% (28/38) for patients randomized to testosterone, and 19% (6/32) for placebo-treated patients (P<.001). Of the 62 completers with fatigue at baseline, 59% (20/34) receiving testosterone and 25% (7/28) receiving placebo reported improved energy (P<.01). Among the 26 completers with an Axis I depressive disorder at baseline, 58% of the testosterone-treated patients reported improved mood compared with 14% of placebo-treated patients (Fisher exact test = .08). With testosterone treatment, average increase in muscle mass over 12 weeks was 1.6 kg for the whole group, and 2.2 kg for the 14 men with wasting at baseline. Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks. CONCLUSION: Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness, restoring libido and energy, alleviating depressed mood, and increasing muscle mass.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Oral androstenedione administration and serum testosterone concentrations in young men.

CONTEXT: Androstenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown. OBJECTIVE: To determine if oral administration of androstenedione increases serum testosterone levels in healthy men. DESIGN: Open-label randomized controlled trial conducted between October 1998 and April 1999. SETTING: General clinical research center of a tertiary-care, university-affiliated hospital. PARTICIPANTS: Forty-two healthy men aged 20 to 40 years. INTERVENTION: Subjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days. MAIN OUTCOME MEASURES: Changes in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups. RESULTS: Mean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were -2% (7%), -4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P<.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids. CONCLUSIONS: Our data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men.

Administration, Oral↗